Guidelines

Patients on immunosuppressive or immunomodulatory therapy should receive a third dose of either the Pfizer-BioNTech COVID-19 vaccine or the Moderna COVID-19 vaccine at least 28 days after the second dose of either of these two mRNA vaccines, according to updated recommendations from the American College of Rheumatology.

Mongkolchon Akesin/Getty Images

The update follows the Centers for Disease Control and Prevention’s recommendation that certain immunocompromised patients receive a third dose of an mRNA vaccine to reduce their risk of contracting COVID-19.

Individuals receiving the Pfizer vaccine must be aged 12 years and older, while those receiving the Moderna vaccine must be 18 years and older, the ACR emphasized.

“These statements were based upon a dearth of high-quality data and are not intended to replace clinical judgment,” the authors wrote. “Modifications made to treatment plans, particularly in complex rheumatic disease patients, are highly disease, patient, geography, and time specific and, therefore, must be individualized as part of a shared decision-making process.”

The task force recommended using the same mRNA vaccine booster as the patient received for their initial two-dose series when possible, but notes that either mRNA vaccine is acceptable, and recommends the mRNA vaccine for patients who have yet to receive any vaccine because of the availability of the booster. The task force emphasized that they achieved no consensus on recommending a booster mRNA vaccine to patients who received a single dose of Johnson & Johnson vaccine because the safety data are uncertain.

The updated guidance also identifies the Food and Drug Administration’s emergency use authorization in August for the use of REGEN-COV monoclonal antibody treatment for emergency postexposure prophylaxis for COVID-19 in adults and adolescents aged 12 years and older who weigh at least 40 kg and are at increased risk for severe COVID-19, which includes patients receiving immunosuppressive or immunomodulatory therapies other than hydroxychloroquine. Patients who have been exposed to an individual with COVID-19 should discuss this treatment with their health care provider as an added precaution; however, the guidance emphasized that the prophylactic treatment is not a substitute for COVID-19 vaccination.

The recommendations advise clinicians to counsel their patients to refrain from taking certain immunomodulatory or immunosuppressive medications for 1-2 weeks after booster vaccination if disease activity allows, with the exception of glucocorticoids and anticytokines such as tumor necrosis factor inhibitors and others including interleukin-17, IL-12/23, IL-23, IL-1R, IL-6R antagonists, for which the task force did not achieve a consensus recommendation.

The guidance notes that patients on rituximab or other anti-CD20 medications “should discuss the optimal timing [of the booster] with their rheumatology provider” and that some practitioners measure CD19 B cells as a tool with which to time the booster and subsequent rituximab dosing. For those who elect to dose without such information, or for whom such measurement is not available or feasible, provide the booster 2-4 weeks before next anticipated rituximab dose (e.g., at month 5.0 or 5.5 for patients on an every-6-month rituximab dosing schedule).”

There was strong consensus from the task force that health care providers “should not routinely order any lab testing (e.g., antibody tests for IgM and/or IgG to spike or nucleocapsid proteins) to assess immunity to COVID-19 post vaccination, nor to assess the need for vaccination in a yet-unvaccinated person.”

“The updated information from the ACR addresses not only booster vaccination but also other important and practical issues facing rheumatology providers and their patients related to the pandemic,” said task force chair Jeffrey R. Curtis, MD, of the University of Alabama at Birmingham, in an ACR statement announcing the updates.

“Although the guidance is issued in light of the best evidence available, the science regarding COVID-19 vaccination as it affects the practice of rheumatology is undergoing rapid evolution,” he noted. “We need direct evidence such as that from randomized trials to inform the best practices of what we can do to protect our patients from SARS-CoV-2.”

The update retains the current recommendations that rheumatology patients follow all public health guidelines regarding physical distancing and other preventive measures following vaccination, but the task force did not recommend exceeding current public health guidance. “The appropriateness for continued preventive measures (e.g., masking, physical distancing) should be discussed with patients as their rheumatology providers deem appropriate,” they wrote.

The full updated version of the ACR’s COVID-19 Vaccine Clinical Guidance for Patients with Rheumatic and Musculoskeletal Diseases will be published in Arthritis & Rheumatology. The summary was developed by the ACR COVID-19 Vaccine Clinical Guidance Task Force, which included 9 rheumatologists, 2 infectious disease specialists, and 2 public health experts with current or past employment history with the CDC.

The ACR encourages clinicians with questions or concerns to email [email protected] for support.

Patients on immunosuppressive or immunomodulatory therapy should receive a third dose of either the Pfizer-BioNTech COVID-19 vaccine or the Moderna COVID-19 vaccine at least 28 days after the second dose of either of these two mRNA vaccines, according to updated recommendations from the American College of Rheumatology.

Mongkolchon Akesin/Getty Images

The update follows the Centers for Disease Control and Prevention’s recommendation that certain immunocompromised patients receive a third dose of an mRNA vaccine to reduce their risk of contracting COVID-19.

Individuals receiving the Pfizer vaccine must be aged 12 years and older, while those receiving the Moderna vaccine must be 18 years and older, the ACR emphasized.

“These statements were based upon a dearth of high-quality data and are not intended to replace clinical judgment,” the authors wrote. “Modifications made to treatment plans, particularly in complex rheumatic disease patients, are highly disease, patient, geography, and time specific and, therefore, must be individualized as part of a shared decision-making process.”

The task force recommended using the same mRNA vaccine booster as the patient received for their initial two-dose series when possible, but notes that either mRNA vaccine is acceptable, and recommends the mRNA vaccine for patients who have yet to receive any vaccine because of the availability of the booster. The task force emphasized that they achieved no consensus on recommending a booster mRNA vaccine to patients who received a single dose of Johnson & Johnson vaccine because the safety data are uncertain.

The updated guidance also identifies the Food and Drug Administration’s emergency use authorization in August for the use of REGEN-COV monoclonal antibody treatment for emergency postexposure prophylaxis for COVID-19 in adults and adolescents aged 12 years and older who weigh at least 40 kg and are at increased risk for severe COVID-19, which includes patients receiving immunosuppressive or immunomodulatory therapies other than hydroxychloroquine. Patients who have been exposed to an individual with COVID-19 should discuss this treatment with their health care provider as an added precaution; however, the guidance emphasized that the prophylactic treatment is not a substitute for COVID-19 vaccination.

The recommendations advise clinicians to counsel their patients to refrain from taking certain immunomodulatory or immunosuppressive medications for 1-2 weeks after booster vaccination if disease activity allows, with the exception of glucocorticoids and anticytokines such as tumor necrosis factor inhibitors and others including interleukin-17, IL-12/23, IL-23, IL-1R, IL-6R antagonists, for which the task force did not achieve a consensus recommendation.

The guidance notes that patients on rituximab or other anti-CD20 medications “should discuss the optimal timing [of the booster] with their rheumatology provider” and that some practitioners measure CD19 B cells as a tool with which to time the booster and subsequent rituximab dosing. For those who elect to dose without such information, or for whom such measurement is not available or feasible, provide the booster 2-4 weeks before next anticipated rituximab dose (e.g., at month 5.0 or 5.5 for patients on an every-6-month rituximab dosing schedule).”

There was strong consensus from the task force that health care providers “should not routinely order any lab testing (e.g., antibody tests for IgM and/or IgG to spike or nucleocapsid proteins) to assess immunity to COVID-19 post vaccination, nor to assess the need for vaccination in a yet-unvaccinated person.”

“The updated information from the ACR addresses not only booster vaccination but also other important and practical issues facing rheumatology providers and their patients related to the pandemic,” said task force chair Jeffrey R. Curtis, MD, of the University of Alabama at Birmingham, in an ACR statement announcing the updates.

“Although the guidance is issued in light of the best evidence available, the science regarding COVID-19 vaccination as it affects the practice of rheumatology is undergoing rapid evolution,” he noted. “We need direct evidence such as that from randomized trials to inform the best practices of what we can do to protect our patients from SARS-CoV-2.”

The update retains the current recommendations that rheumatology patients follow all public health guidelines regarding physical distancing and other preventive measures following vaccination, but the task force did not recommend exceeding current public health guidance. “The appropriateness for continued preventive measures (e.g., masking, physical distancing) should be discussed with patients as their rheumatology providers deem appropriate,” they wrote.

The full updated version of the ACR’s COVID-19 Vaccine Clinical Guidance for Patients with Rheumatic and Musculoskeletal Diseases will be published in Arthritis & Rheumatology. The summary was developed by the ACR COVID-19 Vaccine Clinical Guidance Task Force, which included 9 rheumatologists, 2 infectious disease specialists, and 2 public health experts with current or past employment history with the CDC.

The ACR encourages clinicians with questions or concerns to email [email protected] for support.

Patients on immunosuppressive or immunomodulatory therapy should receive a third dose of either the Pfizer-BioNTech COVID-19 vaccine or the Moderna COVID-19 vaccine at least 28 days after the second dose of either of these two mRNA vaccines, according to updated recommendations from the American College of Rheumatology.

Mongkolchon Akesin/Getty Images

The update follows the Centers for Disease Control and Prevention’s recommendation that certain immunocompromised patients receive a third dose of an mRNA vaccine to reduce their risk of contracting COVID-19.

Individuals receiving the Pfizer vaccine must be aged 12 years and older, while those receiving the Moderna vaccine must be 18 years and older, the ACR emphasized.

“These statements were based upon a dearth of high-quality data and are not intended to replace clinical judgment,” the authors wrote. “Modifications made to treatment plans, particularly in complex rheumatic disease patients, are highly disease, patient, geography, and time specific and, therefore, must be individualized as part of a shared decision-making process.”

The task force recommended using the same mRNA vaccine booster as the patient received for their initial two-dose series when possible, but notes that either mRNA vaccine is acceptable, and recommends the mRNA vaccine for patients who have yet to receive any vaccine because of the availability of the booster. The task force emphasized that they achieved no consensus on recommending a booster mRNA vaccine to patients who received a single dose of Johnson & Johnson vaccine because the safety data are uncertain.

The updated guidance also identifies the Food and Drug Administration’s emergency use authorization in August for the use of REGEN-COV monoclonal antibody treatment for emergency postexposure prophylaxis for COVID-19 in adults and adolescents aged 12 years and older who weigh at least 40 kg and are at increased risk for severe COVID-19, which includes patients receiving immunosuppressive or immunomodulatory therapies other than hydroxychloroquine. Patients who have been exposed to an individual with COVID-19 should discuss this treatment with their health care provider as an added precaution; however, the guidance emphasized that the prophylactic treatment is not a substitute for COVID-19 vaccination.

The recommendations advise clinicians to counsel their patients to refrain from taking certain immunomodulatory or immunosuppressive medications for 1-2 weeks after booster vaccination if disease activity allows, with the exception of glucocorticoids and anticytokines such as tumor necrosis factor inhibitors and others including interleukin-17, IL-12/23, IL-23, IL-1R, IL-6R antagonists, for which the task force did not achieve a consensus recommendation.

The guidance notes that patients on rituximab or other anti-CD20 medications “should discuss the optimal timing [of the booster] with their rheumatology provider” and that some practitioners measure CD19 B cells as a tool with which to time the booster and subsequent rituximab dosing. For those who elect to dose without such information, or for whom such measurement is not available or feasible, provide the booster 2-4 weeks before next anticipated rituximab dose (e.g., at month 5.0 or 5.5 for patients on an every-6-month rituximab dosing schedule).”

There was strong consensus from the task force that health care providers “should not routinely order any lab testing (e.g., antibody tests for IgM and/or IgG to spike or nucleocapsid proteins) to assess immunity to COVID-19 post vaccination, nor to assess the need for vaccination in a yet-unvaccinated person.”

“The updated information from the ACR addresses not only booster vaccination but also other important and practical issues facing rheumatology providers and their patients related to the pandemic,” said task force chair Jeffrey R. Curtis, MD, of the University of Alabama at Birmingham, in an ACR statement announcing the updates.

“Although the guidance is issued in light of the best evidence available, the science regarding COVID-19 vaccination as it affects the practice of rheumatology is undergoing rapid evolution,” he noted. “We need direct evidence such as that from randomized trials to inform the best practices of what we can do to protect our patients from SARS-CoV-2.”

The update retains the current recommendations that rheumatology patients follow all public health guidelines regarding physical distancing and other preventive measures following vaccination, but the task force did not recommend exceeding current public health guidance. “The appropriateness for continued preventive measures (e.g., masking, physical distancing) should be discussed with patients as their rheumatology providers deem appropriate,” they wrote.

The full updated version of the ACR’s COVID-19 Vaccine Clinical Guidance for Patients with Rheumatic and Musculoskeletal Diseases will be published in Arthritis & Rheumatology. The summary was developed by the ACR COVID-19 Vaccine Clinical Guidance Task Force, which included 9 rheumatologists, 2 infectious disease specialists, and 2 public health experts with current or past employment history with the CDC.

The ACR encourages clinicians with questions or concerns to email [email protected] for support.

New consensus recommendations address diagnosis and management of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), with advice that may also be helpful for patients with lingering symptoms following acute COVID-19 infection.

VioletaStoimenova/Getty Images

The document was published online Aug. 25, 2021, in the Mayo Clinic Proceedings by the 23-member U.S. ME/CFS Clinician Coalition, headed by Lucinda Bateman, MD, of the Bateman Horne Center of Excellence, Salt Lake City. The document is the culmination of work that began with a summit held at the center in March 2018.

The target audience is both generalist and specialist health care providers. While ME/CFS is estimated to affect up to 2.5 million Americans, more than 90% are either undiagnosed or misdiagnosed with other conditions such as depression. And those who are diagnosed often receive inappropriate, outdated treatments such as psychotherapy and exercise prescriptions.

“Despite myalgic encephalomyelitis/chronic fatigue syndrome affecting millions of people worldwide, many clinicians lack the knowledge to appropriately diagnose or manage ME/CFS. Unfortunately, clinical guidance has been scarce, obsolete, or potentially harmful,” Dr. Bateman and colleagues wrote.

The urgency of appropriate recognition and management of ME/CFS has increased as growing numbers of people are exhibiting signs and symptoms of ME/CFS following acute COVID-19 infection. This isn’t surprising because the illness has long been linked to other infections, including Epstein-Barr virus, the authors noted.

The document covers the epidemiology, impact, and prognosis of ME/CFS, as well as etiology and pathophysiology. “Scientific studies demonstrate multiple dysfunctional organ systems, including neuro, immune, and metabolic, in ME/CFS. These findings are not explained merely by deconditioning,” document coauthor Lily Chu, MD, an independent consultant in Burlingame, Calif., said in an interview.

The document reviews the 2015 U.S. Institute of Medicine (now Academy of Medicine) diagnostic criteria that are now also recommended by the Centers for Disease Control and Prevention. They are based on four main symptoms: substantial reduction or impairment in the ability to engage in preillness levels of occupational, educational, social or personal activities for longer than 6 months; postexertional malaise, a worsening of all current symptoms, that patients often describe as a “crash”; unrefreshing sleep; and cognitive impairment and/or orthostatic intolerance.

“The new diagnostic criteria focusing on the key symptom of postexertional malaise rather than chronic fatigue, which is common in many conditions, may make the diagnostic process quicker and more accurate. Diagnosis now is both an inclusionary and not just exclusionary process, so it’s not necessary to eliminate all causes of fatigue. Diagnose patients who fit the criteria and be alert for it in people with persistent symptoms post COVID,” Dr. Chu said.

The document provides advice for taking a clinical history to obtain the information necessary for making the diagnosis, including use of laboratory testing to rule out other conditions. Physical exams, while they may not reveal specific abnormalities, may help in identifying comorbidities and ruling out alternative diagnoses.

A long list of nonpharmacologic and pharmacologic treatment and management approaches is offered for each of the individual core and common ME/CFS symptoms, including postexertional malaise, orthostatic intolerance, sleep issues, cognitive dysfunction and fatigue, immune dysfunction, pain, and gastrointestinal issues.

The document recommends against using the “outdated standard of care” cognitive-behavioral therapy and graded exercise therapy as primary treatments for the illness. Instead, the authors recommend teaching patients “pacing,” an individualized approach to energy conservation aimed at minimizing the frequency, duration, and severity of postexertional malaise.

Clinicians are also advised to assess patients’ daily living needs and provide support, including acquiring handicap placards, work or school accommodations, and disability benefits.

“There are things clinicians can do now to help patients even without a disease-modifying treatment. These are actions they are already familiar with and carry out for people with other chronic diseases, which often have limited treatment options as well. Don’t underestimate the importance and value of supportive care for patients.” Dr. Chu said.

The recommendations are based primarily on clinical expertise because there are very few randomized trials, and much of the evidence from other types of trials has been flawed, document coauthor Anthony L. Komaroff, MD, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said in an interview.

“The sad reality is there aren’t very many large randomized clinical trials with this illness and so what a group of very experienced clinicians did was to gather their collective experience and report it as that. It’s largely uncontrolled experience, but from people who have seen a lot of patients, for what it’s worth to the medical community.”

Dr. Komaroff also advised that clinicians watch out for ME/CFS in patients with long COVID. “If we find that those called long COVID meet ME/CFS criteria, the reason for knowing that is that there are already some treatments that according to experienced clinicians are helpful for ME/CFS, and it would be perfectly appropriate to try some of them in long COVID, particularly the ones that have minimal adverse reactions.”

The guidelines project was supported by the Open Medicine Foundation. Dr. Komaroff reported receiving personal fees from Serimmune outside the submitted work. Dr. Chu has no disclosures.

New consensus recommendations address diagnosis and management of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), with advice that may also be helpful for patients with lingering symptoms following acute COVID-19 infection.

VioletaStoimenova/Getty Images

The document was published online Aug. 25, 2021, in the Mayo Clinic Proceedings by the 23-member U.S. ME/CFS Clinician Coalition, headed by Lucinda Bateman, MD, of the Bateman Horne Center of Excellence, Salt Lake City. The document is the culmination of work that began with a summit held at the center in March 2018.

The target audience is both generalist and specialist health care providers. While ME/CFS is estimated to affect up to 2.5 million Americans, more than 90% are either undiagnosed or misdiagnosed with other conditions such as depression. And those who are diagnosed often receive inappropriate, outdated treatments such as psychotherapy and exercise prescriptions.

“Despite myalgic encephalomyelitis/chronic fatigue syndrome affecting millions of people worldwide, many clinicians lack the knowledge to appropriately diagnose or manage ME/CFS. Unfortunately, clinical guidance has been scarce, obsolete, or potentially harmful,” Dr. Bateman and colleagues wrote.

The urgency of appropriate recognition and management of ME/CFS has increased as growing numbers of people are exhibiting signs and symptoms of ME/CFS following acute COVID-19 infection. This isn’t surprising because the illness has long been linked to other infections, including Epstein-Barr virus, the authors noted.

The document covers the epidemiology, impact, and prognosis of ME/CFS, as well as etiology and pathophysiology. “Scientific studies demonstrate multiple dysfunctional organ systems, including neuro, immune, and metabolic, in ME/CFS. These findings are not explained merely by deconditioning,” document coauthor Lily Chu, MD, an independent consultant in Burlingame, Calif., said in an interview.

The document reviews the 2015 U.S. Institute of Medicine (now Academy of Medicine) diagnostic criteria that are now also recommended by the Centers for Disease Control and Prevention. They are based on four main symptoms: substantial reduction or impairment in the ability to engage in preillness levels of occupational, educational, social or personal activities for longer than 6 months; postexertional malaise, a worsening of all current symptoms, that patients often describe as a “crash”; unrefreshing sleep; and cognitive impairment and/or orthostatic intolerance.

“The new diagnostic criteria focusing on the key symptom of postexertional malaise rather than chronic fatigue, which is common in many conditions, may make the diagnostic process quicker and more accurate. Diagnosis now is both an inclusionary and not just exclusionary process, so it’s not necessary to eliminate all causes of fatigue. Diagnose patients who fit the criteria and be alert for it in people with persistent symptoms post COVID,” Dr. Chu said.

The document provides advice for taking a clinical history to obtain the information necessary for making the diagnosis, including use of laboratory testing to rule out other conditions. Physical exams, while they may not reveal specific abnormalities, may help in identifying comorbidities and ruling out alternative diagnoses.

A long list of nonpharmacologic and pharmacologic treatment and management approaches is offered for each of the individual core and common ME/CFS symptoms, including postexertional malaise, orthostatic intolerance, sleep issues, cognitive dysfunction and fatigue, immune dysfunction, pain, and gastrointestinal issues.

The document recommends against using the “outdated standard of care” cognitive-behavioral therapy and graded exercise therapy as primary treatments for the illness. Instead, the authors recommend teaching patients “pacing,” an individualized approach to energy conservation aimed at minimizing the frequency, duration, and severity of postexertional malaise.

Clinicians are also advised to assess patients’ daily living needs and provide support, including acquiring handicap placards, work or school accommodations, and disability benefits.

“There are things clinicians can do now to help patients even without a disease-modifying treatment. These are actions they are already familiar with and carry out for people with other chronic diseases, which often have limited treatment options as well. Don’t underestimate the importance and value of supportive care for patients.” Dr. Chu said.

The recommendations are based primarily on clinical expertise because there are very few randomized trials, and much of the evidence from other types of trials has been flawed, document coauthor Anthony L. Komaroff, MD, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said in an interview.

“The sad reality is there aren’t very many large randomized clinical trials with this illness and so what a group of very experienced clinicians did was to gather their collective experience and report it as that. It’s largely uncontrolled experience, but from people who have seen a lot of patients, for what it’s worth to the medical community.”

Dr. Komaroff also advised that clinicians watch out for ME/CFS in patients with long COVID. “If we find that those called long COVID meet ME/CFS criteria, the reason for knowing that is that there are already some treatments that according to experienced clinicians are helpful for ME/CFS, and it would be perfectly appropriate to try some of them in long COVID, particularly the ones that have minimal adverse reactions.”

The guidelines project was supported by the Open Medicine Foundation. Dr. Komaroff reported receiving personal fees from Serimmune outside the submitted work. Dr. Chu has no disclosures.

New consensus recommendations address diagnosis and management of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), with advice that may also be helpful for patients with lingering symptoms following acute COVID-19 infection.

VioletaStoimenova/Getty Images

The document was published online Aug. 25, 2021, in the Mayo Clinic Proceedings by the 23-member U.S. ME/CFS Clinician Coalition, headed by Lucinda Bateman, MD, of the Bateman Horne Center of Excellence, Salt Lake City. The document is the culmination of work that began with a summit held at the center in March 2018.

The target audience is both generalist and specialist health care providers. While ME/CFS is estimated to affect up to 2.5 million Americans, more than 90% are either undiagnosed or misdiagnosed with other conditions such as depression. And those who are diagnosed often receive inappropriate, outdated treatments such as psychotherapy and exercise prescriptions.

“Despite myalgic encephalomyelitis/chronic fatigue syndrome affecting millions of people worldwide, many clinicians lack the knowledge to appropriately diagnose or manage ME/CFS. Unfortunately, clinical guidance has been scarce, obsolete, or potentially harmful,” Dr. Bateman and colleagues wrote.

The urgency of appropriate recognition and management of ME/CFS has increased as growing numbers of people are exhibiting signs and symptoms of ME/CFS following acute COVID-19 infection. This isn’t surprising because the illness has long been linked to other infections, including Epstein-Barr virus, the authors noted.

The document covers the epidemiology, impact, and prognosis of ME/CFS, as well as etiology and pathophysiology. “Scientific studies demonstrate multiple dysfunctional organ systems, including neuro, immune, and metabolic, in ME/CFS. These findings are not explained merely by deconditioning,” document coauthor Lily Chu, MD, an independent consultant in Burlingame, Calif., said in an interview.

The document reviews the 2015 U.S. Institute of Medicine (now Academy of Medicine) diagnostic criteria that are now also recommended by the Centers for Disease Control and Prevention. They are based on four main symptoms: substantial reduction or impairment in the ability to engage in preillness levels of occupational, educational, social or personal activities for longer than 6 months; postexertional malaise, a worsening of all current symptoms, that patients often describe as a “crash”; unrefreshing sleep; and cognitive impairment and/or orthostatic intolerance.

“The new diagnostic criteria focusing on the key symptom of postexertional malaise rather than chronic fatigue, which is common in many conditions, may make the diagnostic process quicker and more accurate. Diagnosis now is both an inclusionary and not just exclusionary process, so it’s not necessary to eliminate all causes of fatigue. Diagnose patients who fit the criteria and be alert for it in people with persistent symptoms post COVID,” Dr. Chu said.

The document provides advice for taking a clinical history to obtain the information necessary for making the diagnosis, including use of laboratory testing to rule out other conditions. Physical exams, while they may not reveal specific abnormalities, may help in identifying comorbidities and ruling out alternative diagnoses.

A long list of nonpharmacologic and pharmacologic treatment and management approaches is offered for each of the individual core and common ME/CFS symptoms, including postexertional malaise, orthostatic intolerance, sleep issues, cognitive dysfunction and fatigue, immune dysfunction, pain, and gastrointestinal issues.

The document recommends against using the “outdated standard of care” cognitive-behavioral therapy and graded exercise therapy as primary treatments for the illness. Instead, the authors recommend teaching patients “pacing,” an individualized approach to energy conservation aimed at minimizing the frequency, duration, and severity of postexertional malaise.

Clinicians are also advised to assess patients’ daily living needs and provide support, including acquiring handicap placards, work or school accommodations, and disability benefits.

“There are things clinicians can do now to help patients even without a disease-modifying treatment. These are actions they are already familiar with and carry out for people with other chronic diseases, which often have limited treatment options as well. Don’t underestimate the importance and value of supportive care for patients.” Dr. Chu said.

The recommendations are based primarily on clinical expertise because there are very few randomized trials, and much of the evidence from other types of trials has been flawed, document coauthor Anthony L. Komaroff, MD, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said in an interview.

“The sad reality is there aren’t very many large randomized clinical trials with this illness and so what a group of very experienced clinicians did was to gather their collective experience and report it as that. It’s largely uncontrolled experience, but from people who have seen a lot of patients, for what it’s worth to the medical community.”

Dr. Komaroff also advised that clinicians watch out for ME/CFS in patients with long COVID. “If we find that those called long COVID meet ME/CFS criteria, the reason for knowing that is that there are already some treatments that according to experienced clinicians are helpful for ME/CFS, and it would be perfectly appropriate to try some of them in long COVID, particularly the ones that have minimal adverse reactions.”

The guidelines project was supported by the Open Medicine Foundation. Dr. Komaroff reported receiving personal fees from Serimmune outside the submitted work. Dr. Chu has no disclosures.

There will be so much more to the annual congress of the European Society of Cardiology, which begins Aug. 27 with an all-virtual format, than detailed primary results of EMPEROR-Preserved, a trial that could mark a turning point for heart failure (HF) medical therapy.

Also among the featured Hot Line and Late-Breaking Science sessions are – along with many other studies – explorations of arrhythmia management (ablation or guided by loop recorder); secondary prevention, including by vaccination; oral anticoagulation, notably after transcatheter valve procedures; and colchicine or thrombosis prophylaxis in hospitalized patients with COVID-19.

There will even be a head-to-head comparison of two long-familiar left atrial appendage (LAA) occluders, and a population-based, randomized trial of sodium restriction through wide-scale use of a potassium-based salt substitute.

The congress will also introduce four guideline documents at sessions throughout the Congress, one on each day. They cover new and modified recommendations for heart failure; pacing, including cardiac resynchronization therapy (CRT); cardiovascular (CV) disease prevention; and, with cosponsorship from the European Association for Cardio-Thoracic Surgery, valvular heart disease.
 

The virtues of virtual

That next year’s Congress is slated for Aug. 27-30 in Barcelona should be welcome news for anyone whose “what if” curiosity about all-virtual conferences has already been satisfied. But with experience comes wisdom, as the medical societies have learned that online scientific meetings have some winning qualities that may be worth keeping, as least for a while.

“I think there is no doubt that the digital format will continue, for several reasons. One is that this pandemic is not over,” ESC Congress program committee chair Stephan Windecker, MD, Bern (Switzerland) University Hospital, , told this news organization. “As long as it is not over, the digital format is here to stay.”

But it also appears that people who haven’t been able to attend the congress in person are keen to log in and engage online, Dr. Windecker said. The 2020 all-virtual conference drew a much younger pool of registrants, on average, than did the live conferences before the pandemic.

“I think that’s an indication of people that may be in training, in early stages of their career, or they don’t have the support from departments or from their practice, or other financial means.” But they are able to participate via computer, tablet, or smartphone, he said.

“Another advantage is that the recorded content can be replayed at the convenience of whoever wants to consume it at a later point in time,” he added. “Those are just some examples why the digital format is likely to stay,” on its own or in a new age of hybrid meetings.  
 

New and updated guidelines

Leading off the guideline series is the document on diagnosis and treatment of acute and chronic HF, which leveraged the past few busy years of HF clinical trials to arrive at a number of new recommendations and strengthened level-of-evidence ratings. It covers both drug and device therapy of HF with reduced ejection fraction (HFrEF) and acute decompensated HF, and tweaks and further enshrines the concept of HF with mildly reduced ejection fraction (HFmrEF).

Several updated recommendations for both long-used and novel medications, notably the sodium-glucose cotransporter 2 inhibitors, will be included because of the recently appreciated evidence-based impact in HFrEF, Dr. Windecker noted.

“I think it will be particularly interesting to look for the SGLT2 inhibitors as not a completely new class of drugs, but certainly one where there has been a lot of new evidence, to look at how those drugs will be integrated in the overall care pathway.”

A top-line preview of the new HF guideline limited to drug therapy, presented at July’s Heart Failure Association of the European Society of Cardiology (ESC-HFA), provided a simple answer to a common question in the new, bountiful age of HFrEF medications: Which meds, initiated in what order?

As it happens, the new recommendation for first-line HFrEF drug therapy is not a silver bullet, but a shotgun – prompt initiation of at least four meds, one from each of four drug classes: renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRA), and SGLT2 inhibitors. Each class, as described in the document, is to be started as soon as safely feasible, in a sequence deemed appropriate for each individual patient.
 

Spotlight on EMPEROR-Preserved

The world already knows that the trial, which tested the SGLT2 inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) on top of standard therapy, “met” its primary endpoint in almost 6,000 patients with HF with preserved ejection fraction (HFpEF), who included some with HFmrEF by more contemporary definitions.

That means patients in EMPEROR-Preserved assigned to take empagliflozin showed significantly fewer events that made up the study’s primary endpoint, a composite of CV death or HF hospitalization. It appears to be the first clearly significant overall medical therapy benefit for a clinical primary endpoint in a major randomized HFpEF drug trial.

And that, pending fuller presentation of trial results at the Congress on Aug. 27, could be a huge deal for the half of HF patients with left ventricular ejection fractions (LVEF) higher than the HFrEF range.

Those early top-line results weren’t a decisive bombshell for a field now filled with hope for a practice-changing empagliflozin outcome in EMPEROR-Preserved, which isn’t a certainty. They were more like the “boom” of a mortar launching a rocket of fireworks that may explode into a chrysanthemum or green comet or, sometimes, turn out to be no more than a dud. The promise of the early cursory results critically depends on further details.

“Provided there is a compelling benefit, this is what everyone has been waiting for in this condition for decades,” Mikhail N. Kosiborod, MD, director of cardiometabolic research at Saint Luke’s Mid-America Heart Institute, Kansas City, Mo., said.

“Already knowing that the trial met the primary endpoint is obviously very intriguing and encouraging,” he added. “But there are things we don’t know, such as: What is the magnitude of benefit? And whether that benefit, whatever the magnitude, is driven by reductions in both heart failure hospitalizations and cardiovascular death, or only one of the two.”

For example: “If we see an impressive benefit for reduction of hospitalizations, but not a significant reduction in death, that would still be a huge advance. That’s because, to date, we don’t have any drug for HFpEF that has convincingly demonstrated a compelling reduction in heart failure hospitalization or improvement in symptoms, function, or quality of life,” observed Dr. Kosiborod, who wasn’t part of EMPEROR-Preserved.

There have been “suggestions” from HFrEF trials that empagliflozin and dapagliflozin (Farxiga, AstraZeneca) “have very comparable effects on at least the endpoint of cardiovascular death or hospitalization for heart failure,” he said. “So, my expectation would be that whatever is observed in EMPEROR-Preserved is likely a class effect, as well.”

Following EMPEROR-Preserved on the agenda is EMPEROR-Pooled, a patient-level combined analysis of the EMPEROR series of trials that spans the range of HF, regardless of ejection fraction or diabetes status, primarily exploring the effects of empagliflozin on renal function.
 

Other offerings, Friday, Aug. 27

Scheduled immediately after EMPEROR-Preserved is a presentation on the SMART-MI trial, which should clarify whether management guided by continuous ambulatory monitoring is effective in patients considered at especially high arrhythmic risk. Entry called for recent myocardial infarction and an LVEF of 36%-50% with evidence of cardiac autonomic dysfunction.

The trial randomly assigned 400 such patients to be or not be implanted with a Reveal LINQ (Medtronic) loop recorder and followed them for up to 18 months, primarily for detection of potentially serious arrhythmic events. Endpoints that involved mortality, hospitalization or other clinical events were secondary.

In a time slot preceding both SMART-MI and EMPEROR-Preserved, the GUIDE-HF trial is following a projected 3,600 patients with HF implanted with a CardioMEMS HF System (Abbott) pulmonary artery (PA) pressure sensor to explore the its value for guiding management.

The trial’s three cohorts, followed for at least 12 months, include randomized sensor-monitored and control groups of patients with New York Heart Association class 2-4 symptoms, as well as a third observational set of patients in NYHA class 3. That’s the indication for which the CardioMEMS monitor gained approval in the United States in 2014 based on the 2011 CHAMPION trial, and which fared just as well in the 2017 CHAMPION Post-Approval Study.

The Friday Hot Lines also include Dal-GenE, which has entered about 6,000 patients with recent MI to test the once-abandoned cholesterol ester transfer protein (CETP) inhibitor dalcetrapib (DalCor) for any secondary-prevention benefits when used selectively. The trial’s hook: All its patients are confirmed to have the AA genotype of the rs1967309 variant in the ADCY9 gene, which has been associated with a pronounced clinical response to CETP inhibition.

Saturday, Aug. 28

The direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists in patients with nonvalvular atrial fibrillation (AFib). But whether DOACs are similarly preferable in the growing world population of people who have undergone transcatheter aortic valve replacement (TAVR or TAVI), an issue explored with variable results in the ATLANTIS and GALILEO trials, is far from settled.

The ENVISAGE-TAVI AF trial explored the question for the factor X inhibitor edoxaban (Savaysa, Lixiana, Daiichi-Sankyo) in 1,400 patients with AFib and a transfemoral TAVR in the previous 5 days, who were randomly assigned to the DOAC or standard management along with discretionary antiplatelet therapy. They’ve been followed for up to 3 years for a composite endpoint of clinical events – including death, MI, and stroke – and for major bleeding.

The day will also feature MASTER DAPT, a comparison of two dual-antiplatelet therapy (DAPT) regimens in an estimated 4,300 patients considered to be high-risk for bleeding who had received the sirolimus-eluting Ultimaster (Terumo) coronary stent, which has a bioresorbable polymer coating.

Investigators have randomly assigned patients to receive either very-short-duration DAPT, for about a month after stenting, followed by a P2Y12 inhibitor alone for up to a year after the procedure; or a more conventional regimen of a P2Y12 inhibitor for 6-12 months with aspirin maintained for a total of 12 months.

Later that day, investigators from the FIGARO-DKD trial will present their results based on 7,437 patients with type 2 diabetes and chronic kidney disease (CKD), a much fuller version than the top-line findings announced by sponsor Bayer 3 months ago.

Those top-line results suggested that patients assigned to receive the nonsteroidal nonselective mineralocorticoid receptor antagonist (MRA) finerenone (Kerendia) on top of standard care benefited with a drop in risk for the primary endpoint of CV death or nonfatal CV events.

Finerenone was recently approved in the United States for treating patients with both type 2 diabetes and CKD based on the published FIDELIO-DKD trial, which had seen less CKD progression and fewer CV events in such patients who took the novel MRA.

Although similar in design to FIGARO-DKD, FIDELIO-DKD had entered fewer patients with early-stage diabetic kidney disease (DKD). That led researchers to pool the two trials’ populations to create a cohort that spans the spectrum of DKD severity. An analysis of the pooled cohort, dubbed FIDELITY, is on the schedule after FIGARO-DKD.

After FIDELITY is the prospective APAF-CRT trial that is following a projected 1,830 patients with permanent, symptomatic AFib and a recent hospitalization for AFib or HF and who were not good candidates for standard ablation. They were assigned to receive either atrioventricular junctional ablation followed by CRT, with or without a defibrillation, on top of optimal meds – a so-called “ablate-and-pace” strategy – or an implantable cardioverter defibrillator with rate-control drug therapy.

The new analysis represents the trial’s second phase in which mortality was followed for 4 years as the primary endpoint, in contrast to the previously reported initial phase that followed the first 102 patients for 2 years for the composite primary endpoint of death, worsening HF, and HF hospitalization. The first phase had halted enrollment before reaching its planned target of 280 patients after an interim analysis showed a significant benefit for ablate and pace. 

Next up: DECAAF 2, a randomized assessment of whether catheter ablation for AFib guided by delayed gadolinium enhancement on MRI, a proxy for scar tissue, can be more effective than standard AFib ablation by pulmonary vein isolation alone. An estimated 900 patients with persistent AFib who had never before undergone ablation for the arrhythmia were randomly assigned to one strategy or the other and followed for AFib recurrence over 18 months.
 

Sunday, Aug. 29

The TOMAHAWK trial aimed to clarify the optimal timing of invasive coronary angiography for resuscitated patients with non–ST-segment elevation out-of-hospital cardiac arrest, a broad population in a setting for which there is little randomized-trial guidance. Investigators randomly assigned 558 such patients to undergo immediate invasive angiography or to direct intensive care unit admission for initial standard care with discretionary delayed angiography. Patients were followed for all-cause mortality, with other clinical events and neurologic outcomes as secondary endpoints.

Next on the schedule, the RIPCORD-2 trial randomly assigned 1,100 patients with stable known or suspected coronary artery disease (CAD) to undergo conventional angiography alone or with added direct pressure-wire measurement of fractional flow reserve to guide management decisions. Primary outcomes include health care costs and patient-reported quality of life at 1 year.

Slated for later that day, the Asymptomatic Carotid Surgery Trial-2 (ACST-2) has entered an estimated 3600 patients with a substantial carotid artery narrowing not associated with symptoms but for which either carotid endarterectomy (CEA) or carotid artery stenting (CAS) was considered anatomically feasible. There also must have been “substantial uncertainty” regarding the optimal procedure choice.

The trial, conducted in 40 countries primarily in Europe and North America and launched in 2008, randomly assigned the patients to undergo either CEA or CAS, in both cases with appropriate medical therapy, and followed them for periprocedural events and up to 10 years for strokes and stroke-related events.

The LOOP study, which is to directly follow ACST-2, has explored whether screening for AFib using the Medtronic Reveal LINQ monitor in older patients with non-AFib stroke risk factors – with oral anticoagulation prescribed for those who test positive – can lower their risk for stroke or systemic embolism. It randomly assigned 6,000 such patients to care guided by the loop recorder or to standard care.

On a somewhat larger scale, the Salt Substitute and Stroke Study (SSaSS) randomly assigned a total of 20,996 people in about 600 villages across northern China and Tibet to sodium-restriction intervention and control groups by village. All participants had a history of stroke or were aged at least 60 years with uncontrolled hypertension.

As described by the trial’s online portal, participants in villages assigned to the intervention group were given a supply of a low-sodium, potassium-supplementing salt substitute to replace their own salt supplies, along with education on the health benefits of sodium restriction. Participants in control villages continued their normal diets and, at the trial’s beginning, received “advice to reduce their salt intake.” All were required to own a telephone.

Clinical events, including strokes and hospitalizations throughout a 5-year follow-up, were tracked by phone calls made to all participants every 6 months and were documented at follow-up home visits.

Sunday is also to feature a Late-Breaking Trials session with a focus on COVID-19, which leads off with COLCOVID, a test of colchicine in patients hospitalized for suspected SARS-CoV-2 infection and in acute respiratory distress.

The 1,279 participants in Argentina were randomly assigned to receive or not receive the potent anti-inflammatory agent on top of antivirals and other standard management and followed for death or new need for mechanical ventilation. A successful outcome would contrast with the RECOVERY trial, which terminated a colchicine group of patients hospitalized with COVID-19 because of a lack of efficacy earlier this year.

COLCOVID is to be followed by the MICHELLE trial of rivaroxaban (Xarelto, Bayer/Janssen) prophylaxis, compared with no preventive oral anticoagulant, in 320 patients who, when hospitalized with COVID-19, had been on parenteral anticoagulants because of an elevated risk for venous thromboembolism. The trial, conducted in Brazil, called for postdischarge rivaroxaban at a once-daily dosage of 10 mg for about 1 month.

The session also includes a presentation called “Insights into the Effects of the COVID-19 Pandemic: Comprehensive Analysis from the GUIDE-HF Trial,” the primary outcomes of which will be reported on the first day of the Congress.

Following is a presentation on the PREPARE-IT study of icosapent ethyl (Vascepa, Amarin), given at high dosages intended to be anti-inflammatory, compared with placebo, in an estimated 4,000 adults. The trial has two groups: A prevention group of adults living and circulating in the community; and a treatment group of patients aged at least 40 years with confirmed symptomatic SARS-CoV-2 infection for whom the need for hospitalization isn’t clear.
 

Monday, Aug. 30

The final day of the Congress features a trial called Influenza Vaccination after Myocardial Infarction (IAMI), which has tested the secondary preventive effect of influenza vaccination by randomly assigning 2,571 patients to receive a standard vaccine or a saline placebo injection on one occasion.

Entry to the international trial called for a diagnosis of MI with or without ST-segment elevation, or stable CAD and age at least 75 years with other risk factors. The patients were followed for death, MI, stent thrombosis, and a slew of secondary endpoints over 12 months.

Monday offerings continue later in a time block leading off with the STEP trial, which has randomly assigned an estimated 8,000 patients at 40 centers in China who are 60 to 80 years of age with a systolic blood pressure of 140 to <190 mm Hg to be on standard guideline-based therapy or an intensive drug-management strategy.

The systolic BP goals are 130 to <150 mm Hg for standard care and 110 to <130 mm Hg for the intensive regimen. The composite primary endpoint includes death and clinical events related to acute coronary syndromes, HF, revascularization, and stroke.

Following on heels of STEP, the Amulet IDE trial – the first major randomized comparison of two transcatheter LAA closure devices – entered 1,878 patients with nonvalvular AFib who were considered high-risk for bleeding and stroke or systemic embolism.

They were randomly assigned in the noninferiority trial to receive either the AMPLATZER Amulet (Abbott Medical Devices) or the WATCHMAN (Boston Scientific) closure devices and were followed for safety and efficacy for up to 5 years.

Both LAA closure devices, intended to make patients with AFib less reliant on oral anticoagulation, are now available on both sides of the Atlantic – as well as many other countries – after the Amulet’s United States market approval on Aug. 16, based largely on the Amulet IDE trial.

Rounding out the final Hot Line set is one of the latest efforts to show the efficacy and safety of a very short DAPT period after coronary stenting in patients with acute coronary syndromes, the STOPDAPT-2 ACS trial.

The study assigned 3,008 patients in Japan to receive aspirin and clopidogrel for either 1 month or 1 year after implantation with an everolimus-eluting cobalt-chromium stent and followed them for up to 5 years for a composite of MI, CV death, stent thrombosis, stroke, and bleeding.

The trial follows the published STOPDAPT-2 trial that showed superiority for the 1-month DAPT regimen in a predominantly stable-CAD population treated with the same kind of stent.
 

Program structure and format

A total of 15 online channels are to be available in the morning, European time, their schedules running in parallel. Presentations often are prerecorded, but also include live sessions at 8:00 a.m. Central time and 12 p.m. CET (2:00 a.m. and 6:00 a.m. Eastern time) to liven up the channel offerings, Dr. Windecker observed, and to make them more immediate and potentially interactive.

Many of the parallel channels are devoted throughout the Congress to particular silos of cardiology; for example, arrhythmias and device therapy is on channel 3; CAD and acute care is on 5; HF is on 6; and preventive cardiology is on 9.

Other channels swing across different topics from day to day, such as channel 1, which covers COVID-19 topics on the first and third day of the meeting, “advances in science” on day 2, and “digital health, public health, health economics” on day 4.

The focus each day, starting at 2:00 p.m. CET (8:00 a.m. ET) and continuing into the evening in Europe, shifts over to the Prime Time live program, which features the Hot Line and guideline presentations and many of the live abstract presentations.

Dr. Kosiborod, not a researcher with the EMPEROR trials, is chair of the Dapagliflozin in Preserved Ejection Fraction Heart Failure ( PRESERVED-HF ) trial, which is scheduled for presentation at the September 2021 Heart Failure Society of American meeting.

A version of this article first appeared on Medscape.com.

There will be so much more to the annual congress of the European Society of Cardiology, which begins Aug. 27 with an all-virtual format, than detailed primary results of EMPEROR-Preserved, a trial that could mark a turning point for heart failure (HF) medical therapy.

Also among the featured Hot Line and Late-Breaking Science sessions are – along with many other studies – explorations of arrhythmia management (ablation or guided by loop recorder); secondary prevention, including by vaccination; oral anticoagulation, notably after transcatheter valve procedures; and colchicine or thrombosis prophylaxis in hospitalized patients with COVID-19.

There will even be a head-to-head comparison of two long-familiar left atrial appendage (LAA) occluders, and a population-based, randomized trial of sodium restriction through wide-scale use of a potassium-based salt substitute.

The congress will also introduce four guideline documents at sessions throughout the Congress, one on each day. They cover new and modified recommendations for heart failure; pacing, including cardiac resynchronization therapy (CRT); cardiovascular (CV) disease prevention; and, with cosponsorship from the European Association for Cardio-Thoracic Surgery, valvular heart disease.
 

The virtues of virtual

That next year’s Congress is slated for Aug. 27-30 in Barcelona should be welcome news for anyone whose “what if” curiosity about all-virtual conferences has already been satisfied. But with experience comes wisdom, as the medical societies have learned that online scientific meetings have some winning qualities that may be worth keeping, as least for a while.

“I think there is no doubt that the digital format will continue, for several reasons. One is that this pandemic is not over,” ESC Congress program committee chair Stephan Windecker, MD, Bern (Switzerland) University Hospital, , told this news organization. “As long as it is not over, the digital format is here to stay.”

But it also appears that people who haven’t been able to attend the congress in person are keen to log in and engage online, Dr. Windecker said. The 2020 all-virtual conference drew a much younger pool of registrants, on average, than did the live conferences before the pandemic.

“I think that’s an indication of people that may be in training, in early stages of their career, or they don’t have the support from departments or from their practice, or other financial means.” But they are able to participate via computer, tablet, or smartphone, he said.

“Another advantage is that the recorded content can be replayed at the convenience of whoever wants to consume it at a later point in time,” he added. “Those are just some examples why the digital format is likely to stay,” on its own or in a new age of hybrid meetings.  
 

New and updated guidelines

Leading off the guideline series is the document on diagnosis and treatment of acute and chronic HF, which leveraged the past few busy years of HF clinical trials to arrive at a number of new recommendations and strengthened level-of-evidence ratings. It covers both drug and device therapy of HF with reduced ejection fraction (HFrEF) and acute decompensated HF, and tweaks and further enshrines the concept of HF with mildly reduced ejection fraction (HFmrEF).

Several updated recommendations for both long-used and novel medications, notably the sodium-glucose cotransporter 2 inhibitors, will be included because of the recently appreciated evidence-based impact in HFrEF, Dr. Windecker noted.

“I think it will be particularly interesting to look for the SGLT2 inhibitors as not a completely new class of drugs, but certainly one where there has been a lot of new evidence, to look at how those drugs will be integrated in the overall care pathway.”

A top-line preview of the new HF guideline limited to drug therapy, presented at July’s Heart Failure Association of the European Society of Cardiology (ESC-HFA), provided a simple answer to a common question in the new, bountiful age of HFrEF medications: Which meds, initiated in what order?

As it happens, the new recommendation for first-line HFrEF drug therapy is not a silver bullet, but a shotgun – prompt initiation of at least four meds, one from each of four drug classes: renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRA), and SGLT2 inhibitors. Each class, as described in the document, is to be started as soon as safely feasible, in a sequence deemed appropriate for each individual patient.
 

Spotlight on EMPEROR-Preserved

The world already knows that the trial, which tested the SGLT2 inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) on top of standard therapy, “met” its primary endpoint in almost 6,000 patients with HF with preserved ejection fraction (HFpEF), who included some with HFmrEF by more contemporary definitions.

That means patients in EMPEROR-Preserved assigned to take empagliflozin showed significantly fewer events that made up the study’s primary endpoint, a composite of CV death or HF hospitalization. It appears to be the first clearly significant overall medical therapy benefit for a clinical primary endpoint in a major randomized HFpEF drug trial.

And that, pending fuller presentation of trial results at the Congress on Aug. 27, could be a huge deal for the half of HF patients with left ventricular ejection fractions (LVEF) higher than the HFrEF range.

Those early top-line results weren’t a decisive bombshell for a field now filled with hope for a practice-changing empagliflozin outcome in EMPEROR-Preserved, which isn’t a certainty. They were more like the “boom” of a mortar launching a rocket of fireworks that may explode into a chrysanthemum or green comet or, sometimes, turn out to be no more than a dud. The promise of the early cursory results critically depends on further details.

“Provided there is a compelling benefit, this is what everyone has been waiting for in this condition for decades,” Mikhail N. Kosiborod, MD, director of cardiometabolic research at Saint Luke’s Mid-America Heart Institute, Kansas City, Mo., said.

“Already knowing that the trial met the primary endpoint is obviously very intriguing and encouraging,” he added. “But there are things we don’t know, such as: What is the magnitude of benefit? And whether that benefit, whatever the magnitude, is driven by reductions in both heart failure hospitalizations and cardiovascular death, or only one of the two.”

For example: “If we see an impressive benefit for reduction of hospitalizations, but not a significant reduction in death, that would still be a huge advance. That’s because, to date, we don’t have any drug for HFpEF that has convincingly demonstrated a compelling reduction in heart failure hospitalization or improvement in symptoms, function, or quality of life,” observed Dr. Kosiborod, who wasn’t part of EMPEROR-Preserved.

There have been “suggestions” from HFrEF trials that empagliflozin and dapagliflozin (Farxiga, AstraZeneca) “have very comparable effects on at least the endpoint of cardiovascular death or hospitalization for heart failure,” he said. “So, my expectation would be that whatever is observed in EMPEROR-Preserved is likely a class effect, as well.”

Following EMPEROR-Preserved on the agenda is EMPEROR-Pooled, a patient-level combined analysis of the EMPEROR series of trials that spans the range of HF, regardless of ejection fraction or diabetes status, primarily exploring the effects of empagliflozin on renal function.
 

Other offerings, Friday, Aug. 27

Scheduled immediately after EMPEROR-Preserved is a presentation on the SMART-MI trial, which should clarify whether management guided by continuous ambulatory monitoring is effective in patients considered at especially high arrhythmic risk. Entry called for recent myocardial infarction and an LVEF of 36%-50% with evidence of cardiac autonomic dysfunction.

The trial randomly assigned 400 such patients to be or not be implanted with a Reveal LINQ (Medtronic) loop recorder and followed them for up to 18 months, primarily for detection of potentially serious arrhythmic events. Endpoints that involved mortality, hospitalization or other clinical events were secondary.

In a time slot preceding both SMART-MI and EMPEROR-Preserved, the GUIDE-HF trial is following a projected 3,600 patients with HF implanted with a CardioMEMS HF System (Abbott) pulmonary artery (PA) pressure sensor to explore the its value for guiding management.

The trial’s three cohorts, followed for at least 12 months, include randomized sensor-monitored and control groups of patients with New York Heart Association class 2-4 symptoms, as well as a third observational set of patients in NYHA class 3. That’s the indication for which the CardioMEMS monitor gained approval in the United States in 2014 based on the 2011 CHAMPION trial, and which fared just as well in the 2017 CHAMPION Post-Approval Study.

The Friday Hot Lines also include Dal-GenE, which has entered about 6,000 patients with recent MI to test the once-abandoned cholesterol ester transfer protein (CETP) inhibitor dalcetrapib (DalCor) for any secondary-prevention benefits when used selectively. The trial’s hook: All its patients are confirmed to have the AA genotype of the rs1967309 variant in the ADCY9 gene, which has been associated with a pronounced clinical response to CETP inhibition.

Saturday, Aug. 28

The direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists in patients with nonvalvular atrial fibrillation (AFib). But whether DOACs are similarly preferable in the growing world population of people who have undergone transcatheter aortic valve replacement (TAVR or TAVI), an issue explored with variable results in the ATLANTIS and GALILEO trials, is far from settled.

The ENVISAGE-TAVI AF trial explored the question for the factor X inhibitor edoxaban (Savaysa, Lixiana, Daiichi-Sankyo) in 1,400 patients with AFib and a transfemoral TAVR in the previous 5 days, who were randomly assigned to the DOAC or standard management along with discretionary antiplatelet therapy. They’ve been followed for up to 3 years for a composite endpoint of clinical events – including death, MI, and stroke – and for major bleeding.

The day will also feature MASTER DAPT, a comparison of two dual-antiplatelet therapy (DAPT) regimens in an estimated 4,300 patients considered to be high-risk for bleeding who had received the sirolimus-eluting Ultimaster (Terumo) coronary stent, which has a bioresorbable polymer coating.

Investigators have randomly assigned patients to receive either very-short-duration DAPT, for about a month after stenting, followed by a P2Y12 inhibitor alone for up to a year after the procedure; or a more conventional regimen of a P2Y12 inhibitor for 6-12 months with aspirin maintained for a total of 12 months.

Later that day, investigators from the FIGARO-DKD trial will present their results based on 7,437 patients with type 2 diabetes and chronic kidney disease (CKD), a much fuller version than the top-line findings announced by sponsor Bayer 3 months ago.

Those top-line results suggested that patients assigned to receive the nonsteroidal nonselective mineralocorticoid receptor antagonist (MRA) finerenone (Kerendia) on top of standard care benefited with a drop in risk for the primary endpoint of CV death or nonfatal CV events.

Finerenone was recently approved in the United States for treating patients with both type 2 diabetes and CKD based on the published FIDELIO-DKD trial, which had seen less CKD progression and fewer CV events in such patients who took the novel MRA.

Although similar in design to FIGARO-DKD, FIDELIO-DKD had entered fewer patients with early-stage diabetic kidney disease (DKD). That led researchers to pool the two trials’ populations to create a cohort that spans the spectrum of DKD severity. An analysis of the pooled cohort, dubbed FIDELITY, is on the schedule after FIGARO-DKD.

After FIDELITY is the prospective APAF-CRT trial that is following a projected 1,830 patients with permanent, symptomatic AFib and a recent hospitalization for AFib or HF and who were not good candidates for standard ablation. They were assigned to receive either atrioventricular junctional ablation followed by CRT, with or without a defibrillation, on top of optimal meds – a so-called “ablate-and-pace” strategy – or an implantable cardioverter defibrillator with rate-control drug therapy.

The new analysis represents the trial’s second phase in which mortality was followed for 4 years as the primary endpoint, in contrast to the previously reported initial phase that followed the first 102 patients for 2 years for the composite primary endpoint of death, worsening HF, and HF hospitalization. The first phase had halted enrollment before reaching its planned target of 280 patients after an interim analysis showed a significant benefit for ablate and pace. 

Next up: DECAAF 2, a randomized assessment of whether catheter ablation for AFib guided by delayed gadolinium enhancement on MRI, a proxy for scar tissue, can be more effective than standard AFib ablation by pulmonary vein isolation alone. An estimated 900 patients with persistent AFib who had never before undergone ablation for the arrhythmia were randomly assigned to one strategy or the other and followed for AFib recurrence over 18 months.
 

Sunday, Aug. 29

The TOMAHAWK trial aimed to clarify the optimal timing of invasive coronary angiography for resuscitated patients with non–ST-segment elevation out-of-hospital cardiac arrest, a broad population in a setting for which there is little randomized-trial guidance. Investigators randomly assigned 558 such patients to undergo immediate invasive angiography or to direct intensive care unit admission for initial standard care with discretionary delayed angiography. Patients were followed for all-cause mortality, with other clinical events and neurologic outcomes as secondary endpoints.

Next on the schedule, the RIPCORD-2 trial randomly assigned 1,100 patients with stable known or suspected coronary artery disease (CAD) to undergo conventional angiography alone or with added direct pressure-wire measurement of fractional flow reserve to guide management decisions. Primary outcomes include health care costs and patient-reported quality of life at 1 year.

Slated for later that day, the Asymptomatic Carotid Surgery Trial-2 (ACST-2) has entered an estimated 3600 patients with a substantial carotid artery narrowing not associated with symptoms but for which either carotid endarterectomy (CEA) or carotid artery stenting (CAS) was considered anatomically feasible. There also must have been “substantial uncertainty” regarding the optimal procedure choice.

The trial, conducted in 40 countries primarily in Europe and North America and launched in 2008, randomly assigned the patients to undergo either CEA or CAS, in both cases with appropriate medical therapy, and followed them for periprocedural events and up to 10 years for strokes and stroke-related events.

The LOOP study, which is to directly follow ACST-2, has explored whether screening for AFib using the Medtronic Reveal LINQ monitor in older patients with non-AFib stroke risk factors – with oral anticoagulation prescribed for those who test positive – can lower their risk for stroke or systemic embolism. It randomly assigned 6,000 such patients to care guided by the loop recorder or to standard care.

On a somewhat larger scale, the Salt Substitute and Stroke Study (SSaSS) randomly assigned a total of 20,996 people in about 600 villages across northern China and Tibet to sodium-restriction intervention and control groups by village. All participants had a history of stroke or were aged at least 60 years with uncontrolled hypertension.

As described by the trial’s online portal, participants in villages assigned to the intervention group were given a supply of a low-sodium, potassium-supplementing salt substitute to replace their own salt supplies, along with education on the health benefits of sodium restriction. Participants in control villages continued their normal diets and, at the trial’s beginning, received “advice to reduce their salt intake.” All were required to own a telephone.

Clinical events, including strokes and hospitalizations throughout a 5-year follow-up, were tracked by phone calls made to all participants every 6 months and were documented at follow-up home visits.

Sunday is also to feature a Late-Breaking Trials session with a focus on COVID-19, which leads off with COLCOVID, a test of colchicine in patients hospitalized for suspected SARS-CoV-2 infection and in acute respiratory distress.

The 1,279 participants in Argentina were randomly assigned to receive or not receive the potent anti-inflammatory agent on top of antivirals and other standard management and followed for death or new need for mechanical ventilation. A successful outcome would contrast with the RECOVERY trial, which terminated a colchicine group of patients hospitalized with COVID-19 because of a lack of efficacy earlier this year.

COLCOVID is to be followed by the MICHELLE trial of rivaroxaban (Xarelto, Bayer/Janssen) prophylaxis, compared with no preventive oral anticoagulant, in 320 patients who, when hospitalized with COVID-19, had been on parenteral anticoagulants because of an elevated risk for venous thromboembolism. The trial, conducted in Brazil, called for postdischarge rivaroxaban at a once-daily dosage of 10 mg for about 1 month.

The session also includes a presentation called “Insights into the Effects of the COVID-19 Pandemic: Comprehensive Analysis from the GUIDE-HF Trial,” the primary outcomes of which will be reported on the first day of the Congress.

Following is a presentation on the PREPARE-IT study of icosapent ethyl (Vascepa, Amarin), given at high dosages intended to be anti-inflammatory, compared with placebo, in an estimated 4,000 adults. The trial has two groups: A prevention group of adults living and circulating in the community; and a treatment group of patients aged at least 40 years with confirmed symptomatic SARS-CoV-2 infection for whom the need for hospitalization isn’t clear.
 

Monday, Aug. 30

The final day of the Congress features a trial called Influenza Vaccination after Myocardial Infarction (IAMI), which has tested the secondary preventive effect of influenza vaccination by randomly assigning 2,571 patients to receive a standard vaccine or a saline placebo injection on one occasion.

Entry to the international trial called for a diagnosis of MI with or without ST-segment elevation, or stable CAD and age at least 75 years with other risk factors. The patients were followed for death, MI, stent thrombosis, and a slew of secondary endpoints over 12 months.

Monday offerings continue later in a time block leading off with the STEP trial, which has randomly assigned an estimated 8,000 patients at 40 centers in China who are 60 to 80 years of age with a systolic blood pressure of 140 to <190 mm Hg to be on standard guideline-based therapy or an intensive drug-management strategy.

The systolic BP goals are 130 to <150 mm Hg for standard care and 110 to <130 mm Hg for the intensive regimen. The composite primary endpoint includes death and clinical events related to acute coronary syndromes, HF, revascularization, and stroke.

Following on heels of STEP, the Amulet IDE trial – the first major randomized comparison of two transcatheter LAA closure devices – entered 1,878 patients with nonvalvular AFib who were considered high-risk for bleeding and stroke or systemic embolism.

They were randomly assigned in the noninferiority trial to receive either the AMPLATZER Amulet (Abbott Medical Devices) or the WATCHMAN (Boston Scientific) closure devices and were followed for safety and efficacy for up to 5 years.

Both LAA closure devices, intended to make patients with AFib less reliant on oral anticoagulation, are now available on both sides of the Atlantic – as well as many other countries – after the Amulet’s United States market approval on Aug. 16, based largely on the Amulet IDE trial.

Rounding out the final Hot Line set is one of the latest efforts to show the efficacy and safety of a very short DAPT period after coronary stenting in patients with acute coronary syndromes, the STOPDAPT-2 ACS trial.

The study assigned 3,008 patients in Japan to receive aspirin and clopidogrel for either 1 month or 1 year after implantation with an everolimus-eluting cobalt-chromium stent and followed them for up to 5 years for a composite of MI, CV death, stent thrombosis, stroke, and bleeding.

The trial follows the published STOPDAPT-2 trial that showed superiority for the 1-month DAPT regimen in a predominantly stable-CAD population treated with the same kind of stent.
 

Program structure and format

A total of 15 online channels are to be available in the morning, European time, their schedules running in parallel. Presentations often are prerecorded, but also include live sessions at 8:00 a.m. Central time and 12 p.m. CET (2:00 a.m. and 6:00 a.m. Eastern time) to liven up the channel offerings, Dr. Windecker observed, and to make them more immediate and potentially interactive.

Many of the parallel channels are devoted throughout the Congress to particular silos of cardiology; for example, arrhythmias and device therapy is on channel 3; CAD and acute care is on 5; HF is on 6; and preventive cardiology is on 9.

Other channels swing across different topics from day to day, such as channel 1, which covers COVID-19 topics on the first and third day of the meeting, “advances in science” on day 2, and “digital health, public health, health economics” on day 4.

The focus each day, starting at 2:00 p.m. CET (8:00 a.m. ET) and continuing into the evening in Europe, shifts over to the Prime Time live program, which features the Hot Line and guideline presentations and many of the live abstract presentations.

Dr. Kosiborod, not a researcher with the EMPEROR trials, is chair of the Dapagliflozin in Preserved Ejection Fraction Heart Failure ( PRESERVED-HF ) trial, which is scheduled for presentation at the September 2021 Heart Failure Society of American meeting.

A version of this article first appeared on Medscape.com.

There will be so much more to the annual congress of the European Society of Cardiology, which begins Aug. 27 with an all-virtual format, than detailed primary results of EMPEROR-Preserved, a trial that could mark a turning point for heart failure (HF) medical therapy.

Also among the featured Hot Line and Late-Breaking Science sessions are – along with many other studies – explorations of arrhythmia management (ablation or guided by loop recorder); secondary prevention, including by vaccination; oral anticoagulation, notably after transcatheter valve procedures; and colchicine or thrombosis prophylaxis in hospitalized patients with COVID-19.

There will even be a head-to-head comparison of two long-familiar left atrial appendage (LAA) occluders, and a population-based, randomized trial of sodium restriction through wide-scale use of a potassium-based salt substitute.

The congress will also introduce four guideline documents at sessions throughout the Congress, one on each day. They cover new and modified recommendations for heart failure; pacing, including cardiac resynchronization therapy (CRT); cardiovascular (CV) disease prevention; and, with cosponsorship from the European Association for Cardio-Thoracic Surgery, valvular heart disease.
 

The virtues of virtual

That next year’s Congress is slated for Aug. 27-30 in Barcelona should be welcome news for anyone whose “what if” curiosity about all-virtual conferences has already been satisfied. But with experience comes wisdom, as the medical societies have learned that online scientific meetings have some winning qualities that may be worth keeping, as least for a while.

“I think there is no doubt that the digital format will continue, for several reasons. One is that this pandemic is not over,” ESC Congress program committee chair Stephan Windecker, MD, Bern (Switzerland) University Hospital, , told this news organization. “As long as it is not over, the digital format is here to stay.”

But it also appears that people who haven’t been able to attend the congress in person are keen to log in and engage online, Dr. Windecker said. The 2020 all-virtual conference drew a much younger pool of registrants, on average, than did the live conferences before the pandemic.

“I think that’s an indication of people that may be in training, in early stages of their career, or they don’t have the support from departments or from their practice, or other financial means.” But they are able to participate via computer, tablet, or smartphone, he said.

“Another advantage is that the recorded content can be replayed at the convenience of whoever wants to consume it at a later point in time,” he added. “Those are just some examples why the digital format is likely to stay,” on its own or in a new age of hybrid meetings.  
 

New and updated guidelines

Leading off the guideline series is the document on diagnosis and treatment of acute and chronic HF, which leveraged the past few busy years of HF clinical trials to arrive at a number of new recommendations and strengthened level-of-evidence ratings. It covers both drug and device therapy of HF with reduced ejection fraction (HFrEF) and acute decompensated HF, and tweaks and further enshrines the concept of HF with mildly reduced ejection fraction (HFmrEF).

Several updated recommendations for both long-used and novel medications, notably the sodium-glucose cotransporter 2 inhibitors, will be included because of the recently appreciated evidence-based impact in HFrEF, Dr. Windecker noted.

“I think it will be particularly interesting to look for the SGLT2 inhibitors as not a completely new class of drugs, but certainly one where there has been a lot of new evidence, to look at how those drugs will be integrated in the overall care pathway.”

A top-line preview of the new HF guideline limited to drug therapy, presented at July’s Heart Failure Association of the European Society of Cardiology (ESC-HFA), provided a simple answer to a common question in the new, bountiful age of HFrEF medications: Which meds, initiated in what order?

As it happens, the new recommendation for first-line HFrEF drug therapy is not a silver bullet, but a shotgun – prompt initiation of at least four meds, one from each of four drug classes: renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRA), and SGLT2 inhibitors. Each class, as described in the document, is to be started as soon as safely feasible, in a sequence deemed appropriate for each individual patient.
 

Spotlight on EMPEROR-Preserved

The world already knows that the trial, which tested the SGLT2 inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) on top of standard therapy, “met” its primary endpoint in almost 6,000 patients with HF with preserved ejection fraction (HFpEF), who included some with HFmrEF by more contemporary definitions.

That means patients in EMPEROR-Preserved assigned to take empagliflozin showed significantly fewer events that made up the study’s primary endpoint, a composite of CV death or HF hospitalization. It appears to be the first clearly significant overall medical therapy benefit for a clinical primary endpoint in a major randomized HFpEF drug trial.

And that, pending fuller presentation of trial results at the Congress on Aug. 27, could be a huge deal for the half of HF patients with left ventricular ejection fractions (LVEF) higher than the HFrEF range.

Those early top-line results weren’t a decisive bombshell for a field now filled with hope for a practice-changing empagliflozin outcome in EMPEROR-Preserved, which isn’t a certainty. They were more like the “boom” of a mortar launching a rocket of fireworks that may explode into a chrysanthemum or green comet or, sometimes, turn out to be no more than a dud. The promise of the early cursory results critically depends on further details.

“Provided there is a compelling benefit, this is what everyone has been waiting for in this condition for decades,” Mikhail N. Kosiborod, MD, director of cardiometabolic research at Saint Luke’s Mid-America Heart Institute, Kansas City, Mo., said.

“Already knowing that the trial met the primary endpoint is obviously very intriguing and encouraging,” he added. “But there are things we don’t know, such as: What is the magnitude of benefit? And whether that benefit, whatever the magnitude, is driven by reductions in both heart failure hospitalizations and cardiovascular death, or only one of the two.”

For example: “If we see an impressive benefit for reduction of hospitalizations, but not a significant reduction in death, that would still be a huge advance. That’s because, to date, we don’t have any drug for HFpEF that has convincingly demonstrated a compelling reduction in heart failure hospitalization or improvement in symptoms, function, or quality of life,” observed Dr. Kosiborod, who wasn’t part of EMPEROR-Preserved.

There have been “suggestions” from HFrEF trials that empagliflozin and dapagliflozin (Farxiga, AstraZeneca) “have very comparable effects on at least the endpoint of cardiovascular death or hospitalization for heart failure,” he said. “So, my expectation would be that whatever is observed in EMPEROR-Preserved is likely a class effect, as well.”

Following EMPEROR-Preserved on the agenda is EMPEROR-Pooled, a patient-level combined analysis of the EMPEROR series of trials that spans the range of HF, regardless of ejection fraction or diabetes status, primarily exploring the effects of empagliflozin on renal function.
 

Other offerings, Friday, Aug. 27

Scheduled immediately after EMPEROR-Preserved is a presentation on the SMART-MI trial, which should clarify whether management guided by continuous ambulatory monitoring is effective in patients considered at especially high arrhythmic risk. Entry called for recent myocardial infarction and an LVEF of 36%-50% with evidence of cardiac autonomic dysfunction.

The trial randomly assigned 400 such patients to be or not be implanted with a Reveal LINQ (Medtronic) loop recorder and followed them for up to 18 months, primarily for detection of potentially serious arrhythmic events. Endpoints that involved mortality, hospitalization or other clinical events were secondary.

In a time slot preceding both SMART-MI and EMPEROR-Preserved, the GUIDE-HF trial is following a projected 3,600 patients with HF implanted with a CardioMEMS HF System (Abbott) pulmonary artery (PA) pressure sensor to explore the its value for guiding management.

The trial’s three cohorts, followed for at least 12 months, include randomized sensor-monitored and control groups of patients with New York Heart Association class 2-4 symptoms, as well as a third observational set of patients in NYHA class 3. That’s the indication for which the CardioMEMS monitor gained approval in the United States in 2014 based on the 2011 CHAMPION trial, and which fared just as well in the 2017 CHAMPION Post-Approval Study.

The Friday Hot Lines also include Dal-GenE, which has entered about 6,000 patients with recent MI to test the once-abandoned cholesterol ester transfer protein (CETP) inhibitor dalcetrapib (DalCor) for any secondary-prevention benefits when used selectively. The trial’s hook: All its patients are confirmed to have the AA genotype of the rs1967309 variant in the ADCY9 gene, which has been associated with a pronounced clinical response to CETP inhibition.

Saturday, Aug. 28

The direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists in patients with nonvalvular atrial fibrillation (AFib). But whether DOACs are similarly preferable in the growing world population of people who have undergone transcatheter aortic valve replacement (TAVR or TAVI), an issue explored with variable results in the ATLANTIS and GALILEO trials, is far from settled.

The ENVISAGE-TAVI AF trial explored the question for the factor X inhibitor edoxaban (Savaysa, Lixiana, Daiichi-Sankyo) in 1,400 patients with AFib and a transfemoral TAVR in the previous 5 days, who were randomly assigned to the DOAC or standard management along with discretionary antiplatelet therapy. They’ve been followed for up to 3 years for a composite endpoint of clinical events – including death, MI, and stroke – and for major bleeding.

The day will also feature MASTER DAPT, a comparison of two dual-antiplatelet therapy (DAPT) regimens in an estimated 4,300 patients considered to be high-risk for bleeding who had received the sirolimus-eluting Ultimaster (Terumo) coronary stent, which has a bioresorbable polymer coating.

Investigators have randomly assigned patients to receive either very-short-duration DAPT, for about a month after stenting, followed by a P2Y12 inhibitor alone for up to a year after the procedure; or a more conventional regimen of a P2Y12 inhibitor for 6-12 months with aspirin maintained for a total of 12 months.

Later that day, investigators from the FIGARO-DKD trial will present their results based on 7,437 patients with type 2 diabetes and chronic kidney disease (CKD), a much fuller version than the top-line findings announced by sponsor Bayer 3 months ago.

Those top-line results suggested that patients assigned to receive the nonsteroidal nonselective mineralocorticoid receptor antagonist (MRA) finerenone (Kerendia) on top of standard care benefited with a drop in risk for the primary endpoint of CV death or nonfatal CV events.

Finerenone was recently approved in the United States for treating patients with both type 2 diabetes and CKD based on the published FIDELIO-DKD trial, which had seen less CKD progression and fewer CV events in such patients who took the novel MRA.

Although similar in design to FIGARO-DKD, FIDELIO-DKD had entered fewer patients with early-stage diabetic kidney disease (DKD). That led researchers to pool the two trials’ populations to create a cohort that spans the spectrum of DKD severity. An analysis of the pooled cohort, dubbed FIDELITY, is on the schedule after FIGARO-DKD.

After FIDELITY is the prospective APAF-CRT trial that is following a projected 1,830 patients with permanent, symptomatic AFib and a recent hospitalization for AFib or HF and who were not good candidates for standard ablation. They were assigned to receive either atrioventricular junctional ablation followed by CRT, with or without a defibrillation, on top of optimal meds – a so-called “ablate-and-pace” strategy – or an implantable cardioverter defibrillator with rate-control drug therapy.

The new analysis represents the trial’s second phase in which mortality was followed for 4 years as the primary endpoint, in contrast to the previously reported initial phase that followed the first 102 patients for 2 years for the composite primary endpoint of death, worsening HF, and HF hospitalization. The first phase had halted enrollment before reaching its planned target of 280 patients after an interim analysis showed a significant benefit for ablate and pace. 

Next up: DECAAF 2, a randomized assessment of whether catheter ablation for AFib guided by delayed gadolinium enhancement on MRI, a proxy for scar tissue, can be more effective than standard AFib ablation by pulmonary vein isolation alone. An estimated 900 patients with persistent AFib who had never before undergone ablation for the arrhythmia were randomly assigned to one strategy or the other and followed for AFib recurrence over 18 months.
 

Sunday, Aug. 29

The TOMAHAWK trial aimed to clarify the optimal timing of invasive coronary angiography for resuscitated patients with non–ST-segment elevation out-of-hospital cardiac arrest, a broad population in a setting for which there is little randomized-trial guidance. Investigators randomly assigned 558 such patients to undergo immediate invasive angiography or to direct intensive care unit admission for initial standard care with discretionary delayed angiography. Patients were followed for all-cause mortality, with other clinical events and neurologic outcomes as secondary endpoints.

Next on the schedule, the RIPCORD-2 trial randomly assigned 1,100 patients with stable known or suspected coronary artery disease (CAD) to undergo conventional angiography alone or with added direct pressure-wire measurement of fractional flow reserve to guide management decisions. Primary outcomes include health care costs and patient-reported quality of life at 1 year.

Slated for later that day, the Asymptomatic Carotid Surgery Trial-2 (ACST-2) has entered an estimated 3600 patients with a substantial carotid artery narrowing not associated with symptoms but for which either carotid endarterectomy (CEA) or carotid artery stenting (CAS) was considered anatomically feasible. There also must have been “substantial uncertainty” regarding the optimal procedure choice.

The trial, conducted in 40 countries primarily in Europe and North America and launched in 2008, randomly assigned the patients to undergo either CEA or CAS, in both cases with appropriate medical therapy, and followed them for periprocedural events and up to 10 years for strokes and stroke-related events.

The LOOP study, which is to directly follow ACST-2, has explored whether screening for AFib using the Medtronic Reveal LINQ monitor in older patients with non-AFib stroke risk factors – with oral anticoagulation prescribed for those who test positive – can lower their risk for stroke or systemic embolism. It randomly assigned 6,000 such patients to care guided by the loop recorder or to standard care.

On a somewhat larger scale, the Salt Substitute and Stroke Study (SSaSS) randomly assigned a total of 20,996 people in about 600 villages across northern China and Tibet to sodium-restriction intervention and control groups by village. All participants had a history of stroke or were aged at least 60 years with uncontrolled hypertension.

As described by the trial’s online portal, participants in villages assigned to the intervention group were given a supply of a low-sodium, potassium-supplementing salt substitute to replace their own salt supplies, along with education on the health benefits of sodium restriction. Participants in control villages continued their normal diets and, at the trial’s beginning, received “advice to reduce their salt intake.” All were required to own a telephone.

Clinical events, including strokes and hospitalizations throughout a 5-year follow-up, were tracked by phone calls made to all participants every 6 months and were documented at follow-up home visits.

Sunday is also to feature a Late-Breaking Trials session with a focus on COVID-19, which leads off with COLCOVID, a test of colchicine in patients hospitalized for suspected SARS-CoV-2 infection and in acute respiratory distress.

The 1,279 participants in Argentina were randomly assigned to receive or not receive the potent anti-inflammatory agent on top of antivirals and other standard management and followed for death or new need for mechanical ventilation. A successful outcome would contrast with the RECOVERY trial, which terminated a colchicine group of patients hospitalized with COVID-19 because of a lack of efficacy earlier this year.

COLCOVID is to be followed by the MICHELLE trial of rivaroxaban (Xarelto, Bayer/Janssen) prophylaxis, compared with no preventive oral anticoagulant, in 320 patients who, when hospitalized with COVID-19, had been on parenteral anticoagulants because of an elevated risk for venous thromboembolism. The trial, conducted in Brazil, called for postdischarge rivaroxaban at a once-daily dosage of 10 mg for about 1 month.

The session also includes a presentation called “Insights into the Effects of the COVID-19 Pandemic: Comprehensive Analysis from the GUIDE-HF Trial,” the primary outcomes of which will be reported on the first day of the Congress.

Following is a presentation on the PREPARE-IT study of icosapent ethyl (Vascepa, Amarin), given at high dosages intended to be anti-inflammatory, compared with placebo, in an estimated 4,000 adults. The trial has two groups: A prevention group of adults living and circulating in the community; and a treatment group of patients aged at least 40 years with confirmed symptomatic SARS-CoV-2 infection for whom the need for hospitalization isn’t clear.
 

Monday, Aug. 30

The final day of the Congress features a trial called Influenza Vaccination after Myocardial Infarction (IAMI), which has tested the secondary preventive effect of influenza vaccination by randomly assigning 2,571 patients to receive a standard vaccine or a saline placebo injection on one occasion.

Entry to the international trial called for a diagnosis of MI with or without ST-segment elevation, or stable CAD and age at least 75 years with other risk factors. The patients were followed for death, MI, stent thrombosis, and a slew of secondary endpoints over 12 months.

Monday offerings continue later in a time block leading off with the STEP trial, which has randomly assigned an estimated 8,000 patients at 40 centers in China who are 60 to 80 years of age with a systolic blood pressure of 140 to <190 mm Hg to be on standard guideline-based therapy or an intensive drug-management strategy.

The systolic BP goals are 130 to <150 mm Hg for standard care and 110 to <130 mm Hg for the intensive regimen. The composite primary endpoint includes death and clinical events related to acute coronary syndromes, HF, revascularization, and stroke.

Following on heels of STEP, the Amulet IDE trial – the first major randomized comparison of two transcatheter LAA closure devices – entered 1,878 patients with nonvalvular AFib who were considered high-risk for bleeding and stroke or systemic embolism.

They were randomly assigned in the noninferiority trial to receive either the AMPLATZER Amulet (Abbott Medical Devices) or the WATCHMAN (Boston Scientific) closure devices and were followed for safety and efficacy for up to 5 years.

Both LAA closure devices, intended to make patients with AFib less reliant on oral anticoagulation, are now available on both sides of the Atlantic – as well as many other countries – after the Amulet’s United States market approval on Aug. 16, based largely on the Amulet IDE trial.

Rounding out the final Hot Line set is one of the latest efforts to show the efficacy and safety of a very short DAPT period after coronary stenting in patients with acute coronary syndromes, the STOPDAPT-2 ACS trial.

The study assigned 3,008 patients in Japan to receive aspirin and clopidogrel for either 1 month or 1 year after implantation with an everolimus-eluting cobalt-chromium stent and followed them for up to 5 years for a composite of MI, CV death, stent thrombosis, stroke, and bleeding.

The trial follows the published STOPDAPT-2 trial that showed superiority for the 1-month DAPT regimen in a predominantly stable-CAD population treated with the same kind of stent.
 

Program structure and format

A total of 15 online channels are to be available in the morning, European time, their schedules running in parallel. Presentations often are prerecorded, but also include live sessions at 8:00 a.m. Central time and 12 p.m. CET (2:00 a.m. and 6:00 a.m. Eastern time) to liven up the channel offerings, Dr. Windecker observed, and to make them more immediate and potentially interactive.

Many of the parallel channels are devoted throughout the Congress to particular silos of cardiology; for example, arrhythmias and device therapy is on channel 3; CAD and acute care is on 5; HF is on 6; and preventive cardiology is on 9.

Other channels swing across different topics from day to day, such as channel 1, which covers COVID-19 topics on the first and third day of the meeting, “advances in science” on day 2, and “digital health, public health, health economics” on day 4.

The focus each day, starting at 2:00 p.m. CET (8:00 a.m. ET) and continuing into the evening in Europe, shifts over to the Prime Time live program, which features the Hot Line and guideline presentations and many of the live abstract presentations.

Dr. Kosiborod, not a researcher with the EMPEROR trials, is chair of the Dapagliflozin in Preserved Ejection Fraction Heart Failure ( PRESERVED-HF ) trial, which is scheduled for presentation at the September 2021 Heart Failure Society of American meeting.

A version of this article first appeared on Medscape.com.

The United States Preventive Services Task Force has updated its recommendation on the age of screening for prediabetes and type 2 diabetes in the primary care setting – lowering the age from 40 to 35 years for asymptomatic patients who are overweight or obese and encouraging greater interventions when patients do show a risk.

KatarzynaBialasiewicz/Thinkstock

“The USPSTF concludes with moderate certainty that screening for prediabetes and type 2 diabetes and offering or referring patients with prediabetes to effective preventive interventions has a moderate net benefit,” the task force concludes in its recommendation, published Aug. 24 in JAMA.

“Clinicians should offer or refer patients with prediabetes to effective preventive interventions,” they write.

Experts commenting on the issue strongly emphasize that it’s not just the screening, but the subsequent intervention that is needed to make a difference.

“If young adults newly identified with abnormal glucose metabolism do not receive the needed intensive behavioral change support, screening may provide no benefit,” write Richard W. Grant, MD, MPH, and colleagues in an editorial published with the recommendation.

“Given the role of our obesogenic and physically inactive society in the shift toward earlier onset of diabetes, efforts to increase screening and recognition of abnormal glucose metabolism must be coupled with robust public health measures to address the underlying contributors.”
 

BMI cutoff lower for at-risk ethnic populations

The recommendation, which updates the task force’s 2015 guideline, carries a “B” classification, meaning the USPSTF has high certainty that the net benefit is moderate. It now specifies screening from age 35to 70 for persons classified as overweight (body mass index at least 25) or obese (BMI at least 30) and recommends referral to preventive interventions when patients are found to have prediabetes.

In addition to recommendations of lifestyle changes, such as diet and physical activity, the task force also endorses the diabetes drug metformin as a beneficial intervention in the prevention or delay of diabetes, while noting fewer overall health benefits from metformin than from the lifestyle changes.

A lower BMI cutoff of at least 23 is recommended for diabetes screening of Asian Americans, and, importantly, screening for prediabetes and diabetes should be considered at an even earlier age if the patient is from a population with a disproportionately high prevalence of diabetes, including American Indian/Alaska Native, Black, Hawaiian/Pacific Islander, Hispanic/Latino, the task force recommends.

Screening tests should include fasting plasma glucose, hemoglobin A1c, or an oral glucose tolerance test. Although screening every 3 years “may be a reasonable approach for adults with normal blood glucose levels,” the task force adds that “the optimal screening interval for adults with an initial normal glucose test result is uncertain.”
 

Data review: Few with prediabetes know they have it

The need for the update was prompted by troubling data showing increasing diabetes rates despite early signs that can and should be identified and acted upon in the primary care setting to prevent disease progression.

Data from the Centers for Disease Control and Prevention, for instance, show that while 13% of all U.S. adults 18 years or older have diabetes and 35% meet criteria for prediabetes, as many as 21% of those with diabetes were not aware of or did not report having the disease. Furthermore, only a small fraction – 15% of those with prediabetes – said they had been told by a health professional that they had this condition, the task force notes.

The task force’s final recommendation was based on a systematic review of evidence regarding the screening of asymptomatic, nonpregnant adults and the harms and benefits of interventions, such as physical activity, behavioral counseling, or pharmacotherapy.

Among key evidence supporting the lower age was a 2014 study showing that the number of people necessary to obtain one positive test for diabetes with screening sharply drops from 80 among those aged 30-34 years to just 31 among those aged 36-39.

Opportunistic universal screening of eligible people aged 35 and older would yield a ratio of 1 out of just 15 to spot a positive test, the authors of that study reported.

In addition, a large cohort study in more than 77,000 people with prediabetes strongly links the risk of developing diabetes with increases in A1c level and with increasing BMI.
 

ADA recommendations differ

The new recommendations differ from American Diabetes Association guidelines, which call for diabetes screening at all ages for people who are overweight or obese and who have one or more risk factors, such as physical inactivity or a first-degree relative with diabetes. If results are normal, repeat screening at least every 3 years is recommended.

The ADA further recommends universal screening for all adults 45 years and older, regardless of their risk factors.

For the screening of adults over 45, the ADA recommends using a fasting plasma glucose level, 2-hour plasma glucose level during a 75-g oral glucose tolerance test, or A1c level, regardless of risk factors.

The American Association of Clinical Endocrinology also recommends universal screening for prediabetes and diabetes for all adults 45 years or older, regardless of risk factors, and also advises screening those who have risk factors for diabetes regardless of age.
 

Screening of little benefit without behavior change support

In an interview, Dr. Grant added that broad efforts are essential as those at the practice level have clearly not succeeded.

“The medical model of individual counseling and referral has not really been effective, and so we really need to think in terms of large-scale public health action,” said Dr. Grant, of the division of research, Kaiser Permanente Northern California, Oakland.

His editorial details the sweeping, multifactorial efforts that are needed.

“To turn this recommendation into action – that is, to translate screening activities into improved clinical outcomes – change is needed at the patient-clinician level (recognizing and encouraging eligible individuals to be screened), health care system level (reducing screening barriers and ensuring access to robust lifestyle programs), and societal level (applying effective public health interventions to reduce obesity and increase exercise),” they write.

A top priority has to be a focus on individuals of diverse backgrounds and issues such as access to healthy programs in minority communities, Dr. Grant noted.

“Newly diagnosed adults are more likely to be African-American and Latinx,” he said.

“We really need to invest in healthier communities for low-income, non-White communities to reverse the persistent health care disparities in these communities.”

While the challenges may appear daunting, history shows they are not necessarily insurmountable – as evidenced in the campaign to discourage tobacco smoking.

“National smoking cessation efforts are one example of a mostly successful public health campaign that has made a difference in health behaviors,” Grant noted.

The recommendation is also posted on the USPSTF web site .

Dr. Grant reports receiving grants from the National Institutes of Health and the Patient-Centered Outcomes Research Institute.

The United States Preventive Services Task Force has updated its recommendation on the age of screening for prediabetes and type 2 diabetes in the primary care setting – lowering the age from 40 to 35 years for asymptomatic patients who are overweight or obese and encouraging greater interventions when patients do show a risk.

KatarzynaBialasiewicz/Thinkstock

“The USPSTF concludes with moderate certainty that screening for prediabetes and type 2 diabetes and offering or referring patients with prediabetes to effective preventive interventions has a moderate net benefit,” the task force concludes in its recommendation, published Aug. 24 in JAMA.

“Clinicians should offer or refer patients with prediabetes to effective preventive interventions,” they write.

Experts commenting on the issue strongly emphasize that it’s not just the screening, but the subsequent intervention that is needed to make a difference.

“If young adults newly identified with abnormal glucose metabolism do not receive the needed intensive behavioral change support, screening may provide no benefit,” write Richard W. Grant, MD, MPH, and colleagues in an editorial published with the recommendation.

“Given the role of our obesogenic and physically inactive society in the shift toward earlier onset of diabetes, efforts to increase screening and recognition of abnormal glucose metabolism must be coupled with robust public health measures to address the underlying contributors.”
 

BMI cutoff lower for at-risk ethnic populations

The recommendation, which updates the task force’s 2015 guideline, carries a “B” classification, meaning the USPSTF has high certainty that the net benefit is moderate. It now specifies screening from age 35to 70 for persons classified as overweight (body mass index at least 25) or obese (BMI at least 30) and recommends referral to preventive interventions when patients are found to have prediabetes.

In addition to recommendations of lifestyle changes, such as diet and physical activity, the task force also endorses the diabetes drug metformin as a beneficial intervention in the prevention or delay of diabetes, while noting fewer overall health benefits from metformin than from the lifestyle changes.

A lower BMI cutoff of at least 23 is recommended for diabetes screening of Asian Americans, and, importantly, screening for prediabetes and diabetes should be considered at an even earlier age if the patient is from a population with a disproportionately high prevalence of diabetes, including American Indian/Alaska Native, Black, Hawaiian/Pacific Islander, Hispanic/Latino, the task force recommends.

Screening tests should include fasting plasma glucose, hemoglobin A1c, or an oral glucose tolerance test. Although screening every 3 years “may be a reasonable approach for adults with normal blood glucose levels,” the task force adds that “the optimal screening interval for adults with an initial normal glucose test result is uncertain.”
 

Data review: Few with prediabetes know they have it

The need for the update was prompted by troubling data showing increasing diabetes rates despite early signs that can and should be identified and acted upon in the primary care setting to prevent disease progression.

Data from the Centers for Disease Control and Prevention, for instance, show that while 13% of all U.S. adults 18 years or older have diabetes and 35% meet criteria for prediabetes, as many as 21% of those with diabetes were not aware of or did not report having the disease. Furthermore, only a small fraction – 15% of those with prediabetes – said they had been told by a health professional that they had this condition, the task force notes.

The task force’s final recommendation was based on a systematic review of evidence regarding the screening of asymptomatic, nonpregnant adults and the harms and benefits of interventions, such as physical activity, behavioral counseling, or pharmacotherapy.

Among key evidence supporting the lower age was a 2014 study showing that the number of people necessary to obtain one positive test for diabetes with screening sharply drops from 80 among those aged 30-34 years to just 31 among those aged 36-39.

Opportunistic universal screening of eligible people aged 35 and older would yield a ratio of 1 out of just 15 to spot a positive test, the authors of that study reported.

In addition, a large cohort study in more than 77,000 people with prediabetes strongly links the risk of developing diabetes with increases in A1c level and with increasing BMI.
 

ADA recommendations differ

The new recommendations differ from American Diabetes Association guidelines, which call for diabetes screening at all ages for people who are overweight or obese and who have one or more risk factors, such as physical inactivity or a first-degree relative with diabetes. If results are normal, repeat screening at least every 3 years is recommended.

The ADA further recommends universal screening for all adults 45 years and older, regardless of their risk factors.

For the screening of adults over 45, the ADA recommends using a fasting plasma glucose level, 2-hour plasma glucose level during a 75-g oral glucose tolerance test, or A1c level, regardless of risk factors.

The American Association of Clinical Endocrinology also recommends universal screening for prediabetes and diabetes for all adults 45 years or older, regardless of risk factors, and also advises screening those who have risk factors for diabetes regardless of age.
 

Screening of little benefit without behavior change support

In an interview, Dr. Grant added that broad efforts are essential as those at the practice level have clearly not succeeded.

“The medical model of individual counseling and referral has not really been effective, and so we really need to think in terms of large-scale public health action,” said Dr. Grant, of the division of research, Kaiser Permanente Northern California, Oakland.

His editorial details the sweeping, multifactorial efforts that are needed.

“To turn this recommendation into action – that is, to translate screening activities into improved clinical outcomes – change is needed at the patient-clinician level (recognizing and encouraging eligible individuals to be screened), health care system level (reducing screening barriers and ensuring access to robust lifestyle programs), and societal level (applying effective public health interventions to reduce obesity and increase exercise),” they write.

A top priority has to be a focus on individuals of diverse backgrounds and issues such as access to healthy programs in minority communities, Dr. Grant noted.

“Newly diagnosed adults are more likely to be African-American and Latinx,” he said.

“We really need to invest in healthier communities for low-income, non-White communities to reverse the persistent health care disparities in these communities.”

While the challenges may appear daunting, history shows they are not necessarily insurmountable – as evidenced in the campaign to discourage tobacco smoking.

“National smoking cessation efforts are one example of a mostly successful public health campaign that has made a difference in health behaviors,” Grant noted.

The recommendation is also posted on the USPSTF web site .

Dr. Grant reports receiving grants from the National Institutes of Health and the Patient-Centered Outcomes Research Institute.

The United States Preventive Services Task Force has updated its recommendation on the age of screening for prediabetes and type 2 diabetes in the primary care setting – lowering the age from 40 to 35 years for asymptomatic patients who are overweight or obese and encouraging greater interventions when patients do show a risk.

KatarzynaBialasiewicz/Thinkstock

“The USPSTF concludes with moderate certainty that screening for prediabetes and type 2 diabetes and offering or referring patients with prediabetes to effective preventive interventions has a moderate net benefit,” the task force concludes in its recommendation, published Aug. 24 in JAMA.

“Clinicians should offer or refer patients with prediabetes to effective preventive interventions,” they write.

Experts commenting on the issue strongly emphasize that it’s not just the screening, but the subsequent intervention that is needed to make a difference.

“If young adults newly identified with abnormal glucose metabolism do not receive the needed intensive behavioral change support, screening may provide no benefit,” write Richard W. Grant, MD, MPH, and colleagues in an editorial published with the recommendation.

“Given the role of our obesogenic and physically inactive society in the shift toward earlier onset of diabetes, efforts to increase screening and recognition of abnormal glucose metabolism must be coupled with robust public health measures to address the underlying contributors.”
 

BMI cutoff lower for at-risk ethnic populations

The recommendation, which updates the task force’s 2015 guideline, carries a “B” classification, meaning the USPSTF has high certainty that the net benefit is moderate. It now specifies screening from age 35to 70 for persons classified as overweight (body mass index at least 25) or obese (BMI at least 30) and recommends referral to preventive interventions when patients are found to have prediabetes.

In addition to recommendations of lifestyle changes, such as diet and physical activity, the task force also endorses the diabetes drug metformin as a beneficial intervention in the prevention or delay of diabetes, while noting fewer overall health benefits from metformin than from the lifestyle changes.

A lower BMI cutoff of at least 23 is recommended for diabetes screening of Asian Americans, and, importantly, screening for prediabetes and diabetes should be considered at an even earlier age if the patient is from a population with a disproportionately high prevalence of diabetes, including American Indian/Alaska Native, Black, Hawaiian/Pacific Islander, Hispanic/Latino, the task force recommends.

Screening tests should include fasting plasma glucose, hemoglobin A1c, or an oral glucose tolerance test. Although screening every 3 years “may be a reasonable approach for adults with normal blood glucose levels,” the task force adds that “the optimal screening interval for adults with an initial normal glucose test result is uncertain.”
 

Data review: Few with prediabetes know they have it

The need for the update was prompted by troubling data showing increasing diabetes rates despite early signs that can and should be identified and acted upon in the primary care setting to prevent disease progression.

Data from the Centers for Disease Control and Prevention, for instance, show that while 13% of all U.S. adults 18 years or older have diabetes and 35% meet criteria for prediabetes, as many as 21% of those with diabetes were not aware of or did not report having the disease. Furthermore, only a small fraction – 15% of those with prediabetes – said they had been told by a health professional that they had this condition, the task force notes.

The task force’s final recommendation was based on a systematic review of evidence regarding the screening of asymptomatic, nonpregnant adults and the harms and benefits of interventions, such as physical activity, behavioral counseling, or pharmacotherapy.

Among key evidence supporting the lower age was a 2014 study showing that the number of people necessary to obtain one positive test for diabetes with screening sharply drops from 80 among those aged 30-34 years to just 31 among those aged 36-39.

Opportunistic universal screening of eligible people aged 35 and older would yield a ratio of 1 out of just 15 to spot a positive test, the authors of that study reported.

In addition, a large cohort study in more than 77,000 people with prediabetes strongly links the risk of developing diabetes with increases in A1c level and with increasing BMI.
 

ADA recommendations differ

The new recommendations differ from American Diabetes Association guidelines, which call for diabetes screening at all ages for people who are overweight or obese and who have one or more risk factors, such as physical inactivity or a first-degree relative with diabetes. If results are normal, repeat screening at least every 3 years is recommended.

The ADA further recommends universal screening for all adults 45 years and older, regardless of their risk factors.

For the screening of adults over 45, the ADA recommends using a fasting plasma glucose level, 2-hour plasma glucose level during a 75-g oral glucose tolerance test, or A1c level, regardless of risk factors.

The American Association of Clinical Endocrinology also recommends universal screening for prediabetes and diabetes for all adults 45 years or older, regardless of risk factors, and also advises screening those who have risk factors for diabetes regardless of age.
 

Screening of little benefit without behavior change support

In an interview, Dr. Grant added that broad efforts are essential as those at the practice level have clearly not succeeded.

“The medical model of individual counseling and referral has not really been effective, and so we really need to think in terms of large-scale public health action,” said Dr. Grant, of the division of research, Kaiser Permanente Northern California, Oakland.

His editorial details the sweeping, multifactorial efforts that are needed.

“To turn this recommendation into action – that is, to translate screening activities into improved clinical outcomes – change is needed at the patient-clinician level (recognizing and encouraging eligible individuals to be screened), health care system level (reducing screening barriers and ensuring access to robust lifestyle programs), and societal level (applying effective public health interventions to reduce obesity and increase exercise),” they write.

A top priority has to be a focus on individuals of diverse backgrounds and issues such as access to healthy programs in minority communities, Dr. Grant noted.

“Newly diagnosed adults are more likely to be African-American and Latinx,” he said.

“We really need to invest in healthier communities for low-income, non-White communities to reverse the persistent health care disparities in these communities.”

While the challenges may appear daunting, history shows they are not necessarily insurmountable – as evidenced in the campaign to discourage tobacco smoking.

“National smoking cessation efforts are one example of a mostly successful public health campaign that has made a difference in health behaviors,” Grant noted.

The recommendation is also posted on the USPSTF web site .

Dr. Grant reports receiving grants from the National Institutes of Health and the Patient-Centered Outcomes Research Institute.

The American Gastroenterological Association recently issued a clinical practice update expert review outlining tenets of high-quality colonoscopy screening and surveillance.

The update includes 15 best practice advice statements aimed at the endoscopist and/or endoscopy unit, reported lead author Rajesh N. Keswani, MD, of Northwestern University, Chicago, and colleagues.

“The efficacy of colonoscopy varies widely among endoscopists, and lower-quality colonoscopies are associated with higher interval CRC [colorectal cancer] incidence and mortality,” the investigators wrote in Gastroenterology.

According to Dr. Keswani and colleagues, quality of colonoscopy screening and surveillance is shaped by three parameters: safety, effectiveness, and value. Some metrics may be best measured at a unit level, they noted, while others are more clinician specific.

“For uncommon outcomes (e.g., adverse events) or metrics that reflect system-based practice (e.g., bowel preparation quality), measurement of aggregate unit-level performance is best,” the investigators wrote. “In contrast, for metrics that primarily reflect colonoscopist skill (e.g., adenoma detection rate), endoscopist-level measurement is preferred to enable individual feedback.”
 

Endoscopy unit best practice advice

According to the update, endoscopy units should prepare patients for, and monitor, adverse events. Prior to the procedure, patients should be informed about possible adverse events and warning symptoms, and emergency contact information should be recorded. Following the procedure, systematic monitoring of delayed adverse events may be considered, including “postprocedure bleeding, perforation, hospital readmission, 30-day mortality, and/or interval colorectal cancer cases,” with rates reported at the unit level.

Ensuring high-quality bowel preparation is also the responsibility of the endoscopy unit, according to Dr. Keswani and colleagues, and should be measured at least annually. Units should aim for a Boston Bowel Preparation Scale score of at least 6, with each segment scoring at least 2, in at least 90% of colonoscopies. The update provides best practice advice on split-dose bowel prep, with patient instructions written at a sixth-grade level in their native language. If routine quality measurement reveals suboptimal bowel prep quality, instruction revision may be needed, as well as further patient education and support.

During the actual procedure, a high-definition colonoscope should be used, the expert panel wrote. They called for measurement of endoscopist performance via four parameters: cecal intubation rate, which should be at least 90%; mean withdrawal time, which should be at least 6 minutes (aspirational, ≥9 minutes); adenoma detection rate, measured annually or when a given endoscopist has accrued 250 screening colonoscopies; and serrated lesion detection rate.
 

Endoscopist best practice advice

Both adenoma detection rate and serrated lesion detection rate should also be measured at an endoscopist level, with rates of at least 30% for adenomas and at least 7% for serrated lesions (aspirational, ≥35% and ≥10%, respectively).

“If rates are low, improvement efforts should be oriented toward both colonoscopists and pathologists,” the investigators noted.

A variety of strategies are advised to improve outcomes at the endoscopist level, including a second look at the right colon to detect polyps, either in forward or retroflexed view; use of cold-snare polypectomy for nonpedunculated polyps 3-9 mm in size and avoidance of forceps in polyps greater than 2 mm in size; evaluation by an expert in polypectomy with attempted resection for patients with complex polyps lacking “overt malignant endoscopic features or pathology consistent with invasive adenocarcinoma”; and thorough documentation of all findings.

More broadly, the update advises endoscopists to follow guideline-recommended intervals for screening and surveillance, including repeat colonoscopy in 3 years for all patients with advanced adenomas versus a 10-year interval for patients with normal risk or “only distal hyperplastic polyps.”
 

Resource-limited institutions and a look ahead

Dr. Keswani and colleagues concluded the clinical practice update with a nod to the challenges of real-world practice, noting that some institutions may not have the resources to comply with all the best practice advice statements.

“If limited resources are available, measurement of cecal intubation rates, bowel preparation quality, and adenoma detection rate should be prioritized,” they wrote.

They also offered a succinct summary of outstanding research needs, saying “we anticipate future work to clarify optimal polyp resection techniques, refine surveillance intervals based on provider skill and patient risk, and highlight the benefits of artificial intelligence in improving colonoscopy quality.”

This clinical practice update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board. Dr. Keswani consults for Boston Scientific. The other authors had no disclosures.

This article was updated Aug. 20, 2021.

The American Gastroenterological Association recently issued a clinical practice update expert review outlining tenets of high-quality colonoscopy screening and surveillance.

The update includes 15 best practice advice statements aimed at the endoscopist and/or endoscopy unit, reported lead author Rajesh N. Keswani, MD, of Northwestern University, Chicago, and colleagues.

“The efficacy of colonoscopy varies widely among endoscopists, and lower-quality colonoscopies are associated with higher interval CRC [colorectal cancer] incidence and mortality,” the investigators wrote in Gastroenterology.

According to Dr. Keswani and colleagues, quality of colonoscopy screening and surveillance is shaped by three parameters: safety, effectiveness, and value. Some metrics may be best measured at a unit level, they noted, while others are more clinician specific.

“For uncommon outcomes (e.g., adverse events) or metrics that reflect system-based practice (e.g., bowel preparation quality), measurement of aggregate unit-level performance is best,” the investigators wrote. “In contrast, for metrics that primarily reflect colonoscopist skill (e.g., adenoma detection rate), endoscopist-level measurement is preferred to enable individual feedback.”
 

Endoscopy unit best practice advice

According to the update, endoscopy units should prepare patients for, and monitor, adverse events. Prior to the procedure, patients should be informed about possible adverse events and warning symptoms, and emergency contact information should be recorded. Following the procedure, systematic monitoring of delayed adverse events may be considered, including “postprocedure bleeding, perforation, hospital readmission, 30-day mortality, and/or interval colorectal cancer cases,” with rates reported at the unit level.

Ensuring high-quality bowel preparation is also the responsibility of the endoscopy unit, according to Dr. Keswani and colleagues, and should be measured at least annually. Units should aim for a Boston Bowel Preparation Scale score of at least 6, with each segment scoring at least 2, in at least 90% of colonoscopies. The update provides best practice advice on split-dose bowel prep, with patient instructions written at a sixth-grade level in their native language. If routine quality measurement reveals suboptimal bowel prep quality, instruction revision may be needed, as well as further patient education and support.

During the actual procedure, a high-definition colonoscope should be used, the expert panel wrote. They called for measurement of endoscopist performance via four parameters: cecal intubation rate, which should be at least 90%; mean withdrawal time, which should be at least 6 minutes (aspirational, ≥9 minutes); adenoma detection rate, measured annually or when a given endoscopist has accrued 250 screening colonoscopies; and serrated lesion detection rate.
 

Endoscopist best practice advice

Both adenoma detection rate and serrated lesion detection rate should also be measured at an endoscopist level, with rates of at least 30% for adenomas and at least 7% for serrated lesions (aspirational, ≥35% and ≥10%, respectively).

“If rates are low, improvement efforts should be oriented toward both colonoscopists and pathologists,” the investigators noted.

A variety of strategies are advised to improve outcomes at the endoscopist level, including a second look at the right colon to detect polyps, either in forward or retroflexed view; use of cold-snare polypectomy for nonpedunculated polyps 3-9 mm in size and avoidance of forceps in polyps greater than 2 mm in size; evaluation by an expert in polypectomy with attempted resection for patients with complex polyps lacking “overt malignant endoscopic features or pathology consistent with invasive adenocarcinoma”; and thorough documentation of all findings.

More broadly, the update advises endoscopists to follow guideline-recommended intervals for screening and surveillance, including repeat colonoscopy in 3 years for all patients with advanced adenomas versus a 10-year interval for patients with normal risk or “only distal hyperplastic polyps.”
 

Resource-limited institutions and a look ahead

Dr. Keswani and colleagues concluded the clinical practice update with a nod to the challenges of real-world practice, noting that some institutions may not have the resources to comply with all the best practice advice statements.

“If limited resources are available, measurement of cecal intubation rates, bowel preparation quality, and adenoma detection rate should be prioritized,” they wrote.

They also offered a succinct summary of outstanding research needs, saying “we anticipate future work to clarify optimal polyp resection techniques, refine surveillance intervals based on provider skill and patient risk, and highlight the benefits of artificial intelligence in improving colonoscopy quality.”

This clinical practice update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board. Dr. Keswani consults for Boston Scientific. The other authors had no disclosures.

This article was updated Aug. 20, 2021.

The American Gastroenterological Association recently issued a clinical practice update expert review outlining tenets of high-quality colonoscopy screening and surveillance.

The update includes 15 best practice advice statements aimed at the endoscopist and/or endoscopy unit, reported lead author Rajesh N. Keswani, MD, of Northwestern University, Chicago, and colleagues.

“The efficacy of colonoscopy varies widely among endoscopists, and lower-quality colonoscopies are associated with higher interval CRC [colorectal cancer] incidence and mortality,” the investigators wrote in Gastroenterology.

According to Dr. Keswani and colleagues, quality of colonoscopy screening and surveillance is shaped by three parameters: safety, effectiveness, and value. Some metrics may be best measured at a unit level, they noted, while others are more clinician specific.

“For uncommon outcomes (e.g., adverse events) or metrics that reflect system-based practice (e.g., bowel preparation quality), measurement of aggregate unit-level performance is best,” the investigators wrote. “In contrast, for metrics that primarily reflect colonoscopist skill (e.g., adenoma detection rate), endoscopist-level measurement is preferred to enable individual feedback.”
 

Endoscopy unit best practice advice

According to the update, endoscopy units should prepare patients for, and monitor, adverse events. Prior to the procedure, patients should be informed about possible adverse events and warning symptoms, and emergency contact information should be recorded. Following the procedure, systematic monitoring of delayed adverse events may be considered, including “postprocedure bleeding, perforation, hospital readmission, 30-day mortality, and/or interval colorectal cancer cases,” with rates reported at the unit level.

Ensuring high-quality bowel preparation is also the responsibility of the endoscopy unit, according to Dr. Keswani and colleagues, and should be measured at least annually. Units should aim for a Boston Bowel Preparation Scale score of at least 6, with each segment scoring at least 2, in at least 90% of colonoscopies. The update provides best practice advice on split-dose bowel prep, with patient instructions written at a sixth-grade level in their native language. If routine quality measurement reveals suboptimal bowel prep quality, instruction revision may be needed, as well as further patient education and support.

During the actual procedure, a high-definition colonoscope should be used, the expert panel wrote. They called for measurement of endoscopist performance via four parameters: cecal intubation rate, which should be at least 90%; mean withdrawal time, which should be at least 6 minutes (aspirational, ≥9 minutes); adenoma detection rate, measured annually or when a given endoscopist has accrued 250 screening colonoscopies; and serrated lesion detection rate.
 

Endoscopist best practice advice

Both adenoma detection rate and serrated lesion detection rate should also be measured at an endoscopist level, with rates of at least 30% for adenomas and at least 7% for serrated lesions (aspirational, ≥35% and ≥10%, respectively).

“If rates are low, improvement efforts should be oriented toward both colonoscopists and pathologists,” the investigators noted.

A variety of strategies are advised to improve outcomes at the endoscopist level, including a second look at the right colon to detect polyps, either in forward or retroflexed view; use of cold-snare polypectomy for nonpedunculated polyps 3-9 mm in size and avoidance of forceps in polyps greater than 2 mm in size; evaluation by an expert in polypectomy with attempted resection for patients with complex polyps lacking “overt malignant endoscopic features or pathology consistent with invasive adenocarcinoma”; and thorough documentation of all findings.

More broadly, the update advises endoscopists to follow guideline-recommended intervals for screening and surveillance, including repeat colonoscopy in 3 years for all patients with advanced adenomas versus a 10-year interval for patients with normal risk or “only distal hyperplastic polyps.”
 

Resource-limited institutions and a look ahead

Dr. Keswani and colleagues concluded the clinical practice update with a nod to the challenges of real-world practice, noting that some institutions may not have the resources to comply with all the best practice advice statements.

“If limited resources are available, measurement of cecal intubation rates, bowel preparation quality, and adenoma detection rate should be prioritized,” they wrote.

They also offered a succinct summary of outstanding research needs, saying “we anticipate future work to clarify optimal polyp resection techniques, refine surveillance intervals based on provider skill and patient risk, and highlight the benefits of artificial intelligence in improving colonoscopy quality.”

This clinical practice update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board. Dr. Keswani consults for Boston Scientific. The other authors had no disclosures.

This article was updated Aug. 20, 2021.

Asymptomatic pregnant women with no previous diagnosis of type 1 or 2 diabetes should be screened for gestational diabetes at 24 weeks’ gestation or later, according to an updated recommendation from the U.S. Preventive Services Task Force.

Pregnant individuals who develop gestational diabetes are at increased risk for complications including preeclampsia, fetal macrosomia, and neonatal hypoglycemia, as well as negative long-term outcomes for themselves and their children, wrote lead author Karina W. Davidson, PhD, of Feinstein Institute for Medical Research, Manhasset, N.Y., and colleagues. The statement was published online in JAMA.

The B recommendation and I statement reflect “moderate certainty” that current evidence supports the recommendation in terms of harms versus benefits, and is consistent with the 2014 USPSTF recommendation.

The statement calls for a one-time screening using a glucose tolerance test at or after 24 weeks’ gestation. Although most screening in the United States takes place prior to 28 weeks’ gestation, it can be performed later in patients who begin prenatal care after 28 weeks’ gestation, according to the statement. Data on the harms and benefits of gestational diabetes screening prior to 24 weeks’ gestation are limited, the authors noted. Gestational diabetes was defined as diabetes that develops during pregnancy that is not clearly overt diabetes.

To update the 2014 recommendation, the USPSTF commissioned a systematic review. In 45 prospective studies on the accuracy of gestational diabetes screening, several tests, included oral glucose challenge test, oral glucose tolerance test, and fasting plasma glucose using either a one- or two-step approach were accurate detectors of gestational diabetes; therefore, the USPSTF does not recommend a specific test.

In 13 trials on the impact of treating gestational diabetes on intermediate and health outcomes, treatment was associated with a reduced risk of outcomes, including primary cesarean delivery (but not total cesarean delivery) and preterm delivery, but not with a reduced risk of outcomes including preeclampsia, emergency cesarean delivery, induction of labor, or maternal birth trauma.

The task force also reviewed seven studies of harms associated with screening for gestational diabetes, including three on psychosocial harms, three on hospital experiences, and one of the odds of cesarean delivery after a diagnosis of gestational diabetes. No increase in anxiety or depression occurred following a positive diagnosis or false-positive test result, but data suggested that a gestational diabetes diagnosis may be associated with higher rates of cesarean delivery.

A total of 13 trials evaluated the harms associated with treatment of gestational diabetes, and found no association between treatment and increased risk of several outcomes including severe maternal hypoglycemia, low birth weight, and small for gestational age, and no effect was noted on the number of cesarean deliveries.

Evidence gaps that require additional research include randomized, controlled trials on the effects of gestational diabetes screening on health outcomes, as well as benefits versus harms of screening for pregnant individuals prior to 24 weeks, and studies on the effects of screening in subpopulations of race/ethnicity, age, and socioeconomic factors, according to the task force. Additional research also is needed in areas of maternal health outcomes, long-term outcomes, and the effect on outcomes of one-step versus two-step screening, the USPSTF said.

However, “screening for and detecting gestational diabetes provides a potential opportunity to control blood glucose levels (through lifestyle changes, pharmacological interventions, or both) and reduce the risk of macrosomia and LGA [large for gestational age] infants,” the task force wrote. “In turn, this can prevent associated complications such as primary cesarean delivery, shoulder dystocia, and [neonatal] ICU admissions.”
 

Support screening with counseling on risk reduction

The USPSTF recommendation is important at this time because “the prevalence of gestational diabetes is increasing secondary to rising rates of obesity,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview.

“In 2014, based on a systematic review of literature, the USPSTF recommended screening all asymptomatic pregnant women for gestational diabetes mellitus [GDM] starting at 24 weeks’ gestation. The recommended gestational age for screening coincides with increasing insulin resistance during pregnancy with advancing gestational age,” Dr. Krishna said.

“An updated systematic review by the USPSTF concluded that existing literature continues to affirm current recommendations of universal screening for GDM at 24 weeks gestation or later. There continues, however, to be no consensus on the optimal approach to screening,” she noted.

“Screening can be performed as a two-step or one-step approach,” said Dr. Krishna. “The two-step approach is commonly used in the United States, and all pregnant women are first screened with a 50-gram oral glucose solution followed by a diagnostic test if they have a positive initial screening.

“Women with risk factors for diabetes, such as prior GDM, obesity, strong family history of diabetes, or history of fetal macrosomia, should be screened early in pregnancy for GDM and have the GDM screen repeated at 24 weeks’ gestation or later if normal in early pregnancy,” Dr. Krishna said. “Pregnant women should be counseled on the importance of diet and exercise and appropriate weight gain in pregnancy to reduce the risk of GDM. Overall, timely diagnosis of gestational diabetes is crucial to improving maternal and fetal pregnancy outcomes.”

The full recommendation statement is also available on the USPSTF website. The research was supported by the Agency for Healthcare Research and Quality. The researchers had no financial conflicts to disclose. Dr. Krishna had no disclosures, but serves on the editorial advisory board of Ob.Gyn News.

Asymptomatic pregnant women with no previous diagnosis of type 1 or 2 diabetes should be screened for gestational diabetes at 24 weeks’ gestation or later, according to an updated recommendation from the U.S. Preventive Services Task Force.

Pregnant individuals who develop gestational diabetes are at increased risk for complications including preeclampsia, fetal macrosomia, and neonatal hypoglycemia, as well as negative long-term outcomes for themselves and their children, wrote lead author Karina W. Davidson, PhD, of Feinstein Institute for Medical Research, Manhasset, N.Y., and colleagues. The statement was published online in JAMA.

The B recommendation and I statement reflect “moderate certainty” that current evidence supports the recommendation in terms of harms versus benefits, and is consistent with the 2014 USPSTF recommendation.

The statement calls for a one-time screening using a glucose tolerance test at or after 24 weeks’ gestation. Although most screening in the United States takes place prior to 28 weeks’ gestation, it can be performed later in patients who begin prenatal care after 28 weeks’ gestation, according to the statement. Data on the harms and benefits of gestational diabetes screening prior to 24 weeks’ gestation are limited, the authors noted. Gestational diabetes was defined as diabetes that develops during pregnancy that is not clearly overt diabetes.

To update the 2014 recommendation, the USPSTF commissioned a systematic review. In 45 prospective studies on the accuracy of gestational diabetes screening, several tests, included oral glucose challenge test, oral glucose tolerance test, and fasting plasma glucose using either a one- or two-step approach were accurate detectors of gestational diabetes; therefore, the USPSTF does not recommend a specific test.

In 13 trials on the impact of treating gestational diabetes on intermediate and health outcomes, treatment was associated with a reduced risk of outcomes, including primary cesarean delivery (but not total cesarean delivery) and preterm delivery, but not with a reduced risk of outcomes including preeclampsia, emergency cesarean delivery, induction of labor, or maternal birth trauma.

The task force also reviewed seven studies of harms associated with screening for gestational diabetes, including three on psychosocial harms, three on hospital experiences, and one of the odds of cesarean delivery after a diagnosis of gestational diabetes. No increase in anxiety or depression occurred following a positive diagnosis or false-positive test result, but data suggested that a gestational diabetes diagnosis may be associated with higher rates of cesarean delivery.

A total of 13 trials evaluated the harms associated with treatment of gestational diabetes, and found no association between treatment and increased risk of several outcomes including severe maternal hypoglycemia, low birth weight, and small for gestational age, and no effect was noted on the number of cesarean deliveries.

Evidence gaps that require additional research include randomized, controlled trials on the effects of gestational diabetes screening on health outcomes, as well as benefits versus harms of screening for pregnant individuals prior to 24 weeks, and studies on the effects of screening in subpopulations of race/ethnicity, age, and socioeconomic factors, according to the task force. Additional research also is needed in areas of maternal health outcomes, long-term outcomes, and the effect on outcomes of one-step versus two-step screening, the USPSTF said.

However, “screening for and detecting gestational diabetes provides a potential opportunity to control blood glucose levels (through lifestyle changes, pharmacological interventions, or both) and reduce the risk of macrosomia and LGA [large for gestational age] infants,” the task force wrote. “In turn, this can prevent associated complications such as primary cesarean delivery, shoulder dystocia, and [neonatal] ICU admissions.”
 

Support screening with counseling on risk reduction

The USPSTF recommendation is important at this time because “the prevalence of gestational diabetes is increasing secondary to rising rates of obesity,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview.

“In 2014, based on a systematic review of literature, the USPSTF recommended screening all asymptomatic pregnant women for gestational diabetes mellitus [GDM] starting at 24 weeks’ gestation. The recommended gestational age for screening coincides with increasing insulin resistance during pregnancy with advancing gestational age,” Dr. Krishna said.

“An updated systematic review by the USPSTF concluded that existing literature continues to affirm current recommendations of universal screening for GDM at 24 weeks gestation or later. There continues, however, to be no consensus on the optimal approach to screening,” she noted.

“Screening can be performed as a two-step or one-step approach,” said Dr. Krishna. “The two-step approach is commonly used in the United States, and all pregnant women are first screened with a 50-gram oral glucose solution followed by a diagnostic test if they have a positive initial screening.

“Women with risk factors for diabetes, such as prior GDM, obesity, strong family history of diabetes, or history of fetal macrosomia, should be screened early in pregnancy for GDM and have the GDM screen repeated at 24 weeks’ gestation or later if normal in early pregnancy,” Dr. Krishna said. “Pregnant women should be counseled on the importance of diet and exercise and appropriate weight gain in pregnancy to reduce the risk of GDM. Overall, timely diagnosis of gestational diabetes is crucial to improving maternal and fetal pregnancy outcomes.”

The full recommendation statement is also available on the USPSTF website. The research was supported by the Agency for Healthcare Research and Quality. The researchers had no financial conflicts to disclose. Dr. Krishna had no disclosures, but serves on the editorial advisory board of Ob.Gyn News.

Asymptomatic pregnant women with no previous diagnosis of type 1 or 2 diabetes should be screened for gestational diabetes at 24 weeks’ gestation or later, according to an updated recommendation from the U.S. Preventive Services Task Force.

Pregnant individuals who develop gestational diabetes are at increased risk for complications including preeclampsia, fetal macrosomia, and neonatal hypoglycemia, as well as negative long-term outcomes for themselves and their children, wrote lead author Karina W. Davidson, PhD, of Feinstein Institute for Medical Research, Manhasset, N.Y., and colleagues. The statement was published online in JAMA.

The B recommendation and I statement reflect “moderate certainty” that current evidence supports the recommendation in terms of harms versus benefits, and is consistent with the 2014 USPSTF recommendation.

The statement calls for a one-time screening using a glucose tolerance test at or after 24 weeks’ gestation. Although most screening in the United States takes place prior to 28 weeks’ gestation, it can be performed later in patients who begin prenatal care after 28 weeks’ gestation, according to the statement. Data on the harms and benefits of gestational diabetes screening prior to 24 weeks’ gestation are limited, the authors noted. Gestational diabetes was defined as diabetes that develops during pregnancy that is not clearly overt diabetes.

To update the 2014 recommendation, the USPSTF commissioned a systematic review. In 45 prospective studies on the accuracy of gestational diabetes screening, several tests, included oral glucose challenge test, oral glucose tolerance test, and fasting plasma glucose using either a one- or two-step approach were accurate detectors of gestational diabetes; therefore, the USPSTF does not recommend a specific test.

In 13 trials on the impact of treating gestational diabetes on intermediate and health outcomes, treatment was associated with a reduced risk of outcomes, including primary cesarean delivery (but not total cesarean delivery) and preterm delivery, but not with a reduced risk of outcomes including preeclampsia, emergency cesarean delivery, induction of labor, or maternal birth trauma.

The task force also reviewed seven studies of harms associated with screening for gestational diabetes, including three on psychosocial harms, three on hospital experiences, and one of the odds of cesarean delivery after a diagnosis of gestational diabetes. No increase in anxiety or depression occurred following a positive diagnosis or false-positive test result, but data suggested that a gestational diabetes diagnosis may be associated with higher rates of cesarean delivery.

A total of 13 trials evaluated the harms associated with treatment of gestational diabetes, and found no association between treatment and increased risk of several outcomes including severe maternal hypoglycemia, low birth weight, and small for gestational age, and no effect was noted on the number of cesarean deliveries.

Evidence gaps that require additional research include randomized, controlled trials on the effects of gestational diabetes screening on health outcomes, as well as benefits versus harms of screening for pregnant individuals prior to 24 weeks, and studies on the effects of screening in subpopulations of race/ethnicity, age, and socioeconomic factors, according to the task force. Additional research also is needed in areas of maternal health outcomes, long-term outcomes, and the effect on outcomes of one-step versus two-step screening, the USPSTF said.

However, “screening for and detecting gestational diabetes provides a potential opportunity to control blood glucose levels (through lifestyle changes, pharmacological interventions, or both) and reduce the risk of macrosomia and LGA [large for gestational age] infants,” the task force wrote. “In turn, this can prevent associated complications such as primary cesarean delivery, shoulder dystocia, and [neonatal] ICU admissions.”
 

Support screening with counseling on risk reduction

The USPSTF recommendation is important at this time because “the prevalence of gestational diabetes is increasing secondary to rising rates of obesity,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview.

“In 2014, based on a systematic review of literature, the USPSTF recommended screening all asymptomatic pregnant women for gestational diabetes mellitus [GDM] starting at 24 weeks’ gestation. The recommended gestational age for screening coincides with increasing insulin resistance during pregnancy with advancing gestational age,” Dr. Krishna said.

“An updated systematic review by the USPSTF concluded that existing literature continues to affirm current recommendations of universal screening for GDM at 24 weeks gestation or later. There continues, however, to be no consensus on the optimal approach to screening,” she noted.

“Screening can be performed as a two-step or one-step approach,” said Dr. Krishna. “The two-step approach is commonly used in the United States, and all pregnant women are first screened with a 50-gram oral glucose solution followed by a diagnostic test if they have a positive initial screening.

“Women with risk factors for diabetes, such as prior GDM, obesity, strong family history of diabetes, or history of fetal macrosomia, should be screened early in pregnancy for GDM and have the GDM screen repeated at 24 weeks’ gestation or later if normal in early pregnancy,” Dr. Krishna said. “Pregnant women should be counseled on the importance of diet and exercise and appropriate weight gain in pregnancy to reduce the risk of GDM. Overall, timely diagnosis of gestational diabetes is crucial to improving maternal and fetal pregnancy outcomes.”

The full recommendation statement is also available on the USPSTF website. The research was supported by the Agency for Healthcare Research and Quality. The researchers had no financial conflicts to disclose. Dr. Krishna had no disclosures, but serves on the editorial advisory board of Ob.Gyn News.

The American Gastroenterological Association published a clinical practice update expert review for managing malignant alimentary tract obstructions (MATOs) that includes 14 best practice advice statements, ranging from general principles to specific clinical choices.

“There are many options available for the management of MATOs, with the addition of new modalities as interventional endoscopy continues to evolve,” Osman Ahmed, MD, of the University of Toronto and colleagues wrote in Clinical Gastroenterology and Hepatology. “The important concept to understand for any physician managing MATOs is that there is no longer a ‘one-size-fits-all’ approach that can be applied to all patients.”

First, the investigators called for an individualized, multidisciplinary approach that includes oncologists, surgeons, and endoscopists. They advised physicians to “take into account the characteristics of the obstruction, patient’s expectations, prognosis, expected subsequent therapies, and functional status.”

The remaining advice statements are organized by site of obstruction, with various management approaches based on candidacy for resection and other patient factors.
 

Esophageal obstruction

For patients with esophageal obstruction who are candidates for resection or chemoradiation, Dr. Ahmed and colleagues advised against routine use of self-expanding metal stents (SEMS) due to “high rates of stent migration, higher morbidity and mortality, and potentially lower R0 (microscopically negative margins) resection rates.”

If such patients are at risk of malnutrition, an enteral feeding tube may be considered, although patients should be counseled about associated procedural risks, such as abdominal wall tumor seeding.

Among patients with esophageal obstruction who are not candidates for resection, SEMS insertion or brachytherapy may be used separately or in combination, according to the investigators.

“Clinicians should not consider the use of laser therapy or photodynamic therapy because of the lack of evidence of better outcomes and superior alternatives,” the investigators noted.

If SEMS placement is elected, Dr. Ahmed and colleagues noted there remains ongoing debate. For this expert review, the authors advised using a fully covered stent, based on potentially higher risk for tumor ingrowth and reinterventions with uncovered SEMS.
 

Gastric outlet obstruction

According to the update, patients with gastric outlet obstruction who have good functional status and a life expectancy greater than 2 months should undergo surgical gastrojejunostomy, ideally via a laparoscopic approach instead of an open approach because of shorter hospital stays and less blood loss. If a sufficiently experienced endoscopist is available, an endoscopic ultrasound-guided gastrojejunostomy may be performed, although Dr. Ahmed and colleagues noted that no devices have been approved by the Food and Drug Administration for this technique.

For patients who are not candidates for gastrojejunostomy, enteral stent insertion should be considered; however, they should not be used in patients with severely impaired gastric motility or multiple luminal obstructions “because of limited benefit in these scenarios.” Instead, a venting gastrostomy may be elected.
 

Colonic obstruction

For patients with malignant colonic obstruction, SEMS may be considered as a “bridge to surgery,” wrote Dr. Ahmed and colleagues, and in the case of proximal or right-sided malignant obstruction, as a bridge to surgery or a palliative measure, keeping in mind “the technical challenges of SEMS insertion in those areas.”

Extracolonic obstruction

Finally, the expert panel suggested that SEMS may be appropriate for selective extracolonic malignancy if patients are not surgical candidates, noting that SEMS placement in this scenario “is more technically challenging, clinical success rates are more variable, and complications (including stent migration) are more frequent.”

The investigators concluded by advising clinicians to remain within the realm of their abilities when managing MATOs, and to refer when needed.

“[I]t is important for physicians to understand their limits and expertise and recognize when cases are best managed at experienced high-volume centers,” they wrote.

The clinical practice update expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board. Dr. Lee disclosed a relationship with Boston Scientific.

The American Gastroenterological Association published a clinical practice update expert review for managing malignant alimentary tract obstructions (MATOs) that includes 14 best practice advice statements, ranging from general principles to specific clinical choices.

“There are many options available for the management of MATOs, with the addition of new modalities as interventional endoscopy continues to evolve,” Osman Ahmed, MD, of the University of Toronto and colleagues wrote in Clinical Gastroenterology and Hepatology. “The important concept to understand for any physician managing MATOs is that there is no longer a ‘one-size-fits-all’ approach that can be applied to all patients.”

First, the investigators called for an individualized, multidisciplinary approach that includes oncologists, surgeons, and endoscopists. They advised physicians to “take into account the characteristics of the obstruction, patient’s expectations, prognosis, expected subsequent therapies, and functional status.”

The remaining advice statements are organized by site of obstruction, with various management approaches based on candidacy for resection and other patient factors.
 

Esophageal obstruction

For patients with esophageal obstruction who are candidates for resection or chemoradiation, Dr. Ahmed and colleagues advised against routine use of self-expanding metal stents (SEMS) due to “high rates of stent migration, higher morbidity and mortality, and potentially lower R0 (microscopically negative margins) resection rates.”

If such patients are at risk of malnutrition, an enteral feeding tube may be considered, although patients should be counseled about associated procedural risks, such as abdominal wall tumor seeding.

Among patients with esophageal obstruction who are not candidates for resection, SEMS insertion or brachytherapy may be used separately or in combination, according to the investigators.

“Clinicians should not consider the use of laser therapy or photodynamic therapy because of the lack of evidence of better outcomes and superior alternatives,” the investigators noted.

If SEMS placement is elected, Dr. Ahmed and colleagues noted there remains ongoing debate. For this expert review, the authors advised using a fully covered stent, based on potentially higher risk for tumor ingrowth and reinterventions with uncovered SEMS.
 

Gastric outlet obstruction

According to the update, patients with gastric outlet obstruction who have good functional status and a life expectancy greater than 2 months should undergo surgical gastrojejunostomy, ideally via a laparoscopic approach instead of an open approach because of shorter hospital stays and less blood loss. If a sufficiently experienced endoscopist is available, an endoscopic ultrasound-guided gastrojejunostomy may be performed, although Dr. Ahmed and colleagues noted that no devices have been approved by the Food and Drug Administration for this technique.

For patients who are not candidates for gastrojejunostomy, enteral stent insertion should be considered; however, they should not be used in patients with severely impaired gastric motility or multiple luminal obstructions “because of limited benefit in these scenarios.” Instead, a venting gastrostomy may be elected.
 

Colonic obstruction

For patients with malignant colonic obstruction, SEMS may be considered as a “bridge to surgery,” wrote Dr. Ahmed and colleagues, and in the case of proximal or right-sided malignant obstruction, as a bridge to surgery or a palliative measure, keeping in mind “the technical challenges of SEMS insertion in those areas.”

Extracolonic obstruction

Finally, the expert panel suggested that SEMS may be appropriate for selective extracolonic malignancy if patients are not surgical candidates, noting that SEMS placement in this scenario “is more technically challenging, clinical success rates are more variable, and complications (including stent migration) are more frequent.”

The investigators concluded by advising clinicians to remain within the realm of their abilities when managing MATOs, and to refer when needed.

“[I]t is important for physicians to understand their limits and expertise and recognize when cases are best managed at experienced high-volume centers,” they wrote.

The clinical practice update expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board. Dr. Lee disclosed a relationship with Boston Scientific.

The American Gastroenterological Association published a clinical practice update expert review for managing malignant alimentary tract obstructions (MATOs) that includes 14 best practice advice statements, ranging from general principles to specific clinical choices.

“There are many options available for the management of MATOs, with the addition of new modalities as interventional endoscopy continues to evolve,” Osman Ahmed, MD, of the University of Toronto and colleagues wrote in Clinical Gastroenterology and Hepatology. “The important concept to understand for any physician managing MATOs is that there is no longer a ‘one-size-fits-all’ approach that can be applied to all patients.”

First, the investigators called for an individualized, multidisciplinary approach that includes oncologists, surgeons, and endoscopists. They advised physicians to “take into account the characteristics of the obstruction, patient’s expectations, prognosis, expected subsequent therapies, and functional status.”

The remaining advice statements are organized by site of obstruction, with various management approaches based on candidacy for resection and other patient factors.
 

Esophageal obstruction

For patients with esophageal obstruction who are candidates for resection or chemoradiation, Dr. Ahmed and colleagues advised against routine use of self-expanding metal stents (SEMS) due to “high rates of stent migration, higher morbidity and mortality, and potentially lower R0 (microscopically negative margins) resection rates.”

If such patients are at risk of malnutrition, an enteral feeding tube may be considered, although patients should be counseled about associated procedural risks, such as abdominal wall tumor seeding.

Among patients with esophageal obstruction who are not candidates for resection, SEMS insertion or brachytherapy may be used separately or in combination, according to the investigators.

“Clinicians should not consider the use of laser therapy or photodynamic therapy because of the lack of evidence of better outcomes and superior alternatives,” the investigators noted.

If SEMS placement is elected, Dr. Ahmed and colleagues noted there remains ongoing debate. For this expert review, the authors advised using a fully covered stent, based on potentially higher risk for tumor ingrowth and reinterventions with uncovered SEMS.
 

Gastric outlet obstruction

According to the update, patients with gastric outlet obstruction who have good functional status and a life expectancy greater than 2 months should undergo surgical gastrojejunostomy, ideally via a laparoscopic approach instead of an open approach because of shorter hospital stays and less blood loss. If a sufficiently experienced endoscopist is available, an endoscopic ultrasound-guided gastrojejunostomy may be performed, although Dr. Ahmed and colleagues noted that no devices have been approved by the Food and Drug Administration for this technique.

For patients who are not candidates for gastrojejunostomy, enteral stent insertion should be considered; however, they should not be used in patients with severely impaired gastric motility or multiple luminal obstructions “because of limited benefit in these scenarios.” Instead, a venting gastrostomy may be elected.
 

Colonic obstruction

For patients with malignant colonic obstruction, SEMS may be considered as a “bridge to surgery,” wrote Dr. Ahmed and colleagues, and in the case of proximal or right-sided malignant obstruction, as a bridge to surgery or a palliative measure, keeping in mind “the technical challenges of SEMS insertion in those areas.”

Extracolonic obstruction

Finally, the expert panel suggested that SEMS may be appropriate for selective extracolonic malignancy if patients are not surgical candidates, noting that SEMS placement in this scenario “is more technically challenging, clinical success rates are more variable, and complications (including stent migration) are more frequent.”

The investigators concluded by advising clinicians to remain within the realm of their abilities when managing MATOs, and to refer when needed.

“[I]t is important for physicians to understand their limits and expertise and recognize when cases are best managed at experienced high-volume centers,” they wrote.

The clinical practice update expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board. Dr. Lee disclosed a relationship with Boston Scientific.

Today there are so many evidence-based drug therapies for heart failure with reduced ejection fraction (HFrEF) that physicians treating HF patients almost don’t know what to do them.

It’s an exciting new age that way, but to many vexingly unclear how best to merge the shiny new options with mainstay regimens based on time-honored renin-angiotensin system (RAS) inhibitors and beta-blockers.

To impart some clarity, the authors of a new HF guideline document recently took center stage at the Heart Failure Association of the European Society of Cardiology (ESC-HFA) annual meeting to preview their updated recommendations, with novel twists based on recent major trials, for the new age of HF pharmacotherapeutics.

The guideline committee considered the evidence base that existed “up until the end of March of this year,” Theresa A. McDonagh, MD, King’s College London, said during the presentation. The document “is now finalized, it’s with the publishers, and it will be presented in full with simultaneous publication at the ESC meeting” that starts August 27.

It describes a game plan, already followed by some clinicians in practice without official guidance, for initiating drugs from each of four classes in virtually all patients with HFrEF.
 

New indicated drugs, new perspective for HFrEF

Three of the drug categories are old acquaintances. Among them are the RAS inhibitors, which include angiotensin-receptor/neprilysin inhibitors, beta-blockers, and the mineralocorticoid receptor antagonists. The latter drugs are gaining new respect after having been underplayed in HF prescribing despite longstanding evidence of efficacy.

Completing the quartet of first-line HFrEF drug classes is a recent arrival to the HF arena, the sodium-glucose cotransporter 2 inhibitors.

“We now have new data and a simplified treatment algorithm for heart failure with reduced ejection fraction based on the early administration of the four major classes of drugs,” said Marco Metra, MD, University of Brescia (Italy), previewing the medical-therapy portions of the new guideline at the ESC-HFA sessions, which launched virtually and live in Florence, Italy, on July 29.

The new game plan offers a simple answer to a once-common but complex question: How and in what order are the different drug classes initiated in patients with HFrEF? In the new document, the stated goal is to get them all on board expeditiously and safely, by any means possible.

The guideline writers did not specify a sequence, preferring to leave that decision to physicians, said Dr. Metra, who stated only two guiding principles. The first is to consider the patient’s unique circumstances. The order in which the drugs are introduced might vary, depending on, for example, whether the patient has low or high blood pressure or renal dysfunction.

Second, “it is very important that we try to give all four classes of drugs to the patient in the shortest time possible, because this saves lives,” he said.

That there is no recommendation on sequencing the drugs has led some to the wrong interpretation that all should be started at once, observed coauthor Javed Butler, MD, MPH, University of Mississippi, Jackson, as a panelist during the presentation. Far from it, he said. “The doctor with the patient in front of you can make the best decision. The idea here is to get all the therapies on as soon as possible, as safely as possible.”

“The order in which they are introduced is not really important,” agreed Vijay Chopra, MD, Max Super Specialty Hospital Saket, New Delhi, another coauthor on the panel. “The important thing is that at least some dose of all the four drugs needs to be introduced in the first 4-6 weeks, and then up-titrated.”

Other medical therapy can be more tailored, Dr. Metra noted, such as loop diuretics for patients with congestion, iron for those with iron deficiency, and other drugs depending on whether there is, for example, atrial fibrillation or coronary disease.
 

Adoption of emerging definitions

The document adopts the emerging characterization of HFrEF by a left ventricular ejection fraction (LVEF) up to 40%.

And it will leverage an expanding evidence base for medication in a segment of patients once said to have HF with preserved ejection fraction (HFpEF), who had therefore lacked specific, guideline-directed medical therapies. Now, patients with an LVEF of 41%-49% will be said to have HF with mildly reduced ejection fraction (HFmrEF), a tweak to the recently introduced HF with “mid-range” LVEF that is designed to assert its nature as something to treat. The new document’s HFmrEF recommendations come with various class and level-of-evidence ratings.

That leaves HFpEF to be characterized by an LVEF of 50% in combination with structural or functional abnormalities associated with LV diastolic dysfunction or raised LV filling pressures, including raised natriuretic peptide levels.

The definitions are consistent with those proposed internationally by the ESC-HFA, the Heart Failure Society of America, and other groups in a statement published in March.
 

Expanded HFrEF med landscape

Since the 2016 ESC guideline on HF therapy, Dr. McDonagh said, “there’s been no substantial change in the evidence for many of the classical drugs that we use in heart failure. However, we had a lot of new and exciting evidence to consider,” especially in support of the SGLT2 inhibitors as one of the core medications in HFrEF.

The new data came from two controlled trials in particular. In DAPA-HF, patients with HFrEF who were initially without diabetes and who went on dapagliflozin (Farxiga, AstraZeneca) showed a 27% drop in cardiovascular (CV) death or worsening-HF events over a median of 18 months.

“That was followed up with very concordant results with empagliflozin [Jardiance, Boehringer Ingelheim/Eli Lilly] in HFrEF in the EMPEROR-Reduced trial,” Dr. McDonagh said. In that trial, comparable patients who took empagliflozin showed a 25% drop in a primary endpoint similar to that in DAPA-HF over the median 16-month follow-up.

Other HFrEF recommendations are for selected patients. They include ivabradine, already in the guidelines, for patients in sinus rhythm with an elevated resting heart rate who can’t take beta-blockers for whatever reason. But, Dr. McDonagh noted, “we had some new classes of drugs to consider as well.”

In particular, the oral soluble guanylate-cyclase receptor stimulator vericiguat (Verquvo) emerged about a year ago from the VICTORIA trial as a modest success for patients with HFrEF and a previous HF hospitalization. In the trial with more than 5,000 patients, treatment with vericiguat atop standard drug and device therapy was followed by a significant 10% drop in risk for CV death or HF hospitalization.

Available now or likely to be available in the United States, the European Union, Japan, and other countries, vericiguat is recommended in the new guideline for VICTORIA-like patients who don’t adequately respond to other indicated medications.
 

Little for HFpEF as newly defined

“Almost nothing is new” in the guidelines for HFpEF, Dr. Metra said. The document recommends screening for and treatment of any underlying disorder and comorbidities, plus diuretics for any congestion. “That’s what we have to date.”

But that evidence base might soon change. The new HFpEF recommendations could possibly be up-staged at the ESC sessions by the August 27 scheduled presentation of EMPEROR-Preserved, a randomized test of empagliflozin in HFpEF and – it could be said – HFmrEF. The trial entered patients with chronic HF and an LVEF greater than 40%.

Eli Lilly and Boehringer Ingelheim offered the world a peek at the results, which suggest the SGLT2 inhibitor had a positive impact on the primary endpoint of CV death or HF hospitalization. They announced the cursory top-line outcomes in early July as part of its regulatory obligations, noting that the trial had “met” its primary endpoint.

But many unknowns remain, including the degree of benefit and whether it varied among subgroups, and especially whether outcomes were different for HFmrEF than for HFpEF.
 

Upgrades for familiar agents

Still, HFmrEF gets noteworthy attention in the document. “For the first time, we have recommendations for these patients,” Dr. Metra said. “We already knew that diuretics are indicated for the treatment of congestion. But now, ACE inhibitors, ARBs, beta-blockers, mineralocorticoid antagonists, as well as sacubitril/valsartan, may be considered to improve outcomes in these patients.” Their upgrades in the new guidelines were based on review of trials in the CHARM program and of TOPCAT and PARAGON-HF, among others, he said.

The new document also includes “treatment algorithms based on phenotypes”; that is, comorbidities and less common HF precipitants. For example, “assessment of iron status is now mandated in all patients with heart failure,” Dr. Metra said.

AFFIRM-HF is the key trial in this arena, with its more than 1,100 iron-deficient patients with LVEF less than 50% who had been recently hospitalized for HF. A year of treatment with ferric carboxymaltose (Ferinject/Injectafer, Vifor) led to a 26% drop in risk for HF hospitalization, but without affecting mortality.

For those who are iron deficient, Dr. Metra said, “ferric carboxymaltose intravenously should be considered not only in patients with low ejection fraction and outpatients, but also in patients recently hospitalized for acute heart failure.”

The SGLT2 inhibitors are recommended in HFrEF patients with type 2 diabetes. And treatment with tafamidis (Vyndaqel, Pfizer) in patients with genetic or wild-type transthyretin cardiac amyloidosis gets a class I recommendation based on survival gains seen in the ATTR-ACT trial.

Also recommended is a full CV assessment for patients with cancer who are on cardiotoxic agents or otherwise might be at risk for chemotherapy cardiotoxicity. “Beta-blockers and ACE inhibitors should be considered in those who develop left ventricular systolic dysfunction after anticancer therapy,” Dr. Metra said.

The ongoing pandemic made its mark on the document’s genesis, as it has with most everything else. “For better or worse, we were a ‘COVID guideline,’ ” Dr. McDonagh said. The writing committee consisted of “a large task force of 31 individuals, including two patients,” and there were “only two face-to-face meetings prior to the first wave of COVID hitting Europe.”

The committee voted on each of the recommendations, “and we had to have agreement of more than 75% of the task force to assign a class of recommendation or level of evidence,” she said. “I think we did the best we could in the circumstances. We had the benefit of many discussions over Zoom, and I think at the end of the day we have achieved a consensus.”

With such a large body of participants and the 75% threshold for agreement, “you end up with perhaps a conservative guideline. But that’s not a bad thing for clinical practice, for guidelines to be conservative,” Dr. McDonagh said. “They’re mainly concerned with looking at evidence and safety.”

A version of this article first appeared on Medscape.com.

Today there are so many evidence-based drug therapies for heart failure with reduced ejection fraction (HFrEF) that physicians treating HF patients almost don’t know what to do them.

It’s an exciting new age that way, but to many vexingly unclear how best to merge the shiny new options with mainstay regimens based on time-honored renin-angiotensin system (RAS) inhibitors and beta-blockers.

To impart some clarity, the authors of a new HF guideline document recently took center stage at the Heart Failure Association of the European Society of Cardiology (ESC-HFA) annual meeting to preview their updated recommendations, with novel twists based on recent major trials, for the new age of HF pharmacotherapeutics.

The guideline committee considered the evidence base that existed “up until the end of March of this year,” Theresa A. McDonagh, MD, King’s College London, said during the presentation. The document “is now finalized, it’s with the publishers, and it will be presented in full with simultaneous publication at the ESC meeting” that starts August 27.

It describes a game plan, already followed by some clinicians in practice without official guidance, for initiating drugs from each of four classes in virtually all patients with HFrEF.
 

New indicated drugs, new perspective for HFrEF

Three of the drug categories are old acquaintances. Among them are the RAS inhibitors, which include angiotensin-receptor/neprilysin inhibitors, beta-blockers, and the mineralocorticoid receptor antagonists. The latter drugs are gaining new respect after having been underplayed in HF prescribing despite longstanding evidence of efficacy.

Completing the quartet of first-line HFrEF drug classes is a recent arrival to the HF arena, the sodium-glucose cotransporter 2 inhibitors.

“We now have new data and a simplified treatment algorithm for heart failure with reduced ejection fraction based on the early administration of the four major classes of drugs,” said Marco Metra, MD, University of Brescia (Italy), previewing the medical-therapy portions of the new guideline at the ESC-HFA sessions, which launched virtually and live in Florence, Italy, on July 29.

The new game plan offers a simple answer to a once-common but complex question: How and in what order are the different drug classes initiated in patients with HFrEF? In the new document, the stated goal is to get them all on board expeditiously and safely, by any means possible.

The guideline writers did not specify a sequence, preferring to leave that decision to physicians, said Dr. Metra, who stated only two guiding principles. The first is to consider the patient’s unique circumstances. The order in which the drugs are introduced might vary, depending on, for example, whether the patient has low or high blood pressure or renal dysfunction.

Second, “it is very important that we try to give all four classes of drugs to the patient in the shortest time possible, because this saves lives,” he said.

That there is no recommendation on sequencing the drugs has led some to the wrong interpretation that all should be started at once, observed coauthor Javed Butler, MD, MPH, University of Mississippi, Jackson, as a panelist during the presentation. Far from it, he said. “The doctor with the patient in front of you can make the best decision. The idea here is to get all the therapies on as soon as possible, as safely as possible.”

“The order in which they are introduced is not really important,” agreed Vijay Chopra, MD, Max Super Specialty Hospital Saket, New Delhi, another coauthor on the panel. “The important thing is that at least some dose of all the four drugs needs to be introduced in the first 4-6 weeks, and then up-titrated.”

Other medical therapy can be more tailored, Dr. Metra noted, such as loop diuretics for patients with congestion, iron for those with iron deficiency, and other drugs depending on whether there is, for example, atrial fibrillation or coronary disease.
 

Adoption of emerging definitions

The document adopts the emerging characterization of HFrEF by a left ventricular ejection fraction (LVEF) up to 40%.

And it will leverage an expanding evidence base for medication in a segment of patients once said to have HF with preserved ejection fraction (HFpEF), who had therefore lacked specific, guideline-directed medical therapies. Now, patients with an LVEF of 41%-49% will be said to have HF with mildly reduced ejection fraction (HFmrEF), a tweak to the recently introduced HF with “mid-range” LVEF that is designed to assert its nature as something to treat. The new document’s HFmrEF recommendations come with various class and level-of-evidence ratings.

That leaves HFpEF to be characterized by an LVEF of 50% in combination with structural or functional abnormalities associated with LV diastolic dysfunction or raised LV filling pressures, including raised natriuretic peptide levels.

The definitions are consistent with those proposed internationally by the ESC-HFA, the Heart Failure Society of America, and other groups in a statement published in March.
 

Expanded HFrEF med landscape

Since the 2016 ESC guideline on HF therapy, Dr. McDonagh said, “there’s been no substantial change in the evidence for many of the classical drugs that we use in heart failure. However, we had a lot of new and exciting evidence to consider,” especially in support of the SGLT2 inhibitors as one of the core medications in HFrEF.

The new data came from two controlled trials in particular. In DAPA-HF, patients with HFrEF who were initially without diabetes and who went on dapagliflozin (Farxiga, AstraZeneca) showed a 27% drop in cardiovascular (CV) death or worsening-HF events over a median of 18 months.

“That was followed up with very concordant results with empagliflozin [Jardiance, Boehringer Ingelheim/Eli Lilly] in HFrEF in the EMPEROR-Reduced trial,” Dr. McDonagh said. In that trial, comparable patients who took empagliflozin showed a 25% drop in a primary endpoint similar to that in DAPA-HF over the median 16-month follow-up.

Other HFrEF recommendations are for selected patients. They include ivabradine, already in the guidelines, for patients in sinus rhythm with an elevated resting heart rate who can’t take beta-blockers for whatever reason. But, Dr. McDonagh noted, “we had some new classes of drugs to consider as well.”

In particular, the oral soluble guanylate-cyclase receptor stimulator vericiguat (Verquvo) emerged about a year ago from the VICTORIA trial as a modest success for patients with HFrEF and a previous HF hospitalization. In the trial with more than 5,000 patients, treatment with vericiguat atop standard drug and device therapy was followed by a significant 10% drop in risk for CV death or HF hospitalization.

Available now or likely to be available in the United States, the European Union, Japan, and other countries, vericiguat is recommended in the new guideline for VICTORIA-like patients who don’t adequately respond to other indicated medications.
 

Little for HFpEF as newly defined

“Almost nothing is new” in the guidelines for HFpEF, Dr. Metra said. The document recommends screening for and treatment of any underlying disorder and comorbidities, plus diuretics for any congestion. “That’s what we have to date.”

But that evidence base might soon change. The new HFpEF recommendations could possibly be up-staged at the ESC sessions by the August 27 scheduled presentation of EMPEROR-Preserved, a randomized test of empagliflozin in HFpEF and – it could be said – HFmrEF. The trial entered patients with chronic HF and an LVEF greater than 40%.

Eli Lilly and Boehringer Ingelheim offered the world a peek at the results, which suggest the SGLT2 inhibitor had a positive impact on the primary endpoint of CV death or HF hospitalization. They announced the cursory top-line outcomes in early July as part of its regulatory obligations, noting that the trial had “met” its primary endpoint.

But many unknowns remain, including the degree of benefit and whether it varied among subgroups, and especially whether outcomes were different for HFmrEF than for HFpEF.
 

Upgrades for familiar agents

Still, HFmrEF gets noteworthy attention in the document. “For the first time, we have recommendations for these patients,” Dr. Metra said. “We already knew that diuretics are indicated for the treatment of congestion. But now, ACE inhibitors, ARBs, beta-blockers, mineralocorticoid antagonists, as well as sacubitril/valsartan, may be considered to improve outcomes in these patients.” Their upgrades in the new guidelines were based on review of trials in the CHARM program and of TOPCAT and PARAGON-HF, among others, he said.

The new document also includes “treatment algorithms based on phenotypes”; that is, comorbidities and less common HF precipitants. For example, “assessment of iron status is now mandated in all patients with heart failure,” Dr. Metra said.

AFFIRM-HF is the key trial in this arena, with its more than 1,100 iron-deficient patients with LVEF less than 50% who had been recently hospitalized for HF. A year of treatment with ferric carboxymaltose (Ferinject/Injectafer, Vifor) led to a 26% drop in risk for HF hospitalization, but without affecting mortality.

For those who are iron deficient, Dr. Metra said, “ferric carboxymaltose intravenously should be considered not only in patients with low ejection fraction and outpatients, but also in patients recently hospitalized for acute heart failure.”

The SGLT2 inhibitors are recommended in HFrEF patients with type 2 diabetes. And treatment with tafamidis (Vyndaqel, Pfizer) in patients with genetic or wild-type transthyretin cardiac amyloidosis gets a class I recommendation based on survival gains seen in the ATTR-ACT trial.

Also recommended is a full CV assessment for patients with cancer who are on cardiotoxic agents or otherwise might be at risk for chemotherapy cardiotoxicity. “Beta-blockers and ACE inhibitors should be considered in those who develop left ventricular systolic dysfunction after anticancer therapy,” Dr. Metra said.

The ongoing pandemic made its mark on the document’s genesis, as it has with most everything else. “For better or worse, we were a ‘COVID guideline,’ ” Dr. McDonagh said. The writing committee consisted of “a large task force of 31 individuals, including two patients,” and there were “only two face-to-face meetings prior to the first wave of COVID hitting Europe.”

The committee voted on each of the recommendations, “and we had to have agreement of more than 75% of the task force to assign a class of recommendation or level of evidence,” she said. “I think we did the best we could in the circumstances. We had the benefit of many discussions over Zoom, and I think at the end of the day we have achieved a consensus.”

With such a large body of participants and the 75% threshold for agreement, “you end up with perhaps a conservative guideline. But that’s not a bad thing for clinical practice, for guidelines to be conservative,” Dr. McDonagh said. “They’re mainly concerned with looking at evidence and safety.”

A version of this article first appeared on Medscape.com.

Today there are so many evidence-based drug therapies for heart failure with reduced ejection fraction (HFrEF) that physicians treating HF patients almost don’t know what to do them.

It’s an exciting new age that way, but to many vexingly unclear how best to merge the shiny new options with mainstay regimens based on time-honored renin-angiotensin system (RAS) inhibitors and beta-blockers.

To impart some clarity, the authors of a new HF guideline document recently took center stage at the Heart Failure Association of the European Society of Cardiology (ESC-HFA) annual meeting to preview their updated recommendations, with novel twists based on recent major trials, for the new age of HF pharmacotherapeutics.

The guideline committee considered the evidence base that existed “up until the end of March of this year,” Theresa A. McDonagh, MD, King’s College London, said during the presentation. The document “is now finalized, it’s with the publishers, and it will be presented in full with simultaneous publication at the ESC meeting” that starts August 27.

It describes a game plan, already followed by some clinicians in practice without official guidance, for initiating drugs from each of four classes in virtually all patients with HFrEF.
 

New indicated drugs, new perspective for HFrEF

Three of the drug categories are old acquaintances. Among them are the RAS inhibitors, which include angiotensin-receptor/neprilysin inhibitors, beta-blockers, and the mineralocorticoid receptor antagonists. The latter drugs are gaining new respect after having been underplayed in HF prescribing despite longstanding evidence of efficacy.

Completing the quartet of first-line HFrEF drug classes is a recent arrival to the HF arena, the sodium-glucose cotransporter 2 inhibitors.

“We now have new data and a simplified treatment algorithm for heart failure with reduced ejection fraction based on the early administration of the four major classes of drugs,” said Marco Metra, MD, University of Brescia (Italy), previewing the medical-therapy portions of the new guideline at the ESC-HFA sessions, which launched virtually and live in Florence, Italy, on July 29.

The new game plan offers a simple answer to a once-common but complex question: How and in what order are the different drug classes initiated in patients with HFrEF? In the new document, the stated goal is to get them all on board expeditiously and safely, by any means possible.

The guideline writers did not specify a sequence, preferring to leave that decision to physicians, said Dr. Metra, who stated only two guiding principles. The first is to consider the patient’s unique circumstances. The order in which the drugs are introduced might vary, depending on, for example, whether the patient has low or high blood pressure or renal dysfunction.

Second, “it is very important that we try to give all four classes of drugs to the patient in the shortest time possible, because this saves lives,” he said.

That there is no recommendation on sequencing the drugs has led some to the wrong interpretation that all should be started at once, observed coauthor Javed Butler, MD, MPH, University of Mississippi, Jackson, as a panelist during the presentation. Far from it, he said. “The doctor with the patient in front of you can make the best decision. The idea here is to get all the therapies on as soon as possible, as safely as possible.”

“The order in which they are introduced is not really important,” agreed Vijay Chopra, MD, Max Super Specialty Hospital Saket, New Delhi, another coauthor on the panel. “The important thing is that at least some dose of all the four drugs needs to be introduced in the first 4-6 weeks, and then up-titrated.”

Other medical therapy can be more tailored, Dr. Metra noted, such as loop diuretics for patients with congestion, iron for those with iron deficiency, and other drugs depending on whether there is, for example, atrial fibrillation or coronary disease.
 

Adoption of emerging definitions

The document adopts the emerging characterization of HFrEF by a left ventricular ejection fraction (LVEF) up to 40%.

And it will leverage an expanding evidence base for medication in a segment of patients once said to have HF with preserved ejection fraction (HFpEF), who had therefore lacked specific, guideline-directed medical therapies. Now, patients with an LVEF of 41%-49% will be said to have HF with mildly reduced ejection fraction (HFmrEF), a tweak to the recently introduced HF with “mid-range” LVEF that is designed to assert its nature as something to treat. The new document’s HFmrEF recommendations come with various class and level-of-evidence ratings.

That leaves HFpEF to be characterized by an LVEF of 50% in combination with structural or functional abnormalities associated with LV diastolic dysfunction or raised LV filling pressures, including raised natriuretic peptide levels.

The definitions are consistent with those proposed internationally by the ESC-HFA, the Heart Failure Society of America, and other groups in a statement published in March.
 

Expanded HFrEF med landscape

Since the 2016 ESC guideline on HF therapy, Dr. McDonagh said, “there’s been no substantial change in the evidence for many of the classical drugs that we use in heart failure. However, we had a lot of new and exciting evidence to consider,” especially in support of the SGLT2 inhibitors as one of the core medications in HFrEF.

The new data came from two controlled trials in particular. In DAPA-HF, patients with HFrEF who were initially without diabetes and who went on dapagliflozin (Farxiga, AstraZeneca) showed a 27% drop in cardiovascular (CV) death or worsening-HF events over a median of 18 months.

“That was followed up with very concordant results with empagliflozin [Jardiance, Boehringer Ingelheim/Eli Lilly] in HFrEF in the EMPEROR-Reduced trial,” Dr. McDonagh said. In that trial, comparable patients who took empagliflozin showed a 25% drop in a primary endpoint similar to that in DAPA-HF over the median 16-month follow-up.

Other HFrEF recommendations are for selected patients. They include ivabradine, already in the guidelines, for patients in sinus rhythm with an elevated resting heart rate who can’t take beta-blockers for whatever reason. But, Dr. McDonagh noted, “we had some new classes of drugs to consider as well.”

In particular, the oral soluble guanylate-cyclase receptor stimulator vericiguat (Verquvo) emerged about a year ago from the VICTORIA trial as a modest success for patients with HFrEF and a previous HF hospitalization. In the trial with more than 5,000 patients, treatment with vericiguat atop standard drug and device therapy was followed by a significant 10% drop in risk for CV death or HF hospitalization.

Available now or likely to be available in the United States, the European Union, Japan, and other countries, vericiguat is recommended in the new guideline for VICTORIA-like patients who don’t adequately respond to other indicated medications.
 

Little for HFpEF as newly defined

“Almost nothing is new” in the guidelines for HFpEF, Dr. Metra said. The document recommends screening for and treatment of any underlying disorder and comorbidities, plus diuretics for any congestion. “That’s what we have to date.”

But that evidence base might soon change. The new HFpEF recommendations could possibly be up-staged at the ESC sessions by the August 27 scheduled presentation of EMPEROR-Preserved, a randomized test of empagliflozin in HFpEF and – it could be said – HFmrEF. The trial entered patients with chronic HF and an LVEF greater than 40%.

Eli Lilly and Boehringer Ingelheim offered the world a peek at the results, which suggest the SGLT2 inhibitor had a positive impact on the primary endpoint of CV death or HF hospitalization. They announced the cursory top-line outcomes in early July as part of its regulatory obligations, noting that the trial had “met” its primary endpoint.

But many unknowns remain, including the degree of benefit and whether it varied among subgroups, and especially whether outcomes were different for HFmrEF than for HFpEF.
 

Upgrades for familiar agents

Still, HFmrEF gets noteworthy attention in the document. “For the first time, we have recommendations for these patients,” Dr. Metra said. “We already knew that diuretics are indicated for the treatment of congestion. But now, ACE inhibitors, ARBs, beta-blockers, mineralocorticoid antagonists, as well as sacubitril/valsartan, may be considered to improve outcomes in these patients.” Their upgrades in the new guidelines were based on review of trials in the CHARM program and of TOPCAT and PARAGON-HF, among others, he said.

The new document also includes “treatment algorithms based on phenotypes”; that is, comorbidities and less common HF precipitants. For example, “assessment of iron status is now mandated in all patients with heart failure,” Dr. Metra said.

AFFIRM-HF is the key trial in this arena, with its more than 1,100 iron-deficient patients with LVEF less than 50% who had been recently hospitalized for HF. A year of treatment with ferric carboxymaltose (Ferinject/Injectafer, Vifor) led to a 26% drop in risk for HF hospitalization, but without affecting mortality.

For those who are iron deficient, Dr. Metra said, “ferric carboxymaltose intravenously should be considered not only in patients with low ejection fraction and outpatients, but also in patients recently hospitalized for acute heart failure.”

The SGLT2 inhibitors are recommended in HFrEF patients with type 2 diabetes. And treatment with tafamidis (Vyndaqel, Pfizer) in patients with genetic or wild-type transthyretin cardiac amyloidosis gets a class I recommendation based on survival gains seen in the ATTR-ACT trial.

Also recommended is a full CV assessment for patients with cancer who are on cardiotoxic agents or otherwise might be at risk for chemotherapy cardiotoxicity. “Beta-blockers and ACE inhibitors should be considered in those who develop left ventricular systolic dysfunction after anticancer therapy,” Dr. Metra said.

The ongoing pandemic made its mark on the document’s genesis, as it has with most everything else. “For better or worse, we were a ‘COVID guideline,’ ” Dr. McDonagh said. The writing committee consisted of “a large task force of 31 individuals, including two patients,” and there were “only two face-to-face meetings prior to the first wave of COVID hitting Europe.”

The committee voted on each of the recommendations, “and we had to have agreement of more than 75% of the task force to assign a class of recommendation or level of evidence,” she said. “I think we did the best we could in the circumstances. We had the benefit of many discussions over Zoom, and I think at the end of the day we have achieved a consensus.”

With such a large body of participants and the 75% threshold for agreement, “you end up with perhaps a conservative guideline. But that’s not a bad thing for clinical practice, for guidelines to be conservative,” Dr. McDonagh said. “They’re mainly concerned with looking at evidence and safety.”

A version of this article first appeared on Medscape.com.

A new decision pathway for the management of hypertriglyceridemia, prompted by a large and growing body of evidence that elevated triglycerides to a targetable risk factor for atherosclerotic cardiovascular disease (ASCVD), has been issued by the American College of Cardiology.

According to the chairman of the writing committee, Salim S. Virani, MD, PhD, the recommendations amplify and update more than alter the hypertriglyceridemia treatment recommendations in the 2018 joint multisociety blood cholesterol guidelines issued in 2018.

This decision pathway, however, is focused on triglycerides alone.

“The previous guidelines included a section on strategies for addressing hypertriglyceridemia to reduce ASCVD risk, but this new decision pathway builds on the recommendations with more details and with additional information,” explained Dr. Virani, professor of medicine in the section of cardiovascular research, Baylor College of Medicine, Houston.

Within this newly published document, the definitions of hypertriglyceridemia and rationale for treatment are followed by detailed algorithms for four specific patient groups with varying triglyceride levels:

• Adults with ASCVD.
• Adults at least 40 years of age with diabetes but no ASCVD.
• Adults at least 20 years of age with no ASCVD or diabetes.
• Adults at least 20 years of age with severe hypertriglyceridemia.

“In the design of these algorithms, we made an active effort to make them suitable for use by primary care physicians as well as specialists,” said Dr. Virani. Despite “lots of boxes and arrows,” the flowcharts for each of these patient groups permit clinicians to follow the decision pathway without having to reread the text.

The common emphasis in all four algorithms is to begin by evaluating patients for secondary causes of hypertriglyceridemia, such as multifactorial chylomicronemia syndrome and other diseases associated with elevated triglycerides. The next steps, also common to all algorithms, are to optimize diet and lifestyle changes that lower triglycerides, optimize glycemic control, and optimize statin therapy.

“Although commonly recognized for their impact on LDL-C, statins also provide a 10%-30% dose-dependent reduction in triglycerides in patients with elevated levels,” the guidelines state. Statins are considered a fundamental step to secondary prevention of ASCVD regardless of triglyceride levels.

Once treatable causes or contributors to hypertriglyceridemia have been addressed, lifestyle interventions and statin therapy have been optimized, pharmacologic therapy directed specifically at control of hypertriglyceridemia “can be considered” in those at highest risk of ASCVD events, but Dr. Virani explained that this is never an early or first step in control of elevated triglycerides.

“The entire working group agreed that lifestyle interventions should be highlighted front and center before considering any other intervention,” Dr. Virani explained.

Pharmacologic therapy for hypertriglyceridemia is not ignored. Prescription omega-3 fatty acid products are preferred over nonprescription dietary supplements, which may vary in quality and purity. But these products, rather than a standalone solution, are best applied within the context of efforts to improve diet, lower body weight, and increase physical activity.

Several trials have associated ethyl ester and carboxylic acid preparations with meaningful reductions in triglycerides, but these drugs, including icosapent ethyl (IPE), are not without adverse events. In the pivotal REDUCE-IT trial, IPE was linked with an increased risk of atrial fibrillation relative to placebo.

IPE is “the best option” and the only therapy with an indication for reduction in ASCVD risk, according to Dr. Virani, but he explained that safety concerns led the authors of the new decision pathway to employ cautious language in regard to its use, suggesting that it be “considered” in high-risk patients after other methods of lowering triglycerides have been optimized.

In the algorithm for the four different risk groups, the decision pathways follow stratifications for different levels of hypertriglyceridemia (defined under fasting and nonfasting conditions) and also for specific levels of LDL cholesterol. ASCVD risk assessment is also a factor in determining the next steps along the decision pathway.

According to Michael Davidson, MD, director of the lipid clinic at the University of Chicago, the emphasis on lifestyle changes for hypertriglyceridemia and the prudent language in regard to pharmacologic therapy is appropriate.

“In light of the controversies regarding the REDUCE-IT trial, the writing committee has done a nice job with providing useful guidance regarding the utilization of icosapent ethyl in higher risk patients,” Dr. Davidson said.

Calling the ACC decision pathway “a welcome enhancement of the 2018 ACC/AHA cholesterol guidelines,” Dr. Davidson praised the way in which the limitations of the evidence regarding pharmacologic therapies were explained.

“Most importantly, this decision pathway helps clinicians appreciate that hypertriglyceridemia can be best managed with lifestyle changes and addressing potential secondary causes,” Dr. Davidson said.

Dr. Virani reports no potential conflicts of interest. Dr. Davidson reports financial relationships with multiple pharmaceutical companies including those making or pursuing therapies for control of hypertriglyceridemia.

A new decision pathway for the management of hypertriglyceridemia, prompted by a large and growing body of evidence that elevated triglycerides to a targetable risk factor for atherosclerotic cardiovascular disease (ASCVD), has been issued by the American College of Cardiology.

According to the chairman of the writing committee, Salim S. Virani, MD, PhD, the recommendations amplify and update more than alter the hypertriglyceridemia treatment recommendations in the 2018 joint multisociety blood cholesterol guidelines issued in 2018.

This decision pathway, however, is focused on triglycerides alone.

“The previous guidelines included a section on strategies for addressing hypertriglyceridemia to reduce ASCVD risk, but this new decision pathway builds on the recommendations with more details and with additional information,” explained Dr. Virani, professor of medicine in the section of cardiovascular research, Baylor College of Medicine, Houston.

Within this newly published document, the definitions of hypertriglyceridemia and rationale for treatment are followed by detailed algorithms for four specific patient groups with varying triglyceride levels:

• Adults with ASCVD.
• Adults at least 40 years of age with diabetes but no ASCVD.
• Adults at least 20 years of age with no ASCVD or diabetes.
• Adults at least 20 years of age with severe hypertriglyceridemia.

“In the design of these algorithms, we made an active effort to make them suitable for use by primary care physicians as well as specialists,” said Dr. Virani. Despite “lots of boxes and arrows,” the flowcharts for each of these patient groups permit clinicians to follow the decision pathway without having to reread the text.

The common emphasis in all four algorithms is to begin by evaluating patients for secondary causes of hypertriglyceridemia, such as multifactorial chylomicronemia syndrome and other diseases associated with elevated triglycerides. The next steps, also common to all algorithms, are to optimize diet and lifestyle changes that lower triglycerides, optimize glycemic control, and optimize statin therapy.

“Although commonly recognized for their impact on LDL-C, statins also provide a 10%-30% dose-dependent reduction in triglycerides in patients with elevated levels,” the guidelines state. Statins are considered a fundamental step to secondary prevention of ASCVD regardless of triglyceride levels.

Once treatable causes or contributors to hypertriglyceridemia have been addressed, lifestyle interventions and statin therapy have been optimized, pharmacologic therapy directed specifically at control of hypertriglyceridemia “can be considered” in those at highest risk of ASCVD events, but Dr. Virani explained that this is never an early or first step in control of elevated triglycerides.

“The entire working group agreed that lifestyle interventions should be highlighted front and center before considering any other intervention,” Dr. Virani explained.

Pharmacologic therapy for hypertriglyceridemia is not ignored. Prescription omega-3 fatty acid products are preferred over nonprescription dietary supplements, which may vary in quality and purity. But these products, rather than a standalone solution, are best applied within the context of efforts to improve diet, lower body weight, and increase physical activity.

Several trials have associated ethyl ester and carboxylic acid preparations with meaningful reductions in triglycerides, but these drugs, including icosapent ethyl (IPE), are not without adverse events. In the pivotal REDUCE-IT trial, IPE was linked with an increased risk of atrial fibrillation relative to placebo.

IPE is “the best option” and the only therapy with an indication for reduction in ASCVD risk, according to Dr. Virani, but he explained that safety concerns led the authors of the new decision pathway to employ cautious language in regard to its use, suggesting that it be “considered” in high-risk patients after other methods of lowering triglycerides have been optimized.

In the algorithm for the four different risk groups, the decision pathways follow stratifications for different levels of hypertriglyceridemia (defined under fasting and nonfasting conditions) and also for specific levels of LDL cholesterol. ASCVD risk assessment is also a factor in determining the next steps along the decision pathway.

According to Michael Davidson, MD, director of the lipid clinic at the University of Chicago, the emphasis on lifestyle changes for hypertriglyceridemia and the prudent language in regard to pharmacologic therapy is appropriate.

“In light of the controversies regarding the REDUCE-IT trial, the writing committee has done a nice job with providing useful guidance regarding the utilization of icosapent ethyl in higher risk patients,” Dr. Davidson said.

Calling the ACC decision pathway “a welcome enhancement of the 2018 ACC/AHA cholesterol guidelines,” Dr. Davidson praised the way in which the limitations of the evidence regarding pharmacologic therapies were explained.

“Most importantly, this decision pathway helps clinicians appreciate that hypertriglyceridemia can be best managed with lifestyle changes and addressing potential secondary causes,” Dr. Davidson said.

Dr. Virani reports no potential conflicts of interest. Dr. Davidson reports financial relationships with multiple pharmaceutical companies including those making or pursuing therapies for control of hypertriglyceridemia.

A new decision pathway for the management of hypertriglyceridemia, prompted by a large and growing body of evidence that elevated triglycerides to a targetable risk factor for atherosclerotic cardiovascular disease (ASCVD), has been issued by the American College of Cardiology.

According to the chairman of the writing committee, Salim S. Virani, MD, PhD, the recommendations amplify and update more than alter the hypertriglyceridemia treatment recommendations in the 2018 joint multisociety blood cholesterol guidelines issued in 2018.

This decision pathway, however, is focused on triglycerides alone.

“The previous guidelines included a section on strategies for addressing hypertriglyceridemia to reduce ASCVD risk, but this new decision pathway builds on the recommendations with more details and with additional information,” explained Dr. Virani, professor of medicine in the section of cardiovascular research, Baylor College of Medicine, Houston.

Within this newly published document, the definitions of hypertriglyceridemia and rationale for treatment are followed by detailed algorithms for four specific patient groups with varying triglyceride levels:

• Adults with ASCVD.
• Adults at least 40 years of age with diabetes but no ASCVD.
• Adults at least 20 years of age with no ASCVD or diabetes.
• Adults at least 20 years of age with severe hypertriglyceridemia.

“In the design of these algorithms, we made an active effort to make them suitable for use by primary care physicians as well as specialists,” said Dr. Virani. Despite “lots of boxes and arrows,” the flowcharts for each of these patient groups permit clinicians to follow the decision pathway without having to reread the text.

The common emphasis in all four algorithms is to begin by evaluating patients for secondary causes of hypertriglyceridemia, such as multifactorial chylomicronemia syndrome and other diseases associated with elevated triglycerides. The next steps, also common to all algorithms, are to optimize diet and lifestyle changes that lower triglycerides, optimize glycemic control, and optimize statin therapy.

“Although commonly recognized for their impact on LDL-C, statins also provide a 10%-30% dose-dependent reduction in triglycerides in patients with elevated levels,” the guidelines state. Statins are considered a fundamental step to secondary prevention of ASCVD regardless of triglyceride levels.

Once treatable causes or contributors to hypertriglyceridemia have been addressed, lifestyle interventions and statin therapy have been optimized, pharmacologic therapy directed specifically at control of hypertriglyceridemia “can be considered” in those at highest risk of ASCVD events, but Dr. Virani explained that this is never an early or first step in control of elevated triglycerides.

“The entire working group agreed that lifestyle interventions should be highlighted front and center before considering any other intervention,” Dr. Virani explained.

Pharmacologic therapy for hypertriglyceridemia is not ignored. Prescription omega-3 fatty acid products are preferred over nonprescription dietary supplements, which may vary in quality and purity. But these products, rather than a standalone solution, are best applied within the context of efforts to improve diet, lower body weight, and increase physical activity.

Several trials have associated ethyl ester and carboxylic acid preparations with meaningful reductions in triglycerides, but these drugs, including icosapent ethyl (IPE), are not without adverse events. In the pivotal REDUCE-IT trial, IPE was linked with an increased risk of atrial fibrillation relative to placebo.

IPE is “the best option” and the only therapy with an indication for reduction in ASCVD risk, according to Dr. Virani, but he explained that safety concerns led the authors of the new decision pathway to employ cautious language in regard to its use, suggesting that it be “considered” in high-risk patients after other methods of lowering triglycerides have been optimized.

In the algorithm for the four different risk groups, the decision pathways follow stratifications for different levels of hypertriglyceridemia (defined under fasting and nonfasting conditions) and also for specific levels of LDL cholesterol. ASCVD risk assessment is also a factor in determining the next steps along the decision pathway.

According to Michael Davidson, MD, director of the lipid clinic at the University of Chicago, the emphasis on lifestyle changes for hypertriglyceridemia and the prudent language in regard to pharmacologic therapy is appropriate.

“In light of the controversies regarding the REDUCE-IT trial, the writing committee has done a nice job with providing useful guidance regarding the utilization of icosapent ethyl in higher risk patients,” Dr. Davidson said.

Calling the ACC decision pathway “a welcome enhancement of the 2018 ACC/AHA cholesterol guidelines,” Dr. Davidson praised the way in which the limitations of the evidence regarding pharmacologic therapies were explained.

“Most importantly, this decision pathway helps clinicians appreciate that hypertriglyceridemia can be best managed with lifestyle changes and addressing potential secondary causes,” Dr. Davidson said.

Dr. Virani reports no potential conflicts of interest. Dr. Davidson reports financial relationships with multiple pharmaceutical companies including those making or pursuing therapies for control of hypertriglyceridemia.

Sixteen years in the making, the American Academy of Pediatrics just released a new clinical practice guideline (CPG), “Evaluation and Management of Well-Appearing Febrile Infants 8-60 Days Old”. The recommendations were derived from interpretations of sequential studies in young, febrile, but well-appearing infants that covered invasive bacterial infection (IBI) incidence, diagnostic modalities, and treatment during the first 2 months of life, further refining approaches to evaluation and empirical treatment.
 

Pediatricians have long had solid information to help assess the risk for IBI among febrile infants aged 0-3 months, but there has been an ongoing desire to further refine the suggested evaluation of these very young infants. A study of febrile infants from the Pediatric Research in Office Settings network along with subsequent evidence has identified the first 3 weeks of life as the period of highest risk for IBI, with risk declining in a graded fashion aged between 22 and 56 days.
 

Critical caveats

First, some caveats. Infants 0-7 days are not addressed in the CPG, and all should be treated as high risk and receive full IBI evaluation according to newborn protocols. Second, the recommendations apply only to “well-appearing” infants. Any ill-appearing infant should be treated as high risk and receive full IBI evaluation and begun on empirical antimicrobials. Third, even though the CPG deals with infants as young as 8-21 days old, the recommendations are to treat all infants in this age group as high risk, even if well-appearing, and complete full IBI evaluation and empirical therapy while awaiting results. Fourth, these guidelines apply only to infants born at 37 weeks’ gestation or more. Finally, the new CPG action statements are meant to be recommendations rather than a standard of medical care, leaving some leeway for clinician interpretation of individual patient scenarios. Where appropriate, parents’ values and preferences should be incorporated as part of shared decision-making.

The CPG divides young, febrile infants into three cohorts based on age:

• 8-21 days old
• 22-28 days old
• 29-60 days old

Age 8-21 days

For well-appearing febrile infants 8-21 days old, the CPG recommends a complete IBI evaluation that includes urine, blood, and cerebrospinal fluid (CSF) for culture, approaching all infants in this cohort as high risk. Inflammatory markers may be obtained, but the evidence is not comprehensive enough to evaluate their role in decision-making for this age group. A two-step urine evaluation method (urine analysis followed by culture if the urine analysis looks concerning) is not recommended for infants aged 8-21 days. Urine samples for culture from these young infants should be obtained by catheterization or suprapubic aspiration.

The CPG recommends drawing blood cultures and CSF by lumbar puncture from this cohort. These infants should be admitted to the hospital, treated empirically with antimicrobials, and actively monitored. However, if the cultures are negative at 24-36 hours, the clinician should discontinue antimicrobials and discharge the infant if there is no other reason for continued hospitalization.
 

Age 22-28 days

Well-appearing, febrile infants 22-28 days old are in an intermediate-risk zone. The recommendation for infants in this cohort is to obtain a urine specimen by catheterization or suprapubic aspiration for both urine analysis and culture. Clinicians may consider obtaining urine samples for analysis noninvasively (e.g., urine bag) in this cohort, but this is not the preferred method.

Blood culture should be obtained from all infants in this group. Inflammatory markers can help clinicians identify infants at greater risk for IBI, including meningitis. Previous data suggested that inflammatory markers such as serum white blood cell counts greater than 11,000/mcL, a serum absolute neutrophil count of greater than 4,000/mcL, and elevated C-reactive protein and procalcitonin levels could help providers identify febrile infants with true IBI. A 2008 study demonstrated that procalcitonin had the best receiver operating characteristic curve in regard to predicting IBI in young febrile infants. Other research backed up that finding and identified cutoff values for procalcitonin levels greater than 1.0 ng/mL. The CPG recommends considering a procalcitonin value of 0.5 ng/mL or higher as positive, indicating that the infant is at greater risk for IBI and potentially should undergo an expanded IBI workup. Therefore, in infants aged 22-28 days, inflammatory markers can play a role in deciding whether to perform a lumbar puncture.

Many more nuanced recommendations for whether to and how to empirically treat with antimicrobials in this cohort can be found in the CPG, including whether to manage in the hospital or at home. Treatment recommendations vary greatly for this cohort on the basis of the tests obtained and whether tests were positive or negative at the initial evaluation.
 

Age 29-60 days

The CPG will be most helpful when clinicians are faced with well-appearing, febrile infants in the 29- to 60-day age group. As with the other groups, a urine evaluation is recommended; however, the CPG suggests that the two-step approach – obtaining a urine analysis by a noninvasive method and only obtaining culture if the urine analysis is positive – is reasonable. This means that a bag or free-flowing urine specimen would be appropriate for urinalysis, followed by catheterization/suprapubic aspiration if a culture is necessary. This would save approximately 90% of infants from invasive urine collection. Regardless, only catheter or suprapubic specimens are appropriate for urine culture.

The CPG also recommends that clinicians obtain blood culture on all of these infants. Inflammatory markers should be assessed in this cohort because avoiding lumbar puncture for CSF culture would be appropriate in this cohort if the inflammatory markers are negative. If CSF is obtained in this age cohort, enterovirus testing should be added to the testing regimen. Again, for any infant considered at higher risk for IBI on the basis of screening tests, the CPG recommends a 24- to 36-hour rule-out period with empirical antimicrobial treatment and active monitoring in the hospital.
 

Summary

The recommended approach for febrile infants 8-21 days old is relatively aggressive, with urine, blood, and CSF evaluation for IBI. Clinicians gain some leeway for infants age 22-28 days, but the guidelines recommend a more flexible approach to evaluating well-appearing, febrile infants age 29-60 days, when a two-step urine evaluation and inflammatory marker assessment can help clinicians and parents have a better discussion about the risk-benefit trade-offs of more aggressive testing and empirical treatment.

The author would like to thank Ken Roberts, MD, for his review and helpful comments on this summary of the CPG highlights. Summary points of the CPG were presented by the writing group at the 2021 Pediatric Academic Societies meeting.

William T. Basco, Jr, MD, MS, is a professor of pediatrics at the Medical University of South Carolina, Charleston, and director of the division of general pediatrics. He is an active health services researcher and has published more than 60 manuscripts in the peer-reviewed literature.

A version of this article first appeared on Medscape.com.

Sixteen years in the making, the American Academy of Pediatrics just released a new clinical practice guideline (CPG), “Evaluation and Management of Well-Appearing Febrile Infants 8-60 Days Old”. The recommendations were derived from interpretations of sequential studies in young, febrile, but well-appearing infants that covered invasive bacterial infection (IBI) incidence, diagnostic modalities, and treatment during the first 2 months of life, further refining approaches to evaluation and empirical treatment.
 

Pediatricians have long had solid information to help assess the risk for IBI among febrile infants aged 0-3 months, but there has been an ongoing desire to further refine the suggested evaluation of these very young infants. A study of febrile infants from the Pediatric Research in Office Settings network along with subsequent evidence has identified the first 3 weeks of life as the period of highest risk for IBI, with risk declining in a graded fashion aged between 22 and 56 days.
 

Critical caveats

First, some caveats. Infants 0-7 days are not addressed in the CPG, and all should be treated as high risk and receive full IBI evaluation according to newborn protocols. Second, the recommendations apply only to “well-appearing” infants. Any ill-appearing infant should be treated as high risk and receive full IBI evaluation and begun on empirical antimicrobials. Third, even though the CPG deals with infants as young as 8-21 days old, the recommendations are to treat all infants in this age group as high risk, even if well-appearing, and complete full IBI evaluation and empirical therapy while awaiting results. Fourth, these guidelines apply only to infants born at 37 weeks’ gestation or more. Finally, the new CPG action statements are meant to be recommendations rather than a standard of medical care, leaving some leeway for clinician interpretation of individual patient scenarios. Where appropriate, parents’ values and preferences should be incorporated as part of shared decision-making.

The CPG divides young, febrile infants into three cohorts based on age:

• 8-21 days old
• 22-28 days old
• 29-60 days old

Age 8-21 days

For well-appearing febrile infants 8-21 days old, the CPG recommends a complete IBI evaluation that includes urine, blood, and cerebrospinal fluid (CSF) for culture, approaching all infants in this cohort as high risk. Inflammatory markers may be obtained, but the evidence is not comprehensive enough to evaluate their role in decision-making for this age group. A two-step urine evaluation method (urine analysis followed by culture if the urine analysis looks concerning) is not recommended for infants aged 8-21 days. Urine samples for culture from these young infants should be obtained by catheterization or suprapubic aspiration.

The CPG recommends drawing blood cultures and CSF by lumbar puncture from this cohort. These infants should be admitted to the hospital, treated empirically with antimicrobials, and actively monitored. However, if the cultures are negative at 24-36 hours, the clinician should discontinue antimicrobials and discharge the infant if there is no other reason for continued hospitalization.
 

Age 22-28 days

Well-appearing, febrile infants 22-28 days old are in an intermediate-risk zone. The recommendation for infants in this cohort is to obtain a urine specimen by catheterization or suprapubic aspiration for both urine analysis and culture. Clinicians may consider obtaining urine samples for analysis noninvasively (e.g., urine bag) in this cohort, but this is not the preferred method.

Blood culture should be obtained from all infants in this group. Inflammatory markers can help clinicians identify infants at greater risk for IBI, including meningitis. Previous data suggested that inflammatory markers such as serum white blood cell counts greater than 11,000/mcL, a serum absolute neutrophil count of greater than 4,000/mcL, and elevated C-reactive protein and procalcitonin levels could help providers identify febrile infants with true IBI. A 2008 study demonstrated that procalcitonin had the best receiver operating characteristic curve in regard to predicting IBI in young febrile infants. Other research backed up that finding and identified cutoff values for procalcitonin levels greater than 1.0 ng/mL. The CPG recommends considering a procalcitonin value of 0.5 ng/mL or higher as positive, indicating that the infant is at greater risk for IBI and potentially should undergo an expanded IBI workup. Therefore, in infants aged 22-28 days, inflammatory markers can play a role in deciding whether to perform a lumbar puncture.

Many more nuanced recommendations for whether to and how to empirically treat with antimicrobials in this cohort can be found in the CPG, including whether to manage in the hospital or at home. Treatment recommendations vary greatly for this cohort on the basis of the tests obtained and whether tests were positive or negative at the initial evaluation.
 

Age 29-60 days

The CPG will be most helpful when clinicians are faced with well-appearing, febrile infants in the 29- to 60-day age group. As with the other groups, a urine evaluation is recommended; however, the CPG suggests that the two-step approach – obtaining a urine analysis by a noninvasive method and only obtaining culture if the urine analysis is positive – is reasonable. This means that a bag or free-flowing urine specimen would be appropriate for urinalysis, followed by catheterization/suprapubic aspiration if a culture is necessary. This would save approximately 90% of infants from invasive urine collection. Regardless, only catheter or suprapubic specimens are appropriate for urine culture.

The CPG also recommends that clinicians obtain blood culture on all of these infants. Inflammatory markers should be assessed in this cohort because avoiding lumbar puncture for CSF culture would be appropriate in this cohort if the inflammatory markers are negative. If CSF is obtained in this age cohort, enterovirus testing should be added to the testing regimen. Again, for any infant considered at higher risk for IBI on the basis of screening tests, the CPG recommends a 24- to 36-hour rule-out period with empirical antimicrobial treatment and active monitoring in the hospital.
 

Summary

The recommended approach for febrile infants 8-21 days old is relatively aggressive, with urine, blood, and CSF evaluation for IBI. Clinicians gain some leeway for infants age 22-28 days, but the guidelines recommend a more flexible approach to evaluating well-appearing, febrile infants age 29-60 days, when a two-step urine evaluation and inflammatory marker assessment can help clinicians and parents have a better discussion about the risk-benefit trade-offs of more aggressive testing and empirical treatment.

The author would like to thank Ken Roberts, MD, for his review and helpful comments on this summary of the CPG highlights. Summary points of the CPG were presented by the writing group at the 2021 Pediatric Academic Societies meeting.

William T. Basco, Jr, MD, MS, is a professor of pediatrics at the Medical University of South Carolina, Charleston, and director of the division of general pediatrics. He is an active health services researcher and has published more than 60 manuscripts in the peer-reviewed literature.

A version of this article first appeared on Medscape.com.

Sixteen years in the making, the American Academy of Pediatrics just released a new clinical practice guideline (CPG), “Evaluation and Management of Well-Appearing Febrile Infants 8-60 Days Old”. The recommendations were derived from interpretations of sequential studies in young, febrile, but well-appearing infants that covered invasive bacterial infection (IBI) incidence, diagnostic modalities, and treatment during the first 2 months of life, further refining approaches to evaluation and empirical treatment.
 

Pediatricians have long had solid information to help assess the risk for IBI among febrile infants aged 0-3 months, but there has been an ongoing desire to further refine the suggested evaluation of these very young infants. A study of febrile infants from the Pediatric Research in Office Settings network along with subsequent evidence has identified the first 3 weeks of life as the period of highest risk for IBI, with risk declining in a graded fashion aged between 22 and 56 days.
 

Critical caveats

First, some caveats. Infants 0-7 days are not addressed in the CPG, and all should be treated as high risk and receive full IBI evaluation according to newborn protocols. Second, the recommendations apply only to “well-appearing” infants. Any ill-appearing infant should be treated as high risk and receive full IBI evaluation and begun on empirical antimicrobials. Third, even though the CPG deals with infants as young as 8-21 days old, the recommendations are to treat all infants in this age group as high risk, even if well-appearing, and complete full IBI evaluation and empirical therapy while awaiting results. Fourth, these guidelines apply only to infants born at 37 weeks’ gestation or more. Finally, the new CPG action statements are meant to be recommendations rather than a standard of medical care, leaving some leeway for clinician interpretation of individual patient scenarios. Where appropriate, parents’ values and preferences should be incorporated as part of shared decision-making.

The CPG divides young, febrile infants into three cohorts based on age:

• 8-21 days old
• 22-28 days old
• 29-60 days old

Age 8-21 days

For well-appearing febrile infants 8-21 days old, the CPG recommends a complete IBI evaluation that includes urine, blood, and cerebrospinal fluid (CSF) for culture, approaching all infants in this cohort as high risk. Inflammatory markers may be obtained, but the evidence is not comprehensive enough to evaluate their role in decision-making for this age group. A two-step urine evaluation method (urine analysis followed by culture if the urine analysis looks concerning) is not recommended for infants aged 8-21 days. Urine samples for culture from these young infants should be obtained by catheterization or suprapubic aspiration.

The CPG recommends drawing blood cultures and CSF by lumbar puncture from this cohort. These infants should be admitted to the hospital, treated empirically with antimicrobials, and actively monitored. However, if the cultures are negative at 24-36 hours, the clinician should discontinue antimicrobials and discharge the infant if there is no other reason for continued hospitalization.
 

Age 22-28 days

Well-appearing, febrile infants 22-28 days old are in an intermediate-risk zone. The recommendation for infants in this cohort is to obtain a urine specimen by catheterization or suprapubic aspiration for both urine analysis and culture. Clinicians may consider obtaining urine samples for analysis noninvasively (e.g., urine bag) in this cohort, but this is not the preferred method.

Blood culture should be obtained from all infants in this group. Inflammatory markers can help clinicians identify infants at greater risk for IBI, including meningitis. Previous data suggested that inflammatory markers such as serum white blood cell counts greater than 11,000/mcL, a serum absolute neutrophil count of greater than 4,000/mcL, and elevated C-reactive protein and procalcitonin levels could help providers identify febrile infants with true IBI. A 2008 study demonstrated that procalcitonin had the best receiver operating characteristic curve in regard to predicting IBI in young febrile infants. Other research backed up that finding and identified cutoff values for procalcitonin levels greater than 1.0 ng/mL. The CPG recommends considering a procalcitonin value of 0.5 ng/mL or higher as positive, indicating that the infant is at greater risk for IBI and potentially should undergo an expanded IBI workup. Therefore, in infants aged 22-28 days, inflammatory markers can play a role in deciding whether to perform a lumbar puncture.

Many more nuanced recommendations for whether to and how to empirically treat with antimicrobials in this cohort can be found in the CPG, including whether to manage in the hospital or at home. Treatment recommendations vary greatly for this cohort on the basis of the tests obtained and whether tests were positive or negative at the initial evaluation.
 

Age 29-60 days

The CPG will be most helpful when clinicians are faced with well-appearing, febrile infants in the 29- to 60-day age group. As with the other groups, a urine evaluation is recommended; however, the CPG suggests that the two-step approach – obtaining a urine analysis by a noninvasive method and only obtaining culture if the urine analysis is positive – is reasonable. This means that a bag or free-flowing urine specimen would be appropriate for urinalysis, followed by catheterization/suprapubic aspiration if a culture is necessary. This would save approximately 90% of infants from invasive urine collection. Regardless, only catheter or suprapubic specimens are appropriate for urine culture.

The CPG also recommends that clinicians obtain blood culture on all of these infants. Inflammatory markers should be assessed in this cohort because avoiding lumbar puncture for CSF culture would be appropriate in this cohort if the inflammatory markers are negative. If CSF is obtained in this age cohort, enterovirus testing should be added to the testing regimen. Again, for any infant considered at higher risk for IBI on the basis of screening tests, the CPG recommends a 24- to 36-hour rule-out period with empirical antimicrobial treatment and active monitoring in the hospital.
 

Summary

The recommended approach for febrile infants 8-21 days old is relatively aggressive, with urine, blood, and CSF evaluation for IBI. Clinicians gain some leeway for infants age 22-28 days, but the guidelines recommend a more flexible approach to evaluating well-appearing, febrile infants age 29-60 days, when a two-step urine evaluation and inflammatory marker assessment can help clinicians and parents have a better discussion about the risk-benefit trade-offs of more aggressive testing and empirical treatment.

The author would like to thank Ken Roberts, MD, for his review and helpful comments on this summary of the CPG highlights. Summary points of the CPG were presented by the writing group at the 2021 Pediatric Academic Societies meeting.

William T. Basco, Jr, MD, MS, is a professor of pediatrics at the Medical University of South Carolina, Charleston, and director of the division of general pediatrics. He is an active health services researcher and has published more than 60 manuscripts in the peer-reviewed literature.

A version of this article first appeared on Medscape.com.