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ICMs detect serious arrhythmias in high-risk post-MI patients: SMART-MI
Prevention strategies may be next
After a myocardial infarction, implantable cardiac monitors (ICMs) are sensitive for detecting serious arrhythmias in patients with cardiac autonomic dysfunction but only moderately reduced left ventricular ejection fraction (LVEF), according to results of the randomized SMART-MI trial.
When remote monitoring with the ICM was compared with conventional follow-up in this group of patients, serious arrhythmic events were detected at a nearly sixfold greater rate, reported Axel Bauer, MD, at the annual congress of the European Society of Cardiology.
The study further showed that these events were closely associated with subsequent major adverse cardiac and cerebrovascular events (MACCE).
“SMART-MI is the first study to test an implantable device in high-risk MI patients with a LVEF greater than 35%,” reported Dr. Bauer, a cardiologist and director of the internal medicine clinic, University of Innsbruck (Austria). It showed that the types and frequency of arrhythmias were “comparable to those of post-MI patients with reduced LVEF.”
The ability to assess risk is potentially significant because “the majority of cardiovascular complications, including sudden death, occur in patients with only moderately reduced LVEF,” explained Dr. Bauer.
Despite the greater risk, “there are no preventive strategies so far” currently available for this group, he said.
The SMART-MI study confirms the need for treatments, confirms a method for monitoring risk, and might provide the basis for trials designed to test treatments to modify this risk, he added.
ECG used to define autonomic dysfunction
In the SMART MI protocol, 1,305 survivors of MI with LVEF of 36%-50% at 33 participating centers in Austria and Germany were evaluated with a 20-minute high resolution electrocardiogram. They were enrolled and randomized if they demonstrated cardiac autonomic dysfunction on at least two validated ECG biomarkers.
The 400 participants were randomized to implantation of a ICM, which transmitted daily reports to a ICM core laboratory, or to conventional follow-up.
After a median follow-up of 21 months, serious events were detected in 60 of the 201 patients in the ICM group and 12 of the 199 patients in the control group (29% vs. 6%). Serious adverse events were defined as those that would typically warrant therapy, such as prolonged atrial fibrillation (at least 6 minutes) high-degree atrioventricular block, and sustained ventricular tachycardia.
The difference in the detection rate, which was the primary endpoint, was highly significant (P < .0001), but the study was also able to confirm that these events predicted MACCE, a secondary study endpoint. In those with a serious arrhythmia, the hazard ratio for subsequent MACCE was approximately sevenfold greater relative to those without a serious arrhythmia. This was true of those in the ICM group (HR, 6.8; P < .001) and controls (HR 7.3; P < .001).
Arrhythmias warn of impending complications
“The data show that the prognostic impact of detecting a serious arrhythmia does not depend on the mode of detection,” Dr. Bauer reported. The data also confirm that “subclinical serious arrhythmia events are a warning signal for an impending complication.”
Although more interventions – including pacemakers, catheter ablations, and oral anticoagulants – were offered to patients in the experimental arm, “the study was not powered to show differences in outcomes,” and, in fact, no significant differences were observed, according to Dr. Bauer. However, the evidence that ICM is effective for detecting arrhythmias does provide a structure on which to build clinical trials.
“We now need the trials to see if ICM can change practice and improve outcomes,” said Carlos Aguiar, MD, a staff cardiologist at the Hospital Santa Cruz, Lisbon. He acknowledged that this study proves that ICM can detect serious arrhythmias in patients with moderate left ventricular dysfunction, but “we need to develop and test treatment paths.”
Dr. Aguiar considers SMART-MI an important study that “goes to the heart” of a common clinical dilemma.
“In clinical practice, we see patients with LVEF that is not that suppressed and so do not have a class I indication for ICM, but there are often features that might have you concerned and make you think it would be great if the LVEF was 35% or lower [to justify intervention],” Dr. Aguiar said.
Data provide insight on unaddressed risk group
SMART-MI confirms earlier evidence that post-MI patients with cardiac autonomic dysfunction are at high risk. Currently, this relative increase in risk goes “unaddressed,” according to Dr. Bauer. Although he contended that the risk itself “could be an indication for ICM in a high-risk patient group without classically defined left ventricular dysfunction,” he agreed that the ultimate value of this trial might be that it “opens a window” for a rationale to test preventive strategies.
An invited ESC discussant, Gerhard Hindricks, MD, PhD, praised the study for drawing attention to the risk of events in a subset of post-MI patients with LVEF of 35% or greater. However, he suggested that criteria other than those based on ECG might be more sensitive for selecting patients who might benefit from intervention.
“We do not know whether additional methods of establishing risk, such as imaging, might be valuable,” said Dr. Hindricks, chief of the department of arrhythmology in the Heart Institute of the University of Leipzig (Germany). He believes work in this area is needed to ensure appropriate entry criteria for interventional trials designed to modify risk in post-MI patients who do not meet the traditional definition of reduced ejection fraction.
Dr. Bauer reports financial relationships with Medtronic, which sponsored this study, as well as Bayer, Boehringer Ingelheim, Edwards, and Novartis. Dr. Aguiar reports no relevant financial conflicts.
Prevention strategies may be next
Prevention strategies may be next
After a myocardial infarction, implantable cardiac monitors (ICMs) are sensitive for detecting serious arrhythmias in patients with cardiac autonomic dysfunction but only moderately reduced left ventricular ejection fraction (LVEF), according to results of the randomized SMART-MI trial.
When remote monitoring with the ICM was compared with conventional follow-up in this group of patients, serious arrhythmic events were detected at a nearly sixfold greater rate, reported Axel Bauer, MD, at the annual congress of the European Society of Cardiology.
The study further showed that these events were closely associated with subsequent major adverse cardiac and cerebrovascular events (MACCE).
“SMART-MI is the first study to test an implantable device in high-risk MI patients with a LVEF greater than 35%,” reported Dr. Bauer, a cardiologist and director of the internal medicine clinic, University of Innsbruck (Austria). It showed that the types and frequency of arrhythmias were “comparable to those of post-MI patients with reduced LVEF.”
The ability to assess risk is potentially significant because “the majority of cardiovascular complications, including sudden death, occur in patients with only moderately reduced LVEF,” explained Dr. Bauer.
Despite the greater risk, “there are no preventive strategies so far” currently available for this group, he said.
The SMART-MI study confirms the need for treatments, confirms a method for monitoring risk, and might provide the basis for trials designed to test treatments to modify this risk, he added.
ECG used to define autonomic dysfunction
In the SMART MI protocol, 1,305 survivors of MI with LVEF of 36%-50% at 33 participating centers in Austria and Germany were evaluated with a 20-minute high resolution electrocardiogram. They were enrolled and randomized if they demonstrated cardiac autonomic dysfunction on at least two validated ECG biomarkers.
The 400 participants were randomized to implantation of a ICM, which transmitted daily reports to a ICM core laboratory, or to conventional follow-up.
After a median follow-up of 21 months, serious events were detected in 60 of the 201 patients in the ICM group and 12 of the 199 patients in the control group (29% vs. 6%). Serious adverse events were defined as those that would typically warrant therapy, such as prolonged atrial fibrillation (at least 6 minutes) high-degree atrioventricular block, and sustained ventricular tachycardia.
The difference in the detection rate, which was the primary endpoint, was highly significant (P < .0001), but the study was also able to confirm that these events predicted MACCE, a secondary study endpoint. In those with a serious arrhythmia, the hazard ratio for subsequent MACCE was approximately sevenfold greater relative to those without a serious arrhythmia. This was true of those in the ICM group (HR, 6.8; P < .001) and controls (HR 7.3; P < .001).
Arrhythmias warn of impending complications
“The data show that the prognostic impact of detecting a serious arrhythmia does not depend on the mode of detection,” Dr. Bauer reported. The data also confirm that “subclinical serious arrhythmia events are a warning signal for an impending complication.”
Although more interventions – including pacemakers, catheter ablations, and oral anticoagulants – were offered to patients in the experimental arm, “the study was not powered to show differences in outcomes,” and, in fact, no significant differences were observed, according to Dr. Bauer. However, the evidence that ICM is effective for detecting arrhythmias does provide a structure on which to build clinical trials.
“We now need the trials to see if ICM can change practice and improve outcomes,” said Carlos Aguiar, MD, a staff cardiologist at the Hospital Santa Cruz, Lisbon. He acknowledged that this study proves that ICM can detect serious arrhythmias in patients with moderate left ventricular dysfunction, but “we need to develop and test treatment paths.”
Dr. Aguiar considers SMART-MI an important study that “goes to the heart” of a common clinical dilemma.
“In clinical practice, we see patients with LVEF that is not that suppressed and so do not have a class I indication for ICM, but there are often features that might have you concerned and make you think it would be great if the LVEF was 35% or lower [to justify intervention],” Dr. Aguiar said.
Data provide insight on unaddressed risk group
SMART-MI confirms earlier evidence that post-MI patients with cardiac autonomic dysfunction are at high risk. Currently, this relative increase in risk goes “unaddressed,” according to Dr. Bauer. Although he contended that the risk itself “could be an indication for ICM in a high-risk patient group without classically defined left ventricular dysfunction,” he agreed that the ultimate value of this trial might be that it “opens a window” for a rationale to test preventive strategies.
An invited ESC discussant, Gerhard Hindricks, MD, PhD, praised the study for drawing attention to the risk of events in a subset of post-MI patients with LVEF of 35% or greater. However, he suggested that criteria other than those based on ECG might be more sensitive for selecting patients who might benefit from intervention.
“We do not know whether additional methods of establishing risk, such as imaging, might be valuable,” said Dr. Hindricks, chief of the department of arrhythmology in the Heart Institute of the University of Leipzig (Germany). He believes work in this area is needed to ensure appropriate entry criteria for interventional trials designed to modify risk in post-MI patients who do not meet the traditional definition of reduced ejection fraction.
Dr. Bauer reports financial relationships with Medtronic, which sponsored this study, as well as Bayer, Boehringer Ingelheim, Edwards, and Novartis. Dr. Aguiar reports no relevant financial conflicts.
After a myocardial infarction, implantable cardiac monitors (ICMs) are sensitive for detecting serious arrhythmias in patients with cardiac autonomic dysfunction but only moderately reduced left ventricular ejection fraction (LVEF), according to results of the randomized SMART-MI trial.
When remote monitoring with the ICM was compared with conventional follow-up in this group of patients, serious arrhythmic events were detected at a nearly sixfold greater rate, reported Axel Bauer, MD, at the annual congress of the European Society of Cardiology.
The study further showed that these events were closely associated with subsequent major adverse cardiac and cerebrovascular events (MACCE).
“SMART-MI is the first study to test an implantable device in high-risk MI patients with a LVEF greater than 35%,” reported Dr. Bauer, a cardiologist and director of the internal medicine clinic, University of Innsbruck (Austria). It showed that the types and frequency of arrhythmias were “comparable to those of post-MI patients with reduced LVEF.”
The ability to assess risk is potentially significant because “the majority of cardiovascular complications, including sudden death, occur in patients with only moderately reduced LVEF,” explained Dr. Bauer.
Despite the greater risk, “there are no preventive strategies so far” currently available for this group, he said.
The SMART-MI study confirms the need for treatments, confirms a method for monitoring risk, and might provide the basis for trials designed to test treatments to modify this risk, he added.
ECG used to define autonomic dysfunction
In the SMART MI protocol, 1,305 survivors of MI with LVEF of 36%-50% at 33 participating centers in Austria and Germany were evaluated with a 20-minute high resolution electrocardiogram. They were enrolled and randomized if they demonstrated cardiac autonomic dysfunction on at least two validated ECG biomarkers.
The 400 participants were randomized to implantation of a ICM, which transmitted daily reports to a ICM core laboratory, or to conventional follow-up.
After a median follow-up of 21 months, serious events were detected in 60 of the 201 patients in the ICM group and 12 of the 199 patients in the control group (29% vs. 6%). Serious adverse events were defined as those that would typically warrant therapy, such as prolonged atrial fibrillation (at least 6 minutes) high-degree atrioventricular block, and sustained ventricular tachycardia.
The difference in the detection rate, which was the primary endpoint, was highly significant (P < .0001), but the study was also able to confirm that these events predicted MACCE, a secondary study endpoint. In those with a serious arrhythmia, the hazard ratio for subsequent MACCE was approximately sevenfold greater relative to those without a serious arrhythmia. This was true of those in the ICM group (HR, 6.8; P < .001) and controls (HR 7.3; P < .001).
Arrhythmias warn of impending complications
“The data show that the prognostic impact of detecting a serious arrhythmia does not depend on the mode of detection,” Dr. Bauer reported. The data also confirm that “subclinical serious arrhythmia events are a warning signal for an impending complication.”
Although more interventions – including pacemakers, catheter ablations, and oral anticoagulants – were offered to patients in the experimental arm, “the study was not powered to show differences in outcomes,” and, in fact, no significant differences were observed, according to Dr. Bauer. However, the evidence that ICM is effective for detecting arrhythmias does provide a structure on which to build clinical trials.
“We now need the trials to see if ICM can change practice and improve outcomes,” said Carlos Aguiar, MD, a staff cardiologist at the Hospital Santa Cruz, Lisbon. He acknowledged that this study proves that ICM can detect serious arrhythmias in patients with moderate left ventricular dysfunction, but “we need to develop and test treatment paths.”
Dr. Aguiar considers SMART-MI an important study that “goes to the heart” of a common clinical dilemma.
“In clinical practice, we see patients with LVEF that is not that suppressed and so do not have a class I indication for ICM, but there are often features that might have you concerned and make you think it would be great if the LVEF was 35% or lower [to justify intervention],” Dr. Aguiar said.
Data provide insight on unaddressed risk group
SMART-MI confirms earlier evidence that post-MI patients with cardiac autonomic dysfunction are at high risk. Currently, this relative increase in risk goes “unaddressed,” according to Dr. Bauer. Although he contended that the risk itself “could be an indication for ICM in a high-risk patient group without classically defined left ventricular dysfunction,” he agreed that the ultimate value of this trial might be that it “opens a window” for a rationale to test preventive strategies.
An invited ESC discussant, Gerhard Hindricks, MD, PhD, praised the study for drawing attention to the risk of events in a subset of post-MI patients with LVEF of 35% or greater. However, he suggested that criteria other than those based on ECG might be more sensitive for selecting patients who might benefit from intervention.
“We do not know whether additional methods of establishing risk, such as imaging, might be valuable,” said Dr. Hindricks, chief of the department of arrhythmology in the Heart Institute of the University of Leipzig (Germany). He believes work in this area is needed to ensure appropriate entry criteria for interventional trials designed to modify risk in post-MI patients who do not meet the traditional definition of reduced ejection fraction.
Dr. Bauer reports financial relationships with Medtronic, which sponsored this study, as well as Bayer, Boehringer Ingelheim, Edwards, and Novartis. Dr. Aguiar reports no relevant financial conflicts.
FROM ESC CONGRESS 2021
Study evaluates OTC treatments for molluscum contagiosum
“It’s important for clinicians who see children with molluscum to be aware of the many products marketed to patients and to be able to provide objective information about them,” senior author Elaine Siegfried, MD, said in an interview following the annual meeting of the Society for Pediatric Dermatology, where the abstract was presented during a poster session.
In the text of their abstract, Dr. Siegfried, professor of pediatrics and dermatology at Saint Louis University, and coauthors Isaac Hoft, of Open Mind Holistics in Ft. Collins, Colo., and Samantha K. Ong, BA, a student at SLU, noted that MC primarily infects children, with an annual incidence of 8%. “Although the disease is self-limited, associated symptoms, contagion and an average 1-year duration prompt concern and frequent medical visits,” they wrote.
The optimal treatment for MC has not been defined and there is currently no approved medication approved for the condition, although three products are in development: VP-102 (cantharidin) by Verrica Pharmaceuticals; SB206, a topical antiviral by Novan; and 10%-15% KOH formulation by the Gurina Foundation.
But many OTC products have been marketed to treat the condition. To identify the OTC products and to assess accompanying information related to safety, efficacy, and cost, the researchers performed an internet search using the terms “molluscum” plus “treatment,” “treatment at home,” “relief,” and “medication.” Eight products were identified for analysis: Conzerol (Elroselabs), Molleave (Innovative Med), Mollenol (Jeva Laboratories), MolluscumBLAST (Revitalize Life Organics), Molluscum Away Patches (Molluscum Away), Naturasil (Nature’s Innovation), Terrasil (Advanced Skincare % Topical Solutions), and Zymaderm (Naturopathix). Package sizes ranged from 0.78 to 1.5 ounces, and prices ranged from about $19 to almost $55.
Dr. Siegfried and colleagues found that all products provided instructions on application and use but most package labels did not include sufficient information about their plant-based ingredients or appropriate dosing. Six of the eight products contained Thuja occidentalis (Arbor vitae), a coniferous cedar whose essential oil has been used in homeopathic products for its anti-inflammatory and antiviral properties. Lemon extract, tea tree oil, and other botanicals were present in no more than three products each. Only two of the products provided information about the number of lesions that could be treated per package.
“The lack of national oversight as well as robust methods for high-level data analysis make safety and efficacy unclear for a Thuja extract marketed to treat MC,” the researchers wrote. “Numerous adverse drug events and positive intradermal skin tests related to Thuja have been reported.”
Dr. Siegfried added that many OTC products offer a money-back guarantee, “so when seeing a patient who failed to respond to one of these products, encourage them, at least, to request a refund, but to also submit a comment about lack of efficacy, in order to provide more balanced Internet information.”
Dr. Siegfried disclosed that she has served as an investigator and consultant for Verrica Pharmaceuticals, and as a consultant and Data Safety Monitoring board member for Novan, two of the companies currently developing drugs to treat molluscum. Her coauthors had no conflicts of interest to disclose.
“It’s important for clinicians who see children with molluscum to be aware of the many products marketed to patients and to be able to provide objective information about them,” senior author Elaine Siegfried, MD, said in an interview following the annual meeting of the Society for Pediatric Dermatology, where the abstract was presented during a poster session.
In the text of their abstract, Dr. Siegfried, professor of pediatrics and dermatology at Saint Louis University, and coauthors Isaac Hoft, of Open Mind Holistics in Ft. Collins, Colo., and Samantha K. Ong, BA, a student at SLU, noted that MC primarily infects children, with an annual incidence of 8%. “Although the disease is self-limited, associated symptoms, contagion and an average 1-year duration prompt concern and frequent medical visits,” they wrote.
The optimal treatment for MC has not been defined and there is currently no approved medication approved for the condition, although three products are in development: VP-102 (cantharidin) by Verrica Pharmaceuticals; SB206, a topical antiviral by Novan; and 10%-15% KOH formulation by the Gurina Foundation.
But many OTC products have been marketed to treat the condition. To identify the OTC products and to assess accompanying information related to safety, efficacy, and cost, the researchers performed an internet search using the terms “molluscum” plus “treatment,” “treatment at home,” “relief,” and “medication.” Eight products were identified for analysis: Conzerol (Elroselabs), Molleave (Innovative Med), Mollenol (Jeva Laboratories), MolluscumBLAST (Revitalize Life Organics), Molluscum Away Patches (Molluscum Away), Naturasil (Nature’s Innovation), Terrasil (Advanced Skincare % Topical Solutions), and Zymaderm (Naturopathix). Package sizes ranged from 0.78 to 1.5 ounces, and prices ranged from about $19 to almost $55.
Dr. Siegfried and colleagues found that all products provided instructions on application and use but most package labels did not include sufficient information about their plant-based ingredients or appropriate dosing. Six of the eight products contained Thuja occidentalis (Arbor vitae), a coniferous cedar whose essential oil has been used in homeopathic products for its anti-inflammatory and antiviral properties. Lemon extract, tea tree oil, and other botanicals were present in no more than three products each. Only two of the products provided information about the number of lesions that could be treated per package.
“The lack of national oversight as well as robust methods for high-level data analysis make safety and efficacy unclear for a Thuja extract marketed to treat MC,” the researchers wrote. “Numerous adverse drug events and positive intradermal skin tests related to Thuja have been reported.”
Dr. Siegfried added that many OTC products offer a money-back guarantee, “so when seeing a patient who failed to respond to one of these products, encourage them, at least, to request a refund, but to also submit a comment about lack of efficacy, in order to provide more balanced Internet information.”
Dr. Siegfried disclosed that she has served as an investigator and consultant for Verrica Pharmaceuticals, and as a consultant and Data Safety Monitoring board member for Novan, two of the companies currently developing drugs to treat molluscum. Her coauthors had no conflicts of interest to disclose.
“It’s important for clinicians who see children with molluscum to be aware of the many products marketed to patients and to be able to provide objective information about them,” senior author Elaine Siegfried, MD, said in an interview following the annual meeting of the Society for Pediatric Dermatology, where the abstract was presented during a poster session.
In the text of their abstract, Dr. Siegfried, professor of pediatrics and dermatology at Saint Louis University, and coauthors Isaac Hoft, of Open Mind Holistics in Ft. Collins, Colo., and Samantha K. Ong, BA, a student at SLU, noted that MC primarily infects children, with an annual incidence of 8%. “Although the disease is self-limited, associated symptoms, contagion and an average 1-year duration prompt concern and frequent medical visits,” they wrote.
The optimal treatment for MC has not been defined and there is currently no approved medication approved for the condition, although three products are in development: VP-102 (cantharidin) by Verrica Pharmaceuticals; SB206, a topical antiviral by Novan; and 10%-15% KOH formulation by the Gurina Foundation.
But many OTC products have been marketed to treat the condition. To identify the OTC products and to assess accompanying information related to safety, efficacy, and cost, the researchers performed an internet search using the terms “molluscum” plus “treatment,” “treatment at home,” “relief,” and “medication.” Eight products were identified for analysis: Conzerol (Elroselabs), Molleave (Innovative Med), Mollenol (Jeva Laboratories), MolluscumBLAST (Revitalize Life Organics), Molluscum Away Patches (Molluscum Away), Naturasil (Nature’s Innovation), Terrasil (Advanced Skincare % Topical Solutions), and Zymaderm (Naturopathix). Package sizes ranged from 0.78 to 1.5 ounces, and prices ranged from about $19 to almost $55.
Dr. Siegfried and colleagues found that all products provided instructions on application and use but most package labels did not include sufficient information about their plant-based ingredients or appropriate dosing. Six of the eight products contained Thuja occidentalis (Arbor vitae), a coniferous cedar whose essential oil has been used in homeopathic products for its anti-inflammatory and antiviral properties. Lemon extract, tea tree oil, and other botanicals were present in no more than three products each. Only two of the products provided information about the number of lesions that could be treated per package.
“The lack of national oversight as well as robust methods for high-level data analysis make safety and efficacy unclear for a Thuja extract marketed to treat MC,” the researchers wrote. “Numerous adverse drug events and positive intradermal skin tests related to Thuja have been reported.”
Dr. Siegfried added that many OTC products offer a money-back guarantee, “so when seeing a patient who failed to respond to one of these products, encourage them, at least, to request a refund, but to also submit a comment about lack of efficacy, in order to provide more balanced Internet information.”
Dr. Siegfried disclosed that she has served as an investigator and consultant for Verrica Pharmaceuticals, and as a consultant and Data Safety Monitoring board member for Novan, two of the companies currently developing drugs to treat molluscum. Her coauthors had no conflicts of interest to disclose.
FROM SPD 2021
GUIDE-HF: CardioMEMS-guided meds fall short in mild to moderate heart failure
Medical therapy for heart failure guided by an implanted pulmonary artery pressure (PAP) sensor didn’t improve survival or risk for HF events like hospitalization over a year in a major randomized trial that entered a broad range of patients with mild to moderate disease.
But medical therapy adjustments based on PAP readings from the miniature CardioMEMS (Abbott) implant might well have surpassed conventional HF management for outcomes had the world not been turned upside down by SARS-CoV-2 and the pandemic lockdowns, assert researchers from the GUIDE-HF trial.
Something about the crisis, they concluded – although not without some pushback – led to better outcomes in the standard-care control group, apparently muddling any potential differences from those on PAP-guided management.
Working with regulators, the team conducted a “pre–COVID-19 impact analysis” that compared outcomes before the March 2020 national COVID-19 emergency declaration that forced much of the United States with shelter in place.
By that time, all of the trial’s patients had been followed for at least 3 months, and about three-fourths of its endpoints had already been counted, JoAnn Lindenfeld, MD, Vanderbilt University Medical Center, Nashville, Tenn., said at a media briefing prior to unveiling GUIDE-HF at the all-virtual European Society of Cardiology Congress 2021.
The pre–COVID-19 analysis, approved several months before the end of the trial – while the data were still blinded – had been “suggested by both regulatory agencies and professional societies in Europe and in the United States,” Dr. Lindenfeld said.
It pointed to a possible benefit for the CardioMEMS-guided strategy, a barely significant 19% drop in risk (P = .049) for the primary endpoint of death, HF hospitalization, or urgent HF hospital visit. The effect was driven by a 24% decline in HF events (P = .014), with no significant contribution from mortality.
“The benefits of hemodynamic monitoring and management in reducing heart failure hospitalizations extended to patients with less severe heart failure”; that is, those in New York Heart Association class 2 and any in NYHA class 3 with “elevated natriuretic peptides but no previous hospitalization,” said Dr. Lindenfeld, who is also lead author on the GUIDE-HF report published in the Lancet.
Such benefits would suggest that CardioMEMS-guided management can improve outcomes in an HF population much broader than the device’s current indication.
But as it happens, the trial’s prospectively defined 12-month primary outcomes were less impressive. A 12% decline in risk for the composite endpoint among patients managed by CardioMEMS failed to reach significance compared with standard management (P = .16).
“Several factors could explain the considerable loss of benefit of hemodynamic-guided management during the COVID-19 pandemic,” the Lancet report explained. They include “improved patient compliance with medical and dietary regimens, reduced respiratory infections, altered health-care provider behavior, changes in disease progression due to COVID-19, or other as yet unknown effects of a major pandemic.”
Expanded population
Importantly, GUIDE-HF had entered 1,000 patients in NYHA class 2-4 and either an HF hospitalization in the previous year or elevated natriuretic peptide levels. About 44% of the entrants in NYHA class 3 did not have a 1-year history of HF hospitalization.
That’s a more heterogeneous and potentially lower-risk cohort than patients in the randomized CHAMPION study of 11 years ago, which led to the implant’s approval on both sides of the Atlantic.
In that trial, CardioMEMS-guided management was followed by 30% drop in risk for HF hospitalization over 6 months (P < .001). But CHAMPION was limited to patients in NYHA class 3 with a history of HF hospitalization, the device’s current indication in both the United States and Europe.
The GUIDE-HF findings “reinforce that patients with class 3 heart failure and prior heart failure hospitalization are those in whom there is the clearest benefit, based on the prior CHAMPION trial. These are the patients where this monitoring strategy may be best targeted,” Gregg C. Fonarow, MD, University of California Los Angeles Medical Center, said in an interview.
Although GUIDE-HF didn’t show a significant benefit for NYHA class 2 patients with elevated biomarkers, who aren’t covered by the device’s current labeling, that group showed “some suggestions of potential benefit,” noted Dr. Fonarow, who isn’t a coauthor on the Lancet report. So, “there may be select patients with class 2 heart failure where monitoring could be considered on a case-by-case basis.”
In an interview, Larry A. Allen, MD, MHS, said that, “while the technology is pretty amazing, the real question is whether it tells us something that we didn’t already know that leads to improved care. Unfortunately, as tested here, it doesn’t, or at least not enough to make a big difference.”
The pre–COVID-19 impact analysis “should be interpreted with caution, and not as the primary finding,” Dr. Allen, from the University of Colorado at Denver, Aurora, who is not a GUIDE-HF coauthor, said in an interview.
One might hypothesize, he said, “that, in the setting of limited in-person visits with loss of physical examination, perhaps CardioMEMS would be more – not less – helpful during the pandemic. And yet the opposite was seen.”
The pandemic has “markedly altered all kinds of aspects of patient care and trial conduct, but that doesn’t make the data derived during that period uninformative,” Dr. Allen said. “And as we are increasingly reminded, the future will be a new normal, not a prepandemic normal.”
A third group
The GUIDE-HF trial includes, in addition to the 1,000 randomized patients, a single-group observational cohort of 2,600 patients, whose outcomes will be reported at another time, noted the published report.
But in the randomized comparison, conducted at 118 centers in North America, all patients were implanted with the CardioMEMS device and blinded as to their assigned strategy. Enrollment took place between March 2018 and Dec. 20, 2019.
Of the 1,000 successfully implanted patients, 497 were assigned to the pressure-guided strategy, in which “titration of diuretics was recommended if pulmonary artery pressure provided evidence of excess intravascular volume, and titration of vasodilators was recommended if elevated vascular resistance was evident,” the report stated.
The remaining 503 patients assigned to standard care served as control subjects, for whom “investigators were aware of treatment assignment but did not have access to PAP data.”
The hazard ratio for the primary endpoint in the pressure-guided group, compared with the control group, was 0.88 (95% confidence interval, 0.74-1.05; P = .16) over a median follow-up of 11.7 months.
But in the sensitivity analysis comparing outcomes before and after the COVID-19 lockdowns, using established methodology, the report stated, the primary-endpoint HR was 0.81 (95% CI, 0.66-1.00; P = .049).
The difference is owed to improved outcomes in the control group under pandemic conditions, the researchers concluded. Patients assigned to conventional management –whatever that meant during shelter-in-place – experienced 21% fewer primary-endpoint events than their own rate before the pandemic. After the COVID-19 emergency was declared, there was no significant difference in event rates between the two randomization groups.
In the primary 12-month analysis, the HR for HF events in the guided-therapy was not significant reduced, at 0.85 (95% CI, 0.70-1.03; P = .096). But in the pre-COVID-19 analysis, that risk fell significantly with CardioMEMS-guided management, for an HR of 0.76 (95% CI, 0.61-0.95; P = .014).
An editorial accompanying the GUIDE-HF publication (Lancet. 2021 Aug 27. doi: 10.1016/S0140-6736[21]01914-0) asserts that the trial “did not enroll an ideal group of patients for showing the efficacy of pulmonary artery pressure monitoring, since many had baseline pressures in the target range with little possibility of short-term gain.”
Also, wrote John G. F. Cleland, MD, PhD, University of Glasgow, and Pierpaolo Pellicori, MD, Imperial College London, “follow-up was too short, and interventions did not substantially change pulmonary artery pressure.”
They continue: “Monitoring alone cannot improve outcome, but consequent actions might. The GUIDE-HF results are encouraging but inconclusive, and should inform further research, possibly a large, simple, open-label trial to investigate a system of care rather than a single technology.”
GUIDE-HF was funded by Abbott. Dr. Lindenfeld disclosed receiving research grants from AstraZeneca, Sensible Medical, and Volumetrix; and consulting for Abbott, Alleviant Medical, AstraZeneca, Boehringer Ingelheim, Boston Scientific, CVRx, Edwards, Impulse Dynamics, and VWave. Dr. Fonarow reported consulting for Abbott and that his institution has participated in the GUIDE-HF trial; he has elsewhere disclosed consulting for Amgen, AstraZeneca, CHF Solutions Lifesciences, Janssen, Medtronic, and Novartis. Dr. Allen had elsewhere reported consulting for Abbott, Amgen, Boston Scientific, and Novartis. Dr. Cleland disclosed receiving personal fees from Abbott for serving on an advisory board for the MitraClip device, unrelated to the CardioMEMS device. Dr. Pellicori reported no relevant conflicts.
A version of this article first appeared on Medscape.com.
Medical therapy for heart failure guided by an implanted pulmonary artery pressure (PAP) sensor didn’t improve survival or risk for HF events like hospitalization over a year in a major randomized trial that entered a broad range of patients with mild to moderate disease.
But medical therapy adjustments based on PAP readings from the miniature CardioMEMS (Abbott) implant might well have surpassed conventional HF management for outcomes had the world not been turned upside down by SARS-CoV-2 and the pandemic lockdowns, assert researchers from the GUIDE-HF trial.
Something about the crisis, they concluded – although not without some pushback – led to better outcomes in the standard-care control group, apparently muddling any potential differences from those on PAP-guided management.
Working with regulators, the team conducted a “pre–COVID-19 impact analysis” that compared outcomes before the March 2020 national COVID-19 emergency declaration that forced much of the United States with shelter in place.
By that time, all of the trial’s patients had been followed for at least 3 months, and about three-fourths of its endpoints had already been counted, JoAnn Lindenfeld, MD, Vanderbilt University Medical Center, Nashville, Tenn., said at a media briefing prior to unveiling GUIDE-HF at the all-virtual European Society of Cardiology Congress 2021.
The pre–COVID-19 analysis, approved several months before the end of the trial – while the data were still blinded – had been “suggested by both regulatory agencies and professional societies in Europe and in the United States,” Dr. Lindenfeld said.
It pointed to a possible benefit for the CardioMEMS-guided strategy, a barely significant 19% drop in risk (P = .049) for the primary endpoint of death, HF hospitalization, or urgent HF hospital visit. The effect was driven by a 24% decline in HF events (P = .014), with no significant contribution from mortality.
“The benefits of hemodynamic monitoring and management in reducing heart failure hospitalizations extended to patients with less severe heart failure”; that is, those in New York Heart Association class 2 and any in NYHA class 3 with “elevated natriuretic peptides but no previous hospitalization,” said Dr. Lindenfeld, who is also lead author on the GUIDE-HF report published in the Lancet.
Such benefits would suggest that CardioMEMS-guided management can improve outcomes in an HF population much broader than the device’s current indication.
But as it happens, the trial’s prospectively defined 12-month primary outcomes were less impressive. A 12% decline in risk for the composite endpoint among patients managed by CardioMEMS failed to reach significance compared with standard management (P = .16).
“Several factors could explain the considerable loss of benefit of hemodynamic-guided management during the COVID-19 pandemic,” the Lancet report explained. They include “improved patient compliance with medical and dietary regimens, reduced respiratory infections, altered health-care provider behavior, changes in disease progression due to COVID-19, or other as yet unknown effects of a major pandemic.”
Expanded population
Importantly, GUIDE-HF had entered 1,000 patients in NYHA class 2-4 and either an HF hospitalization in the previous year or elevated natriuretic peptide levels. About 44% of the entrants in NYHA class 3 did not have a 1-year history of HF hospitalization.
That’s a more heterogeneous and potentially lower-risk cohort than patients in the randomized CHAMPION study of 11 years ago, which led to the implant’s approval on both sides of the Atlantic.
In that trial, CardioMEMS-guided management was followed by 30% drop in risk for HF hospitalization over 6 months (P < .001). But CHAMPION was limited to patients in NYHA class 3 with a history of HF hospitalization, the device’s current indication in both the United States and Europe.
The GUIDE-HF findings “reinforce that patients with class 3 heart failure and prior heart failure hospitalization are those in whom there is the clearest benefit, based on the prior CHAMPION trial. These are the patients where this monitoring strategy may be best targeted,” Gregg C. Fonarow, MD, University of California Los Angeles Medical Center, said in an interview.
Although GUIDE-HF didn’t show a significant benefit for NYHA class 2 patients with elevated biomarkers, who aren’t covered by the device’s current labeling, that group showed “some suggestions of potential benefit,” noted Dr. Fonarow, who isn’t a coauthor on the Lancet report. So, “there may be select patients with class 2 heart failure where monitoring could be considered on a case-by-case basis.”
In an interview, Larry A. Allen, MD, MHS, said that, “while the technology is pretty amazing, the real question is whether it tells us something that we didn’t already know that leads to improved care. Unfortunately, as tested here, it doesn’t, or at least not enough to make a big difference.”
The pre–COVID-19 impact analysis “should be interpreted with caution, and not as the primary finding,” Dr. Allen, from the University of Colorado at Denver, Aurora, who is not a GUIDE-HF coauthor, said in an interview.
One might hypothesize, he said, “that, in the setting of limited in-person visits with loss of physical examination, perhaps CardioMEMS would be more – not less – helpful during the pandemic. And yet the opposite was seen.”
The pandemic has “markedly altered all kinds of aspects of patient care and trial conduct, but that doesn’t make the data derived during that period uninformative,” Dr. Allen said. “And as we are increasingly reminded, the future will be a new normal, not a prepandemic normal.”
A third group
The GUIDE-HF trial includes, in addition to the 1,000 randomized patients, a single-group observational cohort of 2,600 patients, whose outcomes will be reported at another time, noted the published report.
But in the randomized comparison, conducted at 118 centers in North America, all patients were implanted with the CardioMEMS device and blinded as to their assigned strategy. Enrollment took place between March 2018 and Dec. 20, 2019.
Of the 1,000 successfully implanted patients, 497 were assigned to the pressure-guided strategy, in which “titration of diuretics was recommended if pulmonary artery pressure provided evidence of excess intravascular volume, and titration of vasodilators was recommended if elevated vascular resistance was evident,” the report stated.
The remaining 503 patients assigned to standard care served as control subjects, for whom “investigators were aware of treatment assignment but did not have access to PAP data.”
The hazard ratio for the primary endpoint in the pressure-guided group, compared with the control group, was 0.88 (95% confidence interval, 0.74-1.05; P = .16) over a median follow-up of 11.7 months.
But in the sensitivity analysis comparing outcomes before and after the COVID-19 lockdowns, using established methodology, the report stated, the primary-endpoint HR was 0.81 (95% CI, 0.66-1.00; P = .049).
The difference is owed to improved outcomes in the control group under pandemic conditions, the researchers concluded. Patients assigned to conventional management –whatever that meant during shelter-in-place – experienced 21% fewer primary-endpoint events than their own rate before the pandemic. After the COVID-19 emergency was declared, there was no significant difference in event rates between the two randomization groups.
In the primary 12-month analysis, the HR for HF events in the guided-therapy was not significant reduced, at 0.85 (95% CI, 0.70-1.03; P = .096). But in the pre-COVID-19 analysis, that risk fell significantly with CardioMEMS-guided management, for an HR of 0.76 (95% CI, 0.61-0.95; P = .014).
An editorial accompanying the GUIDE-HF publication (Lancet. 2021 Aug 27. doi: 10.1016/S0140-6736[21]01914-0) asserts that the trial “did not enroll an ideal group of patients for showing the efficacy of pulmonary artery pressure monitoring, since many had baseline pressures in the target range with little possibility of short-term gain.”
Also, wrote John G. F. Cleland, MD, PhD, University of Glasgow, and Pierpaolo Pellicori, MD, Imperial College London, “follow-up was too short, and interventions did not substantially change pulmonary artery pressure.”
They continue: “Monitoring alone cannot improve outcome, but consequent actions might. The GUIDE-HF results are encouraging but inconclusive, and should inform further research, possibly a large, simple, open-label trial to investigate a system of care rather than a single technology.”
GUIDE-HF was funded by Abbott. Dr. Lindenfeld disclosed receiving research grants from AstraZeneca, Sensible Medical, and Volumetrix; and consulting for Abbott, Alleviant Medical, AstraZeneca, Boehringer Ingelheim, Boston Scientific, CVRx, Edwards, Impulse Dynamics, and VWave. Dr. Fonarow reported consulting for Abbott and that his institution has participated in the GUIDE-HF trial; he has elsewhere disclosed consulting for Amgen, AstraZeneca, CHF Solutions Lifesciences, Janssen, Medtronic, and Novartis. Dr. Allen had elsewhere reported consulting for Abbott, Amgen, Boston Scientific, and Novartis. Dr. Cleland disclosed receiving personal fees from Abbott for serving on an advisory board for the MitraClip device, unrelated to the CardioMEMS device. Dr. Pellicori reported no relevant conflicts.
A version of this article first appeared on Medscape.com.
Medical therapy for heart failure guided by an implanted pulmonary artery pressure (PAP) sensor didn’t improve survival or risk for HF events like hospitalization over a year in a major randomized trial that entered a broad range of patients with mild to moderate disease.
But medical therapy adjustments based on PAP readings from the miniature CardioMEMS (Abbott) implant might well have surpassed conventional HF management for outcomes had the world not been turned upside down by SARS-CoV-2 and the pandemic lockdowns, assert researchers from the GUIDE-HF trial.
Something about the crisis, they concluded – although not without some pushback – led to better outcomes in the standard-care control group, apparently muddling any potential differences from those on PAP-guided management.
Working with regulators, the team conducted a “pre–COVID-19 impact analysis” that compared outcomes before the March 2020 national COVID-19 emergency declaration that forced much of the United States with shelter in place.
By that time, all of the trial’s patients had been followed for at least 3 months, and about three-fourths of its endpoints had already been counted, JoAnn Lindenfeld, MD, Vanderbilt University Medical Center, Nashville, Tenn., said at a media briefing prior to unveiling GUIDE-HF at the all-virtual European Society of Cardiology Congress 2021.
The pre–COVID-19 analysis, approved several months before the end of the trial – while the data were still blinded – had been “suggested by both regulatory agencies and professional societies in Europe and in the United States,” Dr. Lindenfeld said.
It pointed to a possible benefit for the CardioMEMS-guided strategy, a barely significant 19% drop in risk (P = .049) for the primary endpoint of death, HF hospitalization, or urgent HF hospital visit. The effect was driven by a 24% decline in HF events (P = .014), with no significant contribution from mortality.
“The benefits of hemodynamic monitoring and management in reducing heart failure hospitalizations extended to patients with less severe heart failure”; that is, those in New York Heart Association class 2 and any in NYHA class 3 with “elevated natriuretic peptides but no previous hospitalization,” said Dr. Lindenfeld, who is also lead author on the GUIDE-HF report published in the Lancet.
Such benefits would suggest that CardioMEMS-guided management can improve outcomes in an HF population much broader than the device’s current indication.
But as it happens, the trial’s prospectively defined 12-month primary outcomes were less impressive. A 12% decline in risk for the composite endpoint among patients managed by CardioMEMS failed to reach significance compared with standard management (P = .16).
“Several factors could explain the considerable loss of benefit of hemodynamic-guided management during the COVID-19 pandemic,” the Lancet report explained. They include “improved patient compliance with medical and dietary regimens, reduced respiratory infections, altered health-care provider behavior, changes in disease progression due to COVID-19, or other as yet unknown effects of a major pandemic.”
Expanded population
Importantly, GUIDE-HF had entered 1,000 patients in NYHA class 2-4 and either an HF hospitalization in the previous year or elevated natriuretic peptide levels. About 44% of the entrants in NYHA class 3 did not have a 1-year history of HF hospitalization.
That’s a more heterogeneous and potentially lower-risk cohort than patients in the randomized CHAMPION study of 11 years ago, which led to the implant’s approval on both sides of the Atlantic.
In that trial, CardioMEMS-guided management was followed by 30% drop in risk for HF hospitalization over 6 months (P < .001). But CHAMPION was limited to patients in NYHA class 3 with a history of HF hospitalization, the device’s current indication in both the United States and Europe.
The GUIDE-HF findings “reinforce that patients with class 3 heart failure and prior heart failure hospitalization are those in whom there is the clearest benefit, based on the prior CHAMPION trial. These are the patients where this monitoring strategy may be best targeted,” Gregg C. Fonarow, MD, University of California Los Angeles Medical Center, said in an interview.
Although GUIDE-HF didn’t show a significant benefit for NYHA class 2 patients with elevated biomarkers, who aren’t covered by the device’s current labeling, that group showed “some suggestions of potential benefit,” noted Dr. Fonarow, who isn’t a coauthor on the Lancet report. So, “there may be select patients with class 2 heart failure where monitoring could be considered on a case-by-case basis.”
In an interview, Larry A. Allen, MD, MHS, said that, “while the technology is pretty amazing, the real question is whether it tells us something that we didn’t already know that leads to improved care. Unfortunately, as tested here, it doesn’t, or at least not enough to make a big difference.”
The pre–COVID-19 impact analysis “should be interpreted with caution, and not as the primary finding,” Dr. Allen, from the University of Colorado at Denver, Aurora, who is not a GUIDE-HF coauthor, said in an interview.
One might hypothesize, he said, “that, in the setting of limited in-person visits with loss of physical examination, perhaps CardioMEMS would be more – not less – helpful during the pandemic. And yet the opposite was seen.”
The pandemic has “markedly altered all kinds of aspects of patient care and trial conduct, but that doesn’t make the data derived during that period uninformative,” Dr. Allen said. “And as we are increasingly reminded, the future will be a new normal, not a prepandemic normal.”
A third group
The GUIDE-HF trial includes, in addition to the 1,000 randomized patients, a single-group observational cohort of 2,600 patients, whose outcomes will be reported at another time, noted the published report.
But in the randomized comparison, conducted at 118 centers in North America, all patients were implanted with the CardioMEMS device and blinded as to their assigned strategy. Enrollment took place between March 2018 and Dec. 20, 2019.
Of the 1,000 successfully implanted patients, 497 were assigned to the pressure-guided strategy, in which “titration of diuretics was recommended if pulmonary artery pressure provided evidence of excess intravascular volume, and titration of vasodilators was recommended if elevated vascular resistance was evident,” the report stated.
The remaining 503 patients assigned to standard care served as control subjects, for whom “investigators were aware of treatment assignment but did not have access to PAP data.”
The hazard ratio for the primary endpoint in the pressure-guided group, compared with the control group, was 0.88 (95% confidence interval, 0.74-1.05; P = .16) over a median follow-up of 11.7 months.
But in the sensitivity analysis comparing outcomes before and after the COVID-19 lockdowns, using established methodology, the report stated, the primary-endpoint HR was 0.81 (95% CI, 0.66-1.00; P = .049).
The difference is owed to improved outcomes in the control group under pandemic conditions, the researchers concluded. Patients assigned to conventional management –whatever that meant during shelter-in-place – experienced 21% fewer primary-endpoint events than their own rate before the pandemic. After the COVID-19 emergency was declared, there was no significant difference in event rates between the two randomization groups.
In the primary 12-month analysis, the HR for HF events in the guided-therapy was not significant reduced, at 0.85 (95% CI, 0.70-1.03; P = .096). But in the pre-COVID-19 analysis, that risk fell significantly with CardioMEMS-guided management, for an HR of 0.76 (95% CI, 0.61-0.95; P = .014).
An editorial accompanying the GUIDE-HF publication (Lancet. 2021 Aug 27. doi: 10.1016/S0140-6736[21]01914-0) asserts that the trial “did not enroll an ideal group of patients for showing the efficacy of pulmonary artery pressure monitoring, since many had baseline pressures in the target range with little possibility of short-term gain.”
Also, wrote John G. F. Cleland, MD, PhD, University of Glasgow, and Pierpaolo Pellicori, MD, Imperial College London, “follow-up was too short, and interventions did not substantially change pulmonary artery pressure.”
They continue: “Monitoring alone cannot improve outcome, but consequent actions might. The GUIDE-HF results are encouraging but inconclusive, and should inform further research, possibly a large, simple, open-label trial to investigate a system of care rather than a single technology.”
GUIDE-HF was funded by Abbott. Dr. Lindenfeld disclosed receiving research grants from AstraZeneca, Sensible Medical, and Volumetrix; and consulting for Abbott, Alleviant Medical, AstraZeneca, Boehringer Ingelheim, Boston Scientific, CVRx, Edwards, Impulse Dynamics, and VWave. Dr. Fonarow reported consulting for Abbott and that his institution has participated in the GUIDE-HF trial; he has elsewhere disclosed consulting for Amgen, AstraZeneca, CHF Solutions Lifesciences, Janssen, Medtronic, and Novartis. Dr. Allen had elsewhere reported consulting for Abbott, Amgen, Boston Scientific, and Novartis. Dr. Cleland disclosed receiving personal fees from Abbott for serving on an advisory board for the MitraClip device, unrelated to the CardioMEMS device. Dr. Pellicori reported no relevant conflicts.
A version of this article first appeared on Medscape.com.
Aerobic exercise can reduce AFib frequency, severity: ACTIVE-AF
Patients with atrial fibrillation (AFib) gained significant benefits from a 6-month program of supervised and unsupervised moderate exercise versus usual care, new randomized trial results show.
Among 120 AFib patients in the ACTIVE-AF trial, those randomized to the exercise arm had significantly less frequent AFib recurrence and less severe symptoms over a 1-year period, said Adrian Elliott, PhD, who will present this late-breaking research at the European Society of Cardiology (ESC) Congress 2021.
The trial “demonstrates that some patients can control their arrhythmia through physical activity, without the need for complex interventions such as ablation or medications to keep their heart in normal rhythm,” Dr. Elliott, from the University of Adelaide, Australia, said in a statement from the ESC.
This is “the largest randomized controlled trial investigating the value of an exercise prescription in patients with symptomatic paroxysmal or persistent [AFib],” he told this news organization in an email.
The findings “really provide the evidence needed that recommending aerobic exercise in patients with symptomatic AFib can lower the severity of symptoms and prevent the recurrence of AFib for many patients,” he said. Aerobic exercise should be incorporated into patient treatment, he added, “alongside the use of medications, as guided by a cardiologist, and management of obesity, hypertension, and sleep apnea.”
Mina K. Chung, MD, lead author of a Scientific Statement from the American Heart Association on Lifestyle and Risk Factor Modification for Reduction of Atrial Fibrillation, as previously reported, agrees.
The “findings support the AHA Scientific Statement that we should encourage our patients with AFib to include regular moderate exercise to help prevent AFib, reduce AFib burden, and improve AFib-related symptoms and quality of life,” Dr. Chung, a cardiologist at the Cleveland Clinic, summarized in an email.
“Our recommendation is to encourage AFib patients to aim for at least the AHA physical activity guidelines for the general population, which advise 150 minutes each week of moderate-intensity exercise,” Dr. Chung said.
This is a “reasonable” goal, but “some might argue that a slightly higher target of physical activity duration may be considered,” Dr. Elliott commented.
ACTIVE-AF, he noted, suggests that “as a general guide, patients [with AFib] should strive to build up to 3.5 hours per week of aerobic exercise and incorporate some higher intensity activities to improve cardiorespiratory fitness.”
Aim for 3.5 hours a week
A previous observational study showed that patients who improved their cardiorespiratory fitness over a 5-year period were significantly less likely to have AFib recurrences.
And in a randomized trial of 51 patients, 12 weeks of aerobic interval training reduced the time spent in AFib compared to usual care, during a 4-week follow-up.
ACTIVE-AF aimed to investigate the value of exercise in AFib in a larger, longer, randomized trial.
The researchers enrolled 120 patients with an average age of 65 years, of whom 43% were women.
Patients in the treatment group received individualized guided exercise from an exercise physiologist in the cardiology clinic once a week for 3 months, then every second week for the following 3 months along with a physical activity plan to follow at home for the other days – aiming to build up to 3.5 hours of physical activity a week.
The supervised sessions, Dr. Elliott explained, were typically higher intensity to raise cardiorespiratory fitness, while the home-based exercise was a moderate intensity aerobic activity of the patient’s choice, such as walking, indoor cycling, or swimming.
“We certainly cautioned against far exceeding this level,” he added.
Patients in the usual care group received exercise advice but no active intervention.
All patients received usual medical care from their cardiologist, who was blinded to the study group allocation.
The co-primary outcomes were AFib symptom severity score and the percentage of patients with recurrent AFib at 12 months, defined as having an AFib episode that lasted longer than 30 seconds or undergoing ablation or requiring ongoing anti-arrhythmic drug therapy.
At 12 months, the percentage of patients with AFib recurrence was significantly lower in the exercise group than in the control group (60% vs. 80%; hazard ratio, 0.50; 95% confidence interval, 0.33-0.78; P = .002).
This means that more patients in the exercise group had a normal heart rhythm without needing an invasive intervention (ablation) or continued use of drugs, Dr. Elliott stressed.
Patients in the exercise group also had significantly less severe symptoms – palpitations, shortness of breath, and fatigue – than patients in the control group.
“On average, patients were achieving close to 180 minutes [of physical activity] per week by 6 months of the intervention and attended 18 supervised sessions in the clinic,” Dr. Elliott said.
Cost was not a barrier since the sessions with an exercise physiologist were free.
Lack of time was the most common reason for missing the physical activity targets, especially for patients with work and family commitments.
Most patients liked the variety of physical activity options.
The researchers plan to determine any gender differences in ACTIVE-AF.
Further research is needed, Dr. Elliott added, to determine which type of exercise is best, whether exercise plus weight loss is synergistic, and whether exercise leads to better long-term freedom from arrhythmia, reduced hospitalization, and improved survival.
The study was partially supported by the National Heart Foundation of Australia through a postdoctoral fellowship to Dr. Elliott. The researchers and Dr. Chung have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Patients with atrial fibrillation (AFib) gained significant benefits from a 6-month program of supervised and unsupervised moderate exercise versus usual care, new randomized trial results show.
Among 120 AFib patients in the ACTIVE-AF trial, those randomized to the exercise arm had significantly less frequent AFib recurrence and less severe symptoms over a 1-year period, said Adrian Elliott, PhD, who will present this late-breaking research at the European Society of Cardiology (ESC) Congress 2021.
The trial “demonstrates that some patients can control their arrhythmia through physical activity, without the need for complex interventions such as ablation or medications to keep their heart in normal rhythm,” Dr. Elliott, from the University of Adelaide, Australia, said in a statement from the ESC.
This is “the largest randomized controlled trial investigating the value of an exercise prescription in patients with symptomatic paroxysmal or persistent [AFib],” he told this news organization in an email.
The findings “really provide the evidence needed that recommending aerobic exercise in patients with symptomatic AFib can lower the severity of symptoms and prevent the recurrence of AFib for many patients,” he said. Aerobic exercise should be incorporated into patient treatment, he added, “alongside the use of medications, as guided by a cardiologist, and management of obesity, hypertension, and sleep apnea.”
Mina K. Chung, MD, lead author of a Scientific Statement from the American Heart Association on Lifestyle and Risk Factor Modification for Reduction of Atrial Fibrillation, as previously reported, agrees.
The “findings support the AHA Scientific Statement that we should encourage our patients with AFib to include regular moderate exercise to help prevent AFib, reduce AFib burden, and improve AFib-related symptoms and quality of life,” Dr. Chung, a cardiologist at the Cleveland Clinic, summarized in an email.
“Our recommendation is to encourage AFib patients to aim for at least the AHA physical activity guidelines for the general population, which advise 150 minutes each week of moderate-intensity exercise,” Dr. Chung said.
This is a “reasonable” goal, but “some might argue that a slightly higher target of physical activity duration may be considered,” Dr. Elliott commented.
ACTIVE-AF, he noted, suggests that “as a general guide, patients [with AFib] should strive to build up to 3.5 hours per week of aerobic exercise and incorporate some higher intensity activities to improve cardiorespiratory fitness.”
Aim for 3.5 hours a week
A previous observational study showed that patients who improved their cardiorespiratory fitness over a 5-year period were significantly less likely to have AFib recurrences.
And in a randomized trial of 51 patients, 12 weeks of aerobic interval training reduced the time spent in AFib compared to usual care, during a 4-week follow-up.
ACTIVE-AF aimed to investigate the value of exercise in AFib in a larger, longer, randomized trial.
The researchers enrolled 120 patients with an average age of 65 years, of whom 43% were women.
Patients in the treatment group received individualized guided exercise from an exercise physiologist in the cardiology clinic once a week for 3 months, then every second week for the following 3 months along with a physical activity plan to follow at home for the other days – aiming to build up to 3.5 hours of physical activity a week.
The supervised sessions, Dr. Elliott explained, were typically higher intensity to raise cardiorespiratory fitness, while the home-based exercise was a moderate intensity aerobic activity of the patient’s choice, such as walking, indoor cycling, or swimming.
“We certainly cautioned against far exceeding this level,” he added.
Patients in the usual care group received exercise advice but no active intervention.
All patients received usual medical care from their cardiologist, who was blinded to the study group allocation.
The co-primary outcomes were AFib symptom severity score and the percentage of patients with recurrent AFib at 12 months, defined as having an AFib episode that lasted longer than 30 seconds or undergoing ablation or requiring ongoing anti-arrhythmic drug therapy.
At 12 months, the percentage of patients with AFib recurrence was significantly lower in the exercise group than in the control group (60% vs. 80%; hazard ratio, 0.50; 95% confidence interval, 0.33-0.78; P = .002).
This means that more patients in the exercise group had a normal heart rhythm without needing an invasive intervention (ablation) or continued use of drugs, Dr. Elliott stressed.
Patients in the exercise group also had significantly less severe symptoms – palpitations, shortness of breath, and fatigue – than patients in the control group.
“On average, patients were achieving close to 180 minutes [of physical activity] per week by 6 months of the intervention and attended 18 supervised sessions in the clinic,” Dr. Elliott said.
Cost was not a barrier since the sessions with an exercise physiologist were free.
Lack of time was the most common reason for missing the physical activity targets, especially for patients with work and family commitments.
Most patients liked the variety of physical activity options.
The researchers plan to determine any gender differences in ACTIVE-AF.
Further research is needed, Dr. Elliott added, to determine which type of exercise is best, whether exercise plus weight loss is synergistic, and whether exercise leads to better long-term freedom from arrhythmia, reduced hospitalization, and improved survival.
The study was partially supported by the National Heart Foundation of Australia through a postdoctoral fellowship to Dr. Elliott. The researchers and Dr. Chung have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Patients with atrial fibrillation (AFib) gained significant benefits from a 6-month program of supervised and unsupervised moderate exercise versus usual care, new randomized trial results show.
Among 120 AFib patients in the ACTIVE-AF trial, those randomized to the exercise arm had significantly less frequent AFib recurrence and less severe symptoms over a 1-year period, said Adrian Elliott, PhD, who will present this late-breaking research at the European Society of Cardiology (ESC) Congress 2021.
The trial “demonstrates that some patients can control their arrhythmia through physical activity, without the need for complex interventions such as ablation or medications to keep their heart in normal rhythm,” Dr. Elliott, from the University of Adelaide, Australia, said in a statement from the ESC.
This is “the largest randomized controlled trial investigating the value of an exercise prescription in patients with symptomatic paroxysmal or persistent [AFib],” he told this news organization in an email.
The findings “really provide the evidence needed that recommending aerobic exercise in patients with symptomatic AFib can lower the severity of symptoms and prevent the recurrence of AFib for many patients,” he said. Aerobic exercise should be incorporated into patient treatment, he added, “alongside the use of medications, as guided by a cardiologist, and management of obesity, hypertension, and sleep apnea.”
Mina K. Chung, MD, lead author of a Scientific Statement from the American Heart Association on Lifestyle and Risk Factor Modification for Reduction of Atrial Fibrillation, as previously reported, agrees.
The “findings support the AHA Scientific Statement that we should encourage our patients with AFib to include regular moderate exercise to help prevent AFib, reduce AFib burden, and improve AFib-related symptoms and quality of life,” Dr. Chung, a cardiologist at the Cleveland Clinic, summarized in an email.
“Our recommendation is to encourage AFib patients to aim for at least the AHA physical activity guidelines for the general population, which advise 150 minutes each week of moderate-intensity exercise,” Dr. Chung said.
This is a “reasonable” goal, but “some might argue that a slightly higher target of physical activity duration may be considered,” Dr. Elliott commented.
ACTIVE-AF, he noted, suggests that “as a general guide, patients [with AFib] should strive to build up to 3.5 hours per week of aerobic exercise and incorporate some higher intensity activities to improve cardiorespiratory fitness.”
Aim for 3.5 hours a week
A previous observational study showed that patients who improved their cardiorespiratory fitness over a 5-year period were significantly less likely to have AFib recurrences.
And in a randomized trial of 51 patients, 12 weeks of aerobic interval training reduced the time spent in AFib compared to usual care, during a 4-week follow-up.
ACTIVE-AF aimed to investigate the value of exercise in AFib in a larger, longer, randomized trial.
The researchers enrolled 120 patients with an average age of 65 years, of whom 43% were women.
Patients in the treatment group received individualized guided exercise from an exercise physiologist in the cardiology clinic once a week for 3 months, then every second week for the following 3 months along with a physical activity plan to follow at home for the other days – aiming to build up to 3.5 hours of physical activity a week.
The supervised sessions, Dr. Elliott explained, were typically higher intensity to raise cardiorespiratory fitness, while the home-based exercise was a moderate intensity aerobic activity of the patient’s choice, such as walking, indoor cycling, or swimming.
“We certainly cautioned against far exceeding this level,” he added.
Patients in the usual care group received exercise advice but no active intervention.
All patients received usual medical care from their cardiologist, who was blinded to the study group allocation.
The co-primary outcomes were AFib symptom severity score and the percentage of patients with recurrent AFib at 12 months, defined as having an AFib episode that lasted longer than 30 seconds or undergoing ablation or requiring ongoing anti-arrhythmic drug therapy.
At 12 months, the percentage of patients with AFib recurrence was significantly lower in the exercise group than in the control group (60% vs. 80%; hazard ratio, 0.50; 95% confidence interval, 0.33-0.78; P = .002).
This means that more patients in the exercise group had a normal heart rhythm without needing an invasive intervention (ablation) or continued use of drugs, Dr. Elliott stressed.
Patients in the exercise group also had significantly less severe symptoms – palpitations, shortness of breath, and fatigue – than patients in the control group.
“On average, patients were achieving close to 180 minutes [of physical activity] per week by 6 months of the intervention and attended 18 supervised sessions in the clinic,” Dr. Elliott said.
Cost was not a barrier since the sessions with an exercise physiologist were free.
Lack of time was the most common reason for missing the physical activity targets, especially for patients with work and family commitments.
Most patients liked the variety of physical activity options.
The researchers plan to determine any gender differences in ACTIVE-AF.
Further research is needed, Dr. Elliott added, to determine which type of exercise is best, whether exercise plus weight loss is synergistic, and whether exercise leads to better long-term freedom from arrhythmia, reduced hospitalization, and improved survival.
The study was partially supported by the National Heart Foundation of Australia through a postdoctoral fellowship to Dr. Elliott. The researchers and Dr. Chung have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
EAACI review urges reduction in antibiotic overuse with allergy
Urgent recommendations from a European Academy of Allergy and Clinical Immunology (EAACI) task force are aimed at reducing antibiotic overuse with allergic disease.
Top recommendations include limiting antibiotic therapy in pregnancy and early childhood to help reduce the allergy epidemic in children, and restricting antibiotic therapy in exacerbations and chronic treatment of allergic diseases, especially asthma and atopic dermatitis.
The review, by lead author Gerdien Tramper-Stranders, MD, PhD, department of pediatrics, Franciscus Gasthuis & Vlietland Hospital, Rotterdam, the Netherlands, and colleagues, was published online Aug. 13 in the journal Allergy.
Several studies have shown that use of antibiotics in childhood and during pregnancy is associated with disturbing the intestinal and respiratory microbiome, which in turn leads to dysbiosis and an increased risk of acquiring allergic diseases, the authors noted.
In addition, patients with allergic diseases such as asthma have a higher risk of being prescribed antibiotics for infections compared with the general population, despite lack of clear clinical benefit.
“In fact, there are no clear data supporting antibiotic prescriptions for acute exacerbations; and clinical and/or laboratory criteria are lacking,” the authors wrote.
Despite that lack of data, antibiotics are often prescribed for exacerbations along with oral corticosteroids, Dr. Tramper-Stranders said in an interview. Some patients may benefit from antibiotics in a flare-up, she said, but more research is needed to determine which ones.
Dr. Tramper-Stranders said Franciscus has begun a large study that includes patients with asthma exacerbations to find biomarkers that might predict the type or origin of exacerbation to personalize treatment.
Recommendations have global relevance
She said although the recommendations are coming from the EAACI group, they apply worldwide.
“Especially in countries outside Northern Europe, antibiotic use is tremendous, leading to high rates of antibiotic resistance; but also increasing the risk for developing allergic diseases when prescribed in infancy,” she said.
She pointed out that in the United States, as many as one in six children receive unnecessary antibiotics for an asthma exacerbation. Overtreatment in adults with flare-ups is also prevalent, at rates from 40%-50%.
Millie Kwan, MD, PhD, an allergy specialist at University of North Carolina in Chapel Hill, said in an interview that in the U.S. there’s been a culture change in the direction of antibiotic restraint – but there are still problems.
“It’s a lot easier for us to whip out our prescription pads and prescribe antibiotics for an asthma patient who’s having a flare-up or a patient who has atopic dermatitis before addressing the underlying mechanism directly,” Dr. Kwan said. She agreed that antibiotic overuse is prevalent in pregnancies in the U.S., and she said that starts with the high prevalence of cesarean births. Nearly one-third of all births in the U.S. are by C-section, twice the rate recommended by the World Health Organization.
“Just bypassing the birth canal actually changes what kind of microflora the infant is being exposed to,” Dr. Kwan said. “That’s the first huge problem.”
The second problem, she said, is the potential for overuse of antibiotics with the surgical procedure.
The researchers wrote that pre-, pro- or postbiotics might alter the course of allergic disease, but clear evidence is lacking.
Until now, Dr. Tramper-Stranders said, pre- or probiotic treatment in infancy, irrespective of previous antibiotic use, has not proved effective in preventing allergies.
Data describing the effect of pre- or probiotics after an antibiotic course are scarce, are limited to older children and adults, and are focused on short-term effects, such as diarrhea prevention, she explained.
Dr. Kwan says she agrees that current data are not strong enough to recommend one over another.
“We don’t even know what the normal amount of bacteria should be to constitute an environment where the immune system develops ‘normally,’ “ she said.
Antibiotics should be prescribed cautiously and by following current recommendations to use the narrowest spectrum available, the authors wrote. Future research in antibiotic stewardship should incorporate biomarker-guided therapy to determine which patients might benefit most from antibiotic therapy.
“Practicing antibiotic stewardship needs recurrent attention and we hope that with this initiative, we specifically reach allergy doctors who will rethink their next [antibiotic] prescription. Within our EAACI task force, we will next work on a guideline for rational antibiotic use in asthma,” Dr. Tramper-Stranders said.
The review’s authors and Dr. Kwan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Urgent recommendations from a European Academy of Allergy and Clinical Immunology (EAACI) task force are aimed at reducing antibiotic overuse with allergic disease.
Top recommendations include limiting antibiotic therapy in pregnancy and early childhood to help reduce the allergy epidemic in children, and restricting antibiotic therapy in exacerbations and chronic treatment of allergic diseases, especially asthma and atopic dermatitis.
The review, by lead author Gerdien Tramper-Stranders, MD, PhD, department of pediatrics, Franciscus Gasthuis & Vlietland Hospital, Rotterdam, the Netherlands, and colleagues, was published online Aug. 13 in the journal Allergy.
Several studies have shown that use of antibiotics in childhood and during pregnancy is associated with disturbing the intestinal and respiratory microbiome, which in turn leads to dysbiosis and an increased risk of acquiring allergic diseases, the authors noted.
In addition, patients with allergic diseases such as asthma have a higher risk of being prescribed antibiotics for infections compared with the general population, despite lack of clear clinical benefit.
“In fact, there are no clear data supporting antibiotic prescriptions for acute exacerbations; and clinical and/or laboratory criteria are lacking,” the authors wrote.
Despite that lack of data, antibiotics are often prescribed for exacerbations along with oral corticosteroids, Dr. Tramper-Stranders said in an interview. Some patients may benefit from antibiotics in a flare-up, she said, but more research is needed to determine which ones.
Dr. Tramper-Stranders said Franciscus has begun a large study that includes patients with asthma exacerbations to find biomarkers that might predict the type or origin of exacerbation to personalize treatment.
Recommendations have global relevance
She said although the recommendations are coming from the EAACI group, they apply worldwide.
“Especially in countries outside Northern Europe, antibiotic use is tremendous, leading to high rates of antibiotic resistance; but also increasing the risk for developing allergic diseases when prescribed in infancy,” she said.
She pointed out that in the United States, as many as one in six children receive unnecessary antibiotics for an asthma exacerbation. Overtreatment in adults with flare-ups is also prevalent, at rates from 40%-50%.
Millie Kwan, MD, PhD, an allergy specialist at University of North Carolina in Chapel Hill, said in an interview that in the U.S. there’s been a culture change in the direction of antibiotic restraint – but there are still problems.
“It’s a lot easier for us to whip out our prescription pads and prescribe antibiotics for an asthma patient who’s having a flare-up or a patient who has atopic dermatitis before addressing the underlying mechanism directly,” Dr. Kwan said. She agreed that antibiotic overuse is prevalent in pregnancies in the U.S., and she said that starts with the high prevalence of cesarean births. Nearly one-third of all births in the U.S. are by C-section, twice the rate recommended by the World Health Organization.
“Just bypassing the birth canal actually changes what kind of microflora the infant is being exposed to,” Dr. Kwan said. “That’s the first huge problem.”
The second problem, she said, is the potential for overuse of antibiotics with the surgical procedure.
The researchers wrote that pre-, pro- or postbiotics might alter the course of allergic disease, but clear evidence is lacking.
Until now, Dr. Tramper-Stranders said, pre- or probiotic treatment in infancy, irrespective of previous antibiotic use, has not proved effective in preventing allergies.
Data describing the effect of pre- or probiotics after an antibiotic course are scarce, are limited to older children and adults, and are focused on short-term effects, such as diarrhea prevention, she explained.
Dr. Kwan says she agrees that current data are not strong enough to recommend one over another.
“We don’t even know what the normal amount of bacteria should be to constitute an environment where the immune system develops ‘normally,’ “ she said.
Antibiotics should be prescribed cautiously and by following current recommendations to use the narrowest spectrum available, the authors wrote. Future research in antibiotic stewardship should incorporate biomarker-guided therapy to determine which patients might benefit most from antibiotic therapy.
“Practicing antibiotic stewardship needs recurrent attention and we hope that with this initiative, we specifically reach allergy doctors who will rethink their next [antibiotic] prescription. Within our EAACI task force, we will next work on a guideline for rational antibiotic use in asthma,” Dr. Tramper-Stranders said.
The review’s authors and Dr. Kwan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Urgent recommendations from a European Academy of Allergy and Clinical Immunology (EAACI) task force are aimed at reducing antibiotic overuse with allergic disease.
Top recommendations include limiting antibiotic therapy in pregnancy and early childhood to help reduce the allergy epidemic in children, and restricting antibiotic therapy in exacerbations and chronic treatment of allergic diseases, especially asthma and atopic dermatitis.
The review, by lead author Gerdien Tramper-Stranders, MD, PhD, department of pediatrics, Franciscus Gasthuis & Vlietland Hospital, Rotterdam, the Netherlands, and colleagues, was published online Aug. 13 in the journal Allergy.
Several studies have shown that use of antibiotics in childhood and during pregnancy is associated with disturbing the intestinal and respiratory microbiome, which in turn leads to dysbiosis and an increased risk of acquiring allergic diseases, the authors noted.
In addition, patients with allergic diseases such as asthma have a higher risk of being prescribed antibiotics for infections compared with the general population, despite lack of clear clinical benefit.
“In fact, there are no clear data supporting antibiotic prescriptions for acute exacerbations; and clinical and/or laboratory criteria are lacking,” the authors wrote.
Despite that lack of data, antibiotics are often prescribed for exacerbations along with oral corticosteroids, Dr. Tramper-Stranders said in an interview. Some patients may benefit from antibiotics in a flare-up, she said, but more research is needed to determine which ones.
Dr. Tramper-Stranders said Franciscus has begun a large study that includes patients with asthma exacerbations to find biomarkers that might predict the type or origin of exacerbation to personalize treatment.
Recommendations have global relevance
She said although the recommendations are coming from the EAACI group, they apply worldwide.
“Especially in countries outside Northern Europe, antibiotic use is tremendous, leading to high rates of antibiotic resistance; but also increasing the risk for developing allergic diseases when prescribed in infancy,” she said.
She pointed out that in the United States, as many as one in six children receive unnecessary antibiotics for an asthma exacerbation. Overtreatment in adults with flare-ups is also prevalent, at rates from 40%-50%.
Millie Kwan, MD, PhD, an allergy specialist at University of North Carolina in Chapel Hill, said in an interview that in the U.S. there’s been a culture change in the direction of antibiotic restraint – but there are still problems.
“It’s a lot easier for us to whip out our prescription pads and prescribe antibiotics for an asthma patient who’s having a flare-up or a patient who has atopic dermatitis before addressing the underlying mechanism directly,” Dr. Kwan said. She agreed that antibiotic overuse is prevalent in pregnancies in the U.S., and she said that starts with the high prevalence of cesarean births. Nearly one-third of all births in the U.S. are by C-section, twice the rate recommended by the World Health Organization.
“Just bypassing the birth canal actually changes what kind of microflora the infant is being exposed to,” Dr. Kwan said. “That’s the first huge problem.”
The second problem, she said, is the potential for overuse of antibiotics with the surgical procedure.
The researchers wrote that pre-, pro- or postbiotics might alter the course of allergic disease, but clear evidence is lacking.
Until now, Dr. Tramper-Stranders said, pre- or probiotic treatment in infancy, irrespective of previous antibiotic use, has not proved effective in preventing allergies.
Data describing the effect of pre- or probiotics after an antibiotic course are scarce, are limited to older children and adults, and are focused on short-term effects, such as diarrhea prevention, she explained.
Dr. Kwan says she agrees that current data are not strong enough to recommend one over another.
“We don’t even know what the normal amount of bacteria should be to constitute an environment where the immune system develops ‘normally,’ “ she said.
Antibiotics should be prescribed cautiously and by following current recommendations to use the narrowest spectrum available, the authors wrote. Future research in antibiotic stewardship should incorporate biomarker-guided therapy to determine which patients might benefit most from antibiotic therapy.
“Practicing antibiotic stewardship needs recurrent attention and we hope that with this initiative, we specifically reach allergy doctors who will rethink their next [antibiotic] prescription. Within our EAACI task force, we will next work on a guideline for rational antibiotic use in asthma,” Dr. Tramper-Stranders said.
The review’s authors and Dr. Kwan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
TB prevention in people with HIV: How short can we go?
A 3-month, 12-dose regimen of rifapentine and isoniazid (INH) was less toxic, had better compliance, and showed similar efficacy as 6 months of INH alone in preventing tuberculosis (TB) in people with HIV, according to the results of a clinical trial reported in Annals of Internal Medicine.
The study, a randomized pragmatic trial in South Africa, Ethiopia, and Mozambique, was called WHIP3TB (Weekly High Dose Isoniazid and Rifapentine [P] Periodic Prophylaxis for TB).
Investigators randomized patients to three groups, comparing a 3-month course of weekly rifapentine-INH, given either once or repeated in a year, with daily isoniazid for 6 months. At 1 year, 90% of the rifapentine-INH group (3HP) were still on therapy, compared with only 50.5% in the INH group.
In the study, patients were initially assessed for TB using the World Health Organization four-symptom screen, but the sensitivity in HIV patients on antiretrovirals (ARVs) was only 53%. In addition to symptoms, screening at 12 months included a chest x-ray and sputum culture.
Of the 30 patients at month 12 with confirmed TB, 26 were asymptomatic, suggesting physicians should do further evaluation prior to initiating preventive TB treatment (which was not part of the WHO recommendation when the study was initiated).
Another unexpected finding was that 10.2% of the TB cases detected in the combined 3HP groups in South Africa, along with 18% of the cases in Mozambique, had rifampin resistance.
Investigator Gavin Churchyard, MBBCh, PhD, CEO of the Aurum Institute in Johannesburg, South Africa, said in an interview: “It appeared that taking this potent short course regimen – they’re just taking a single course – provided the same level of protection as taking repeat courses of the antibiotics. So that’s good news.” He noted, too, that TB transmission rates have been declining in sub-Saharan Africa because of ARV, and “so it may just be that a single course is now adequate because the risk of exposure and reinfection” is decreasing.
But Madhu Pai, MD, PhD, associate director, McGill International TB Centre, Montreal, who was not involved in the study, shared a more cautious interpretation. He said in an interview that the 2020 WHO Consolidated Guidelines on Tuberculosis state: “In settings with high TB transmission, adults and adolescents living with HIV ... should receive at least 36 months of daily isoniazid preventive therapy (IPT) ... whether or not the person is on ART.” The problem is that almost no one can tolerate prolonged therapy with INH because of side effects, as has been shown in numerous studies.
For successful TB treatment, Dr. Pai said, “Even 3HP is not going to cut it; they’re going to get reinfected again. So that shortening of that 36 months is what this trial is really all about, in terms of new information ... and they were not successful.” But because this is still the most practical course, Dr. Pai suggests that follow-up monitoring for reinfection will be the most likely path forward.
Dr. Churchyard concluded: “If we wanted to end the global TB epidemic, we need to continue to find ways to further reduce the risk of TB overall at a population level, and then amongst high-risk groups such as people with HIV, including those on ARVs, and who have had a course of preventive therapy. ... We need to look for other strategies to further reduce that risk. Part of those strategies may be doing a more intensive screen. But also, it may be adding another intervention, particularly TB vaccines. ... No single intervention by itself will adequately address the risk of TB in people with HIV in these high TB transmission settings.”
Dr. Pai reported no relevant financial relationships. Dr. Churchyard has reported participation in a Sanofi advisory committee on the prevention of TB. Judy Stone, MD, is an infectious disease specialist and author of “Resilience: One Family’s Story of Hope and Triumph Over Evil” and of “Conducting Clinical Research.”
A version of this article first appeared on Medscape.com.
A 3-month, 12-dose regimen of rifapentine and isoniazid (INH) was less toxic, had better compliance, and showed similar efficacy as 6 months of INH alone in preventing tuberculosis (TB) in people with HIV, according to the results of a clinical trial reported in Annals of Internal Medicine.
The study, a randomized pragmatic trial in South Africa, Ethiopia, and Mozambique, was called WHIP3TB (Weekly High Dose Isoniazid and Rifapentine [P] Periodic Prophylaxis for TB).
Investigators randomized patients to three groups, comparing a 3-month course of weekly rifapentine-INH, given either once or repeated in a year, with daily isoniazid for 6 months. At 1 year, 90% of the rifapentine-INH group (3HP) were still on therapy, compared with only 50.5% in the INH group.
In the study, patients were initially assessed for TB using the World Health Organization four-symptom screen, but the sensitivity in HIV patients on antiretrovirals (ARVs) was only 53%. In addition to symptoms, screening at 12 months included a chest x-ray and sputum culture.
Of the 30 patients at month 12 with confirmed TB, 26 were asymptomatic, suggesting physicians should do further evaluation prior to initiating preventive TB treatment (which was not part of the WHO recommendation when the study was initiated).
Another unexpected finding was that 10.2% of the TB cases detected in the combined 3HP groups in South Africa, along with 18% of the cases in Mozambique, had rifampin resistance.
Investigator Gavin Churchyard, MBBCh, PhD, CEO of the Aurum Institute in Johannesburg, South Africa, said in an interview: “It appeared that taking this potent short course regimen – they’re just taking a single course – provided the same level of protection as taking repeat courses of the antibiotics. So that’s good news.” He noted, too, that TB transmission rates have been declining in sub-Saharan Africa because of ARV, and “so it may just be that a single course is now adequate because the risk of exposure and reinfection” is decreasing.
But Madhu Pai, MD, PhD, associate director, McGill International TB Centre, Montreal, who was not involved in the study, shared a more cautious interpretation. He said in an interview that the 2020 WHO Consolidated Guidelines on Tuberculosis state: “In settings with high TB transmission, adults and adolescents living with HIV ... should receive at least 36 months of daily isoniazid preventive therapy (IPT) ... whether or not the person is on ART.” The problem is that almost no one can tolerate prolonged therapy with INH because of side effects, as has been shown in numerous studies.
For successful TB treatment, Dr. Pai said, “Even 3HP is not going to cut it; they’re going to get reinfected again. So that shortening of that 36 months is what this trial is really all about, in terms of new information ... and they were not successful.” But because this is still the most practical course, Dr. Pai suggests that follow-up monitoring for reinfection will be the most likely path forward.
Dr. Churchyard concluded: “If we wanted to end the global TB epidemic, we need to continue to find ways to further reduce the risk of TB overall at a population level, and then amongst high-risk groups such as people with HIV, including those on ARVs, and who have had a course of preventive therapy. ... We need to look for other strategies to further reduce that risk. Part of those strategies may be doing a more intensive screen. But also, it may be adding another intervention, particularly TB vaccines. ... No single intervention by itself will adequately address the risk of TB in people with HIV in these high TB transmission settings.”
Dr. Pai reported no relevant financial relationships. Dr. Churchyard has reported participation in a Sanofi advisory committee on the prevention of TB. Judy Stone, MD, is an infectious disease specialist and author of “Resilience: One Family’s Story of Hope and Triumph Over Evil” and of “Conducting Clinical Research.”
A version of this article first appeared on Medscape.com.
A 3-month, 12-dose regimen of rifapentine and isoniazid (INH) was less toxic, had better compliance, and showed similar efficacy as 6 months of INH alone in preventing tuberculosis (TB) in people with HIV, according to the results of a clinical trial reported in Annals of Internal Medicine.
The study, a randomized pragmatic trial in South Africa, Ethiopia, and Mozambique, was called WHIP3TB (Weekly High Dose Isoniazid and Rifapentine [P] Periodic Prophylaxis for TB).
Investigators randomized patients to three groups, comparing a 3-month course of weekly rifapentine-INH, given either once or repeated in a year, with daily isoniazid for 6 months. At 1 year, 90% of the rifapentine-INH group (3HP) were still on therapy, compared with only 50.5% in the INH group.
In the study, patients were initially assessed for TB using the World Health Organization four-symptom screen, but the sensitivity in HIV patients on antiretrovirals (ARVs) was only 53%. In addition to symptoms, screening at 12 months included a chest x-ray and sputum culture.
Of the 30 patients at month 12 with confirmed TB, 26 were asymptomatic, suggesting physicians should do further evaluation prior to initiating preventive TB treatment (which was not part of the WHO recommendation when the study was initiated).
Another unexpected finding was that 10.2% of the TB cases detected in the combined 3HP groups in South Africa, along with 18% of the cases in Mozambique, had rifampin resistance.
Investigator Gavin Churchyard, MBBCh, PhD, CEO of the Aurum Institute in Johannesburg, South Africa, said in an interview: “It appeared that taking this potent short course regimen – they’re just taking a single course – provided the same level of protection as taking repeat courses of the antibiotics. So that’s good news.” He noted, too, that TB transmission rates have been declining in sub-Saharan Africa because of ARV, and “so it may just be that a single course is now adequate because the risk of exposure and reinfection” is decreasing.
But Madhu Pai, MD, PhD, associate director, McGill International TB Centre, Montreal, who was not involved in the study, shared a more cautious interpretation. He said in an interview that the 2020 WHO Consolidated Guidelines on Tuberculosis state: “In settings with high TB transmission, adults and adolescents living with HIV ... should receive at least 36 months of daily isoniazid preventive therapy (IPT) ... whether or not the person is on ART.” The problem is that almost no one can tolerate prolonged therapy with INH because of side effects, as has been shown in numerous studies.
For successful TB treatment, Dr. Pai said, “Even 3HP is not going to cut it; they’re going to get reinfected again. So that shortening of that 36 months is what this trial is really all about, in terms of new information ... and they were not successful.” But because this is still the most practical course, Dr. Pai suggests that follow-up monitoring for reinfection will be the most likely path forward.
Dr. Churchyard concluded: “If we wanted to end the global TB epidemic, we need to continue to find ways to further reduce the risk of TB overall at a population level, and then amongst high-risk groups such as people with HIV, including those on ARVs, and who have had a course of preventive therapy. ... We need to look for other strategies to further reduce that risk. Part of those strategies may be doing a more intensive screen. But also, it may be adding another intervention, particularly TB vaccines. ... No single intervention by itself will adequately address the risk of TB in people with HIV in these high TB transmission settings.”
Dr. Pai reported no relevant financial relationships. Dr. Churchyard has reported participation in a Sanofi advisory committee on the prevention of TB. Judy Stone, MD, is an infectious disease specialist and author of “Resilience: One Family’s Story of Hope and Triumph Over Evil” and of “Conducting Clinical Research.”
A version of this article first appeared on Medscape.com.
FDA warns clinicians to stop using Eco-Med products because of contamination concerns
Earlier this month, the Centers for Disease Control and Prevention and the FDA announced an outbreak of at least 15 Bcc infections associated with contaminated ultrasound gel, and, according to the FDA, Eco-Med ultrasound gels have now been linked to at least 59 infections, 48 of which were blood infections.
On Aug. 4, the Canadian pharmaceutical company, based in Etobicoke, Ont., initiated a voluntary recall of certain lots of EcoGel 200 Ultrasound gel because of contamination with Bcc, but now the FDA warns that all Eco-Med’s ultrasound gels and lotions are at risk.
“The FDA’s determination is based on concerns that the company did not complete its investigation of the issues, the root cause and extent of bacterial contamination was not identified, and multiple products could be affected by manufacturing issues associated with the company’s ultrasound gel (such as inappropriate testing of finished product, inadequate testing of raw materials, and a lack of environmental controls),” the FDA said in a letter to health care providers published Aug. 18.
The letter lists 25 products manufactured by Eco-Med that are sold by distributors in 10 different countries, including the United States and Canada. The list may not be completely comprehensive, the organization notes.
Eco-Med has ceased all operations and is no longer manufacturing or distributing products, according to the FDA statement. Both phone numbers listed for the company were not in operation at the time of reporting.
Beyond stopping use of and discarding Eco-Med products, the FDA recommends that health care providers and facilities stop purchases of Eco-Med products, contact distributors with product disposal questions, and follow professional society guidelines and CDC guidelines for ultrasound use and cleaning products. Providers are encouraged to report adverse events related to Eco-Med ultrasound gels or lotions through MedWatch: The FDA Safety Information and Adverse Event Reporting program.
Though Eco-Med is listed as one of the “prominent players in the ultrasound gel market,” according to a June 2020 report by Grand View Research, the announcement will likely not cause many issues, Lauren Golding, MD, chair of the American College of Radiology Commission on Ultrasound, said in an interview.
“Fortunately, several companies produce ultrasound gel. Barring unforeseen circumstances, we do not expect this FDA action to have a widespread impact on patients’ access to ultrasound exams in the United States,” she said.
A version of this article first appeared on Medscape.com.
Earlier this month, the Centers for Disease Control and Prevention and the FDA announced an outbreak of at least 15 Bcc infections associated with contaminated ultrasound gel, and, according to the FDA, Eco-Med ultrasound gels have now been linked to at least 59 infections, 48 of which were blood infections.
On Aug. 4, the Canadian pharmaceutical company, based in Etobicoke, Ont., initiated a voluntary recall of certain lots of EcoGel 200 Ultrasound gel because of contamination with Bcc, but now the FDA warns that all Eco-Med’s ultrasound gels and lotions are at risk.
“The FDA’s determination is based on concerns that the company did not complete its investigation of the issues, the root cause and extent of bacterial contamination was not identified, and multiple products could be affected by manufacturing issues associated with the company’s ultrasound gel (such as inappropriate testing of finished product, inadequate testing of raw materials, and a lack of environmental controls),” the FDA said in a letter to health care providers published Aug. 18.
The letter lists 25 products manufactured by Eco-Med that are sold by distributors in 10 different countries, including the United States and Canada. The list may not be completely comprehensive, the organization notes.
Eco-Med has ceased all operations and is no longer manufacturing or distributing products, according to the FDA statement. Both phone numbers listed for the company were not in operation at the time of reporting.
Beyond stopping use of and discarding Eco-Med products, the FDA recommends that health care providers and facilities stop purchases of Eco-Med products, contact distributors with product disposal questions, and follow professional society guidelines and CDC guidelines for ultrasound use and cleaning products. Providers are encouraged to report adverse events related to Eco-Med ultrasound gels or lotions through MedWatch: The FDA Safety Information and Adverse Event Reporting program.
Though Eco-Med is listed as one of the “prominent players in the ultrasound gel market,” according to a June 2020 report by Grand View Research, the announcement will likely not cause many issues, Lauren Golding, MD, chair of the American College of Radiology Commission on Ultrasound, said in an interview.
“Fortunately, several companies produce ultrasound gel. Barring unforeseen circumstances, we do not expect this FDA action to have a widespread impact on patients’ access to ultrasound exams in the United States,” she said.
A version of this article first appeared on Medscape.com.
Earlier this month, the Centers for Disease Control and Prevention and the FDA announced an outbreak of at least 15 Bcc infections associated with contaminated ultrasound gel, and, according to the FDA, Eco-Med ultrasound gels have now been linked to at least 59 infections, 48 of which were blood infections.
On Aug. 4, the Canadian pharmaceutical company, based in Etobicoke, Ont., initiated a voluntary recall of certain lots of EcoGel 200 Ultrasound gel because of contamination with Bcc, but now the FDA warns that all Eco-Med’s ultrasound gels and lotions are at risk.
“The FDA’s determination is based on concerns that the company did not complete its investigation of the issues, the root cause and extent of bacterial contamination was not identified, and multiple products could be affected by manufacturing issues associated with the company’s ultrasound gel (such as inappropriate testing of finished product, inadequate testing of raw materials, and a lack of environmental controls),” the FDA said in a letter to health care providers published Aug. 18.
The letter lists 25 products manufactured by Eco-Med that are sold by distributors in 10 different countries, including the United States and Canada. The list may not be completely comprehensive, the organization notes.
Eco-Med has ceased all operations and is no longer manufacturing or distributing products, according to the FDA statement. Both phone numbers listed for the company were not in operation at the time of reporting.
Beyond stopping use of and discarding Eco-Med products, the FDA recommends that health care providers and facilities stop purchases of Eco-Med products, contact distributors with product disposal questions, and follow professional society guidelines and CDC guidelines for ultrasound use and cleaning products. Providers are encouraged to report adverse events related to Eco-Med ultrasound gels or lotions through MedWatch: The FDA Safety Information and Adverse Event Reporting program.
Though Eco-Med is listed as one of the “prominent players in the ultrasound gel market,” according to a June 2020 report by Grand View Research, the announcement will likely not cause many issues, Lauren Golding, MD, chair of the American College of Radiology Commission on Ultrasound, said in an interview.
“Fortunately, several companies produce ultrasound gel. Barring unforeseen circumstances, we do not expect this FDA action to have a widespread impact on patients’ access to ultrasound exams in the United States,” she said.
A version of this article first appeared on Medscape.com.
Dostarlimab indication broadened to all dMMR solid tumors
The agency approved the drug in April for dMMR recurrent or advanced endometrial cancer that has progressed during or following treatment with a platinum-containing regimen. The labeling notes that dMMR status for both indications must be determined through an FDA-approved test.
The accelerated approval “may be contingent upon verification and description of clinical benefit in a confirmatory” trial, the labeling says.
The new indication was based results from 209 patients in the GARNET trial. In that trial, the objective response rate was 41.6% across dMMR endometrial and other solid tumors. The complete response rate was 9.1%.
The median duration of response was 34.7 months. For 95% of patients who responded to treatment, the duration of response was 6 months or longer, according to a press release from the maker, GlaxoSmithKline.
In mismatch repair deficiency, tumors contain abnormalities that affect the proper repair of DNA. Prevalence in the United States is estimated to be 14%. The deficiency is particularly common in endometrial, colorectal, and other gastrointestinal cancers, the company said.
The drug was administered in GARNET as a 500-mg intravenous infusion every 3 weeks in four doses, followed by 1,000 mg once every 6 weeks until disease progression or unacceptable toxicity.
Common adverse events included fatigue/asthenia (42%), anemia (30%), diarrhea (25%), and nausea (22%). The most common grade 3 or 4 adverse reactions included anemia, fatigue/asthenia, increased transaminases, sepsis, and acute kidney injury.
As with other PD-1/PD-L1 blockers, there’s also a possibility of severe and fatal immune-mediated adverse reactions in any organ system either during or after treatment, including immune-mediated pneumonitis, colitis, and hepatitis.
GlaxoSmithKline said it’s studying dostarlimab in earlier lines of treatment for endometrial cancer and in combination with other agents for other advanced/metastatic cancers.
A version of this article first appeared on Medscape.com.
The agency approved the drug in April for dMMR recurrent or advanced endometrial cancer that has progressed during or following treatment with a platinum-containing regimen. The labeling notes that dMMR status for both indications must be determined through an FDA-approved test.
The accelerated approval “may be contingent upon verification and description of clinical benefit in a confirmatory” trial, the labeling says.
The new indication was based results from 209 patients in the GARNET trial. In that trial, the objective response rate was 41.6% across dMMR endometrial and other solid tumors. The complete response rate was 9.1%.
The median duration of response was 34.7 months. For 95% of patients who responded to treatment, the duration of response was 6 months or longer, according to a press release from the maker, GlaxoSmithKline.
In mismatch repair deficiency, tumors contain abnormalities that affect the proper repair of DNA. Prevalence in the United States is estimated to be 14%. The deficiency is particularly common in endometrial, colorectal, and other gastrointestinal cancers, the company said.
The drug was administered in GARNET as a 500-mg intravenous infusion every 3 weeks in four doses, followed by 1,000 mg once every 6 weeks until disease progression or unacceptable toxicity.
Common adverse events included fatigue/asthenia (42%), anemia (30%), diarrhea (25%), and nausea (22%). The most common grade 3 or 4 adverse reactions included anemia, fatigue/asthenia, increased transaminases, sepsis, and acute kidney injury.
As with other PD-1/PD-L1 blockers, there’s also a possibility of severe and fatal immune-mediated adverse reactions in any organ system either during or after treatment, including immune-mediated pneumonitis, colitis, and hepatitis.
GlaxoSmithKline said it’s studying dostarlimab in earlier lines of treatment for endometrial cancer and in combination with other agents for other advanced/metastatic cancers.
A version of this article first appeared on Medscape.com.
The agency approved the drug in April for dMMR recurrent or advanced endometrial cancer that has progressed during or following treatment with a platinum-containing regimen. The labeling notes that dMMR status for both indications must be determined through an FDA-approved test.
The accelerated approval “may be contingent upon verification and description of clinical benefit in a confirmatory” trial, the labeling says.
The new indication was based results from 209 patients in the GARNET trial. In that trial, the objective response rate was 41.6% across dMMR endometrial and other solid tumors. The complete response rate was 9.1%.
The median duration of response was 34.7 months. For 95% of patients who responded to treatment, the duration of response was 6 months or longer, according to a press release from the maker, GlaxoSmithKline.
In mismatch repair deficiency, tumors contain abnormalities that affect the proper repair of DNA. Prevalence in the United States is estimated to be 14%. The deficiency is particularly common in endometrial, colorectal, and other gastrointestinal cancers, the company said.
The drug was administered in GARNET as a 500-mg intravenous infusion every 3 weeks in four doses, followed by 1,000 mg once every 6 weeks until disease progression or unacceptable toxicity.
Common adverse events included fatigue/asthenia (42%), anemia (30%), diarrhea (25%), and nausea (22%). The most common grade 3 or 4 adverse reactions included anemia, fatigue/asthenia, increased transaminases, sepsis, and acute kidney injury.
As with other PD-1/PD-L1 blockers, there’s also a possibility of severe and fatal immune-mediated adverse reactions in any organ system either during or after treatment, including immune-mediated pneumonitis, colitis, and hepatitis.
GlaxoSmithKline said it’s studying dostarlimab in earlier lines of treatment for endometrial cancer and in combination with other agents for other advanced/metastatic cancers.
A version of this article first appeared on Medscape.com.
FDA OKs belzutifan for cancers tied to von Hippel–Lindau disease
Belzutifan is a selective small-molecule inhibitor of hypoxia-inducible factor and a first-in-class drug.
The new approval is based on safety and efficacy results from the ongoing Study 004, an open-label clinical trial involving 61 patients with VHL-associated RCC with at least one measurable solid tumor localized to the kidney. Enrolled patients had other VHL-associated tumors, including CNS hemangioblastomas and pNETs.
Patients received belzutifan 120 mg once daily until disease progression or unacceptable toxicity.
The overall response rate, which was the study’s primary endpoint, was 49% in patients with VHL-associated RCC. Additional efficacy endpoints included duration of response (DoR), which was not reached. So far, 56% of responders had DoR of at least 12 months. The median time to response was 8 months.
Among the patients in the study with other VHL-associated non-RCC tumors, 24 patients with CNS hemangioblastomas had an ORR of 63%, and 12 patients with pNETs had an ORR of 83%. Median DoR was not reached,with 73% and 50% of patients having response durations of at least 12 months for CNS hemangioblastomas and pNET, respectively.
The most common adverse reactions (≥20% of patients), according to the FDA, were decreased hemoglobin, anemia, fatigue, increased creatinine, headache, dizziness, increased glucose, and nausea.
Notably, anemia and hypoxia from belzutifan use can be severe. In Study 004, anemia occurred in 90% of patients and 7% had grade 3 anemia. Patients should be transfused as clinically indicated. Erythropoiesis-stimulating agents for anemia are not recommended in patients treated with belzutifan. In Study 004, hypoxia occurred in 1.6% of patients.
Belzutifan can render some hormonal contraceptives ineffective, and belzutifan exposure during pregnancy can cause embryo-fetal harm; see full prescribing information for Welireg.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence, and used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application. The application was granted priority review by the FDA.
A version of this article first appeared on Medscape.com.
Belzutifan is a selective small-molecule inhibitor of hypoxia-inducible factor and a first-in-class drug.
The new approval is based on safety and efficacy results from the ongoing Study 004, an open-label clinical trial involving 61 patients with VHL-associated RCC with at least one measurable solid tumor localized to the kidney. Enrolled patients had other VHL-associated tumors, including CNS hemangioblastomas and pNETs.
Patients received belzutifan 120 mg once daily until disease progression or unacceptable toxicity.
The overall response rate, which was the study’s primary endpoint, was 49% in patients with VHL-associated RCC. Additional efficacy endpoints included duration of response (DoR), which was not reached. So far, 56% of responders had DoR of at least 12 months. The median time to response was 8 months.
Among the patients in the study with other VHL-associated non-RCC tumors, 24 patients with CNS hemangioblastomas had an ORR of 63%, and 12 patients with pNETs had an ORR of 83%. Median DoR was not reached,with 73% and 50% of patients having response durations of at least 12 months for CNS hemangioblastomas and pNET, respectively.
The most common adverse reactions (≥20% of patients), according to the FDA, were decreased hemoglobin, anemia, fatigue, increased creatinine, headache, dizziness, increased glucose, and nausea.
Notably, anemia and hypoxia from belzutifan use can be severe. In Study 004, anemia occurred in 90% of patients and 7% had grade 3 anemia. Patients should be transfused as clinically indicated. Erythropoiesis-stimulating agents for anemia are not recommended in patients treated with belzutifan. In Study 004, hypoxia occurred in 1.6% of patients.
Belzutifan can render some hormonal contraceptives ineffective, and belzutifan exposure during pregnancy can cause embryo-fetal harm; see full prescribing information for Welireg.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence, and used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application. The application was granted priority review by the FDA.
A version of this article first appeared on Medscape.com.
Belzutifan is a selective small-molecule inhibitor of hypoxia-inducible factor and a first-in-class drug.
The new approval is based on safety and efficacy results from the ongoing Study 004, an open-label clinical trial involving 61 patients with VHL-associated RCC with at least one measurable solid tumor localized to the kidney. Enrolled patients had other VHL-associated tumors, including CNS hemangioblastomas and pNETs.
Patients received belzutifan 120 mg once daily until disease progression or unacceptable toxicity.
The overall response rate, which was the study’s primary endpoint, was 49% in patients with VHL-associated RCC. Additional efficacy endpoints included duration of response (DoR), which was not reached. So far, 56% of responders had DoR of at least 12 months. The median time to response was 8 months.
Among the patients in the study with other VHL-associated non-RCC tumors, 24 patients with CNS hemangioblastomas had an ORR of 63%, and 12 patients with pNETs had an ORR of 83%. Median DoR was not reached,with 73% and 50% of patients having response durations of at least 12 months for CNS hemangioblastomas and pNET, respectively.
The most common adverse reactions (≥20% of patients), according to the FDA, were decreased hemoglobin, anemia, fatigue, increased creatinine, headache, dizziness, increased glucose, and nausea.
Notably, anemia and hypoxia from belzutifan use can be severe. In Study 004, anemia occurred in 90% of patients and 7% had grade 3 anemia. Patients should be transfused as clinically indicated. Erythropoiesis-stimulating agents for anemia are not recommended in patients treated with belzutifan. In Study 004, hypoxia occurred in 1.6% of patients.
Belzutifan can render some hormonal contraceptives ineffective, and belzutifan exposure during pregnancy can cause embryo-fetal harm; see full prescribing information for Welireg.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence, and used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application. The application was granted priority review by the FDA.
A version of this article first appeared on Medscape.com.
Stop blaming the unvaccinated
As politicians battle over masks and mandates, heated rhetoric has been used to describe the fourth heartbreaking surge in COVID as a “pandemic of the unvaccinated.”
While it may serve to further divide red and blue states, I disagree with the assertion that the current surge in cases is driven simply by the unvaccinated. Why? First, the premise would assume complete efficacy with our vaccinated population, which is statistically incorrect (at least 15 million of the U.S. population never completed a second round of injections), which means they were not considered “fully vaccinated.”
Alternately, we need to examine what has occurred in nations with significantly higher vaccination rates than ours (the United Kingdom and Israel) to realize that variants have overrun the dramatic success achieved in those countries as well. Israel, once considered to be the most vaccinated country in the world, is facing a brutal fourth wave of COVID that has sent the country spiraling into another heartbreaking lockdown.
The unvaccinated could hardly be blamed for what is happening in either of these highly vaccinated countries.
The concept of blame
So why use blame? It defeats the purpose of encouraging those who are hesitant or possibly misinformed or disenfranchised to move forward. It lacks compassion. It does not encompass the art and science of nursing (for example, the University of Southern Indiana), such as those that hospitals have used to frame optimal nursing care. I abhor the idea of labeling because it denies the prospect of future comprehension.
Labeling reminds me of one of the saddest cases in my career.
An unfortunate case
I was the nurse caring for a man from a motor vehicular accident where an entire family was brutally killed. My patient was alleged to be the cause, with a blood alcohol level of 0.40%+ post hydration, intubated and ventilated, with a flailed chest and multiple orthopedic injuries as well as blunt head trauma. He was secured to the bed with handcuffs, although that was unnecessary. Multiple times I was asked how I could possibly care for such an individual, by the police and even a few colleagues. But it was not my place to judge the man.
He was in pain, and he was dying. I comforted him for the 2 weeks it took his battered body to pass into the next realm. No one visited him except the police, eagerly waiting for the man to wake up to explain the tragic events that occurred. It was my job to ease what pain I could and protect him from labels. Did he deserve the labels? Who knew? I did not care. I cared about his writhing and his physical anguish.
The comparison
Blame did not help the situation then, nor does it help us move forward now. As nurses, we seek to work within a framework of understanding. As we tire of caring for thousands of COVID patients, we do not stop to ask if they “deserve” care or if they have taken precautions and lived reasonably prior to seeking assistance for disease. We would not be nurses if we did this.
Think about Gov. Greg Abbott, who has asked that Texans not be allowed to mandate masks for children returning to school. He has recently been diagnosed with COVID, despite assuring the public he is fully vaccinated. Politically, his diagnosis could be visualized as a fiasco for a purple state where he has been adamant in denying the efficacy of masks for children.
Yet, his diagnosis should not be fodder for the press. The first concern should be his health and well-being, similar for any man of his age and potential comorbidity.
Conclusion
We should be people first, human beings that remain interconnected by our need for care and survival, not conservatives, independents, or liberals, not “vaccinated or unvaccinated,” not seen as “breakthrough” infections, or the immunosuppressed possibly unable to mount a robust response to COVID.
Labels do not define the ability to effectively defeat coronavirus or variants, as highly vaccinated countries have demonstrated in recent months. We are in the midst of a global pandemic, and the battle is raging onward.
In fact, the longer this pandemic continues, the more likely it is we will need to live with this as an endemic disease, so we should stop blaming those who become ill and need support.
It could be any of us.
A version of this article first appeared on Medscape.com.
As politicians battle over masks and mandates, heated rhetoric has been used to describe the fourth heartbreaking surge in COVID as a “pandemic of the unvaccinated.”
While it may serve to further divide red and blue states, I disagree with the assertion that the current surge in cases is driven simply by the unvaccinated. Why? First, the premise would assume complete efficacy with our vaccinated population, which is statistically incorrect (at least 15 million of the U.S. population never completed a second round of injections), which means they were not considered “fully vaccinated.”
Alternately, we need to examine what has occurred in nations with significantly higher vaccination rates than ours (the United Kingdom and Israel) to realize that variants have overrun the dramatic success achieved in those countries as well. Israel, once considered to be the most vaccinated country in the world, is facing a brutal fourth wave of COVID that has sent the country spiraling into another heartbreaking lockdown.
The unvaccinated could hardly be blamed for what is happening in either of these highly vaccinated countries.
The concept of blame
So why use blame? It defeats the purpose of encouraging those who are hesitant or possibly misinformed or disenfranchised to move forward. It lacks compassion. It does not encompass the art and science of nursing (for example, the University of Southern Indiana), such as those that hospitals have used to frame optimal nursing care. I abhor the idea of labeling because it denies the prospect of future comprehension.
Labeling reminds me of one of the saddest cases in my career.
An unfortunate case
I was the nurse caring for a man from a motor vehicular accident where an entire family was brutally killed. My patient was alleged to be the cause, with a blood alcohol level of 0.40%+ post hydration, intubated and ventilated, with a flailed chest and multiple orthopedic injuries as well as blunt head trauma. He was secured to the bed with handcuffs, although that was unnecessary. Multiple times I was asked how I could possibly care for such an individual, by the police and even a few colleagues. But it was not my place to judge the man.
He was in pain, and he was dying. I comforted him for the 2 weeks it took his battered body to pass into the next realm. No one visited him except the police, eagerly waiting for the man to wake up to explain the tragic events that occurred. It was my job to ease what pain I could and protect him from labels. Did he deserve the labels? Who knew? I did not care. I cared about his writhing and his physical anguish.
The comparison
Blame did not help the situation then, nor does it help us move forward now. As nurses, we seek to work within a framework of understanding. As we tire of caring for thousands of COVID patients, we do not stop to ask if they “deserve” care or if they have taken precautions and lived reasonably prior to seeking assistance for disease. We would not be nurses if we did this.
Think about Gov. Greg Abbott, who has asked that Texans not be allowed to mandate masks for children returning to school. He has recently been diagnosed with COVID, despite assuring the public he is fully vaccinated. Politically, his diagnosis could be visualized as a fiasco for a purple state where he has been adamant in denying the efficacy of masks for children.
Yet, his diagnosis should not be fodder for the press. The first concern should be his health and well-being, similar for any man of his age and potential comorbidity.
Conclusion
We should be people first, human beings that remain interconnected by our need for care and survival, not conservatives, independents, or liberals, not “vaccinated or unvaccinated,” not seen as “breakthrough” infections, or the immunosuppressed possibly unable to mount a robust response to COVID.
Labels do not define the ability to effectively defeat coronavirus or variants, as highly vaccinated countries have demonstrated in recent months. We are in the midst of a global pandemic, and the battle is raging onward.
In fact, the longer this pandemic continues, the more likely it is we will need to live with this as an endemic disease, so we should stop blaming those who become ill and need support.
It could be any of us.
A version of this article first appeared on Medscape.com.
As politicians battle over masks and mandates, heated rhetoric has been used to describe the fourth heartbreaking surge in COVID as a “pandemic of the unvaccinated.”
While it may serve to further divide red and blue states, I disagree with the assertion that the current surge in cases is driven simply by the unvaccinated. Why? First, the premise would assume complete efficacy with our vaccinated population, which is statistically incorrect (at least 15 million of the U.S. population never completed a second round of injections), which means they were not considered “fully vaccinated.”
Alternately, we need to examine what has occurred in nations with significantly higher vaccination rates than ours (the United Kingdom and Israel) to realize that variants have overrun the dramatic success achieved in those countries as well. Israel, once considered to be the most vaccinated country in the world, is facing a brutal fourth wave of COVID that has sent the country spiraling into another heartbreaking lockdown.
The unvaccinated could hardly be blamed for what is happening in either of these highly vaccinated countries.
The concept of blame
So why use blame? It defeats the purpose of encouraging those who are hesitant or possibly misinformed or disenfranchised to move forward. It lacks compassion. It does not encompass the art and science of nursing (for example, the University of Southern Indiana), such as those that hospitals have used to frame optimal nursing care. I abhor the idea of labeling because it denies the prospect of future comprehension.
Labeling reminds me of one of the saddest cases in my career.
An unfortunate case
I was the nurse caring for a man from a motor vehicular accident where an entire family was brutally killed. My patient was alleged to be the cause, with a blood alcohol level of 0.40%+ post hydration, intubated and ventilated, with a flailed chest and multiple orthopedic injuries as well as blunt head trauma. He was secured to the bed with handcuffs, although that was unnecessary. Multiple times I was asked how I could possibly care for such an individual, by the police and even a few colleagues. But it was not my place to judge the man.
He was in pain, and he was dying. I comforted him for the 2 weeks it took his battered body to pass into the next realm. No one visited him except the police, eagerly waiting for the man to wake up to explain the tragic events that occurred. It was my job to ease what pain I could and protect him from labels. Did he deserve the labels? Who knew? I did not care. I cared about his writhing and his physical anguish.
The comparison
Blame did not help the situation then, nor does it help us move forward now. As nurses, we seek to work within a framework of understanding. As we tire of caring for thousands of COVID patients, we do not stop to ask if they “deserve” care or if they have taken precautions and lived reasonably prior to seeking assistance for disease. We would not be nurses if we did this.
Think about Gov. Greg Abbott, who has asked that Texans not be allowed to mandate masks for children returning to school. He has recently been diagnosed with COVID, despite assuring the public he is fully vaccinated. Politically, his diagnosis could be visualized as a fiasco for a purple state where he has been adamant in denying the efficacy of masks for children.
Yet, his diagnosis should not be fodder for the press. The first concern should be his health and well-being, similar for any man of his age and potential comorbidity.
Conclusion
We should be people first, human beings that remain interconnected by our need for care and survival, not conservatives, independents, or liberals, not “vaccinated or unvaccinated,” not seen as “breakthrough” infections, or the immunosuppressed possibly unable to mount a robust response to COVID.
Labels do not define the ability to effectively defeat coronavirus or variants, as highly vaccinated countries have demonstrated in recent months. We are in the midst of a global pandemic, and the battle is raging onward.
In fact, the longer this pandemic continues, the more likely it is we will need to live with this as an endemic disease, so we should stop blaming those who become ill and need support.
It could be any of us.
A version of this article first appeared on Medscape.com.