Thrombosis

Background: Chronic kidney disease (CKD) is both a prothrombotic state and a condition with an elevated bleeding risk that increases in a linear fashion as estimated glomerular filtration rate (eGFR) decreases. These features of the disease along with the exclusion of patients with CKD from most anticoagulation trials have resulted in uncertainty about overall risks and benefits of anticoagulant use in this population.

The most compelling data were seen in the management of atrial fibrillation in early-stage CKD (five studies representing 11,332 patients) in which high-dose DOACs were associated with a lower risk for stroke or systemic embolism (risk ratio, 0.79; 95% confidence interval, 0.66-0.92), hemorrhagic stroke (RR, 0.48; 95% CI, 0.30-0.76), and all-cause death (RR, 0.88; 95% CI, 0.78-0.99). Overall stroke reduction was primarily hemorrhagic, and DOACs were equivalent to vitamin K antagonists (VKAs) for ischemic stroke risk.

The analysis also suggests that, in CKD, DOACs may reduce major bleeding when compared with VKAs across a variety of indications, though that finding was not statistically significant.

Efficacy of DOACs, compared with VKAs, in treatment of venous thromboembolism was uncertain, and patients with end-stage kidney disease and advanced CKD (creatinine clearance, less than 25 mL/min) were excluded from all trials comparing DOACs with VKAs, with limited overall data in these populations.

Bottom line: For patients with atrial fibrillation and early-stage CKD, direct oral anticoagulants show a promising risk-benefit profile when compared with vitamin K antagonists. Very few data are available on the safety and efficacy of anticoagulants in patients with advanced CKD and end-stage kidney disease.

Citation: Ha JT et al. Benefits and harms of oral anticoagulant therapy in chronic kidney disease. Ann Intern Med. 2019 Aug 6;171(3):181-9.

Dr. Herrle is a hospitalist at Maine Medical Center in Portland and at Stephens Memorial Hospital in Norway, Maine.

Background: Chronic kidney disease (CKD) is both a prothrombotic state and a condition with an elevated bleeding risk that increases in a linear fashion as estimated glomerular filtration rate (eGFR) decreases. These features of the disease along with the exclusion of patients with CKD from most anticoagulation trials have resulted in uncertainty about overall risks and benefits of anticoagulant use in this population.

The most compelling data were seen in the management of atrial fibrillation in early-stage CKD (five studies representing 11,332 patients) in which high-dose DOACs were associated with a lower risk for stroke or systemic embolism (risk ratio, 0.79; 95% confidence interval, 0.66-0.92), hemorrhagic stroke (RR, 0.48; 95% CI, 0.30-0.76), and all-cause death (RR, 0.88; 95% CI, 0.78-0.99). Overall stroke reduction was primarily hemorrhagic, and DOACs were equivalent to vitamin K antagonists (VKAs) for ischemic stroke risk.

The analysis also suggests that, in CKD, DOACs may reduce major bleeding when compared with VKAs across a variety of indications, though that finding was not statistically significant.

Efficacy of DOACs, compared with VKAs, in treatment of venous thromboembolism was uncertain, and patients with end-stage kidney disease and advanced CKD (creatinine clearance, less than 25 mL/min) were excluded from all trials comparing DOACs with VKAs, with limited overall data in these populations.

Bottom line: For patients with atrial fibrillation and early-stage CKD, direct oral anticoagulants show a promising risk-benefit profile when compared with vitamin K antagonists. Very few data are available on the safety and efficacy of anticoagulants in patients with advanced CKD and end-stage kidney disease.

Citation: Ha JT et al. Benefits and harms of oral anticoagulant therapy in chronic kidney disease. Ann Intern Med. 2019 Aug 6;171(3):181-9.

Dr. Herrle is a hospitalist at Maine Medical Center in Portland and at Stephens Memorial Hospital in Norway, Maine.

Background: Chronic kidney disease (CKD) is both a prothrombotic state and a condition with an elevated bleeding risk that increases in a linear fashion as estimated glomerular filtration rate (eGFR) decreases. These features of the disease along with the exclusion of patients with CKD from most anticoagulation trials have resulted in uncertainty about overall risks and benefits of anticoagulant use in this population.

The most compelling data were seen in the management of atrial fibrillation in early-stage CKD (five studies representing 11,332 patients) in which high-dose DOACs were associated with a lower risk for stroke or systemic embolism (risk ratio, 0.79; 95% confidence interval, 0.66-0.92), hemorrhagic stroke (RR, 0.48; 95% CI, 0.30-0.76), and all-cause death (RR, 0.88; 95% CI, 0.78-0.99). Overall stroke reduction was primarily hemorrhagic, and DOACs were equivalent to vitamin K antagonists (VKAs) for ischemic stroke risk.

The analysis also suggests that, in CKD, DOACs may reduce major bleeding when compared with VKAs across a variety of indications, though that finding was not statistically significant.

Efficacy of DOACs, compared with VKAs, in treatment of venous thromboembolism was uncertain, and patients with end-stage kidney disease and advanced CKD (creatinine clearance, less than 25 mL/min) were excluded from all trials comparing DOACs with VKAs, with limited overall data in these populations.

Bottom line: For patients with atrial fibrillation and early-stage CKD, direct oral anticoagulants show a promising risk-benefit profile when compared with vitamin K antagonists. Very few data are available on the safety and efficacy of anticoagulants in patients with advanced CKD and end-stage kidney disease.

Citation: Ha JT et al. Benefits and harms of oral anticoagulant therapy in chronic kidney disease. Ann Intern Med. 2019 Aug 6;171(3):181-9.

Dr. Herrle is a hospitalist at Maine Medical Center in Portland and at Stephens Memorial Hospital in Norway, Maine.

Clinical question: Is it safe to adopt a standardized approach to direct oral anticoagulant (DOAC) interruption for patients with atrial fibrillation (AFib) who are undergoing elective surgeries/procedures?

The primary clinical outcomes were major bleeding and arterial thromboembolism. Authors determined safety by comparing to expected outcome rates derived from research on perioperative warfarin management.

They found that all three drugs were associated with acceptable rates of arterial thromboembolism (apixaban 0.2%, dabigatran 0.6%, rivaroxaban 0.4%). The rates of major bleeding observed with each drug (apixaban 0.6% low-risk procedures, 3% high-risk procedures; dabigatran 0.9% both low- and high-risk procedures; and rivaroxaban 1.3% low-risk procedures, 3% high-risk procedures) were similar to those in the BRIDGE trial (patients on warfarin who were not bridged perioperatively). However, it must still be noted that only dabigatran met the authors’ predetermined definition of safety for major bleeding.

Limitations include the lack of true control rates for major bleeding and stroke, the relatively low mean CHADS2-Va2Sc of 3.3-3.5, and that greater than 95% of patients were white.

Bottom line: For patients with moderate-risk atrial fibrillation, a standardized approach to DOAC interruption in the perioperative period that omits bridging along with coagulation function testing appears safe in this preliminary study.

Citation: Douketis JD et al. Perioperative management of patients with atrial fibrillation receiving a direct oral anticoagulant. JAMA Intern Med. 2019 Aug 5. doi: 10.1001/jamainternmed.2019.2431.

Dr. Gordon is a hospitalist at Maine Medical Center in Portland.

Clinical question: Is it safe to adopt a standardized approach to direct oral anticoagulant (DOAC) interruption for patients with atrial fibrillation (AFib) who are undergoing elective surgeries/procedures?

The primary clinical outcomes were major bleeding and arterial thromboembolism. Authors determined safety by comparing to expected outcome rates derived from research on perioperative warfarin management.

They found that all three drugs were associated with acceptable rates of arterial thromboembolism (apixaban 0.2%, dabigatran 0.6%, rivaroxaban 0.4%). The rates of major bleeding observed with each drug (apixaban 0.6% low-risk procedures, 3% high-risk procedures; dabigatran 0.9% both low- and high-risk procedures; and rivaroxaban 1.3% low-risk procedures, 3% high-risk procedures) were similar to those in the BRIDGE trial (patients on warfarin who were not bridged perioperatively). However, it must still be noted that only dabigatran met the authors’ predetermined definition of safety for major bleeding.

Limitations include the lack of true control rates for major bleeding and stroke, the relatively low mean CHADS2-Va2Sc of 3.3-3.5, and that greater than 95% of patients were white.

Bottom line: For patients with moderate-risk atrial fibrillation, a standardized approach to DOAC interruption in the perioperative period that omits bridging along with coagulation function testing appears safe in this preliminary study.

Citation: Douketis JD et al. Perioperative management of patients with atrial fibrillation receiving a direct oral anticoagulant. JAMA Intern Med. 2019 Aug 5. doi: 10.1001/jamainternmed.2019.2431.

Dr. Gordon is a hospitalist at Maine Medical Center in Portland.

Clinical question: Is it safe to adopt a standardized approach to direct oral anticoagulant (DOAC) interruption for patients with atrial fibrillation (AFib) who are undergoing elective surgeries/procedures?

The primary clinical outcomes were major bleeding and arterial thromboembolism. Authors determined safety by comparing to expected outcome rates derived from research on perioperative warfarin management.

They found that all three drugs were associated with acceptable rates of arterial thromboembolism (apixaban 0.2%, dabigatran 0.6%, rivaroxaban 0.4%). The rates of major bleeding observed with each drug (apixaban 0.6% low-risk procedures, 3% high-risk procedures; dabigatran 0.9% both low- and high-risk procedures; and rivaroxaban 1.3% low-risk procedures, 3% high-risk procedures) were similar to those in the BRIDGE trial (patients on warfarin who were not bridged perioperatively). However, it must still be noted that only dabigatran met the authors’ predetermined definition of safety for major bleeding.

Limitations include the lack of true control rates for major bleeding and stroke, the relatively low mean CHADS2-Va2Sc of 3.3-3.5, and that greater than 95% of patients were white.

Bottom line: For patients with moderate-risk atrial fibrillation, a standardized approach to DOAC interruption in the perioperative period that omits bridging along with coagulation function testing appears safe in this preliminary study.

Citation: Douketis JD et al. Perioperative management of patients with atrial fibrillation receiving a direct oral anticoagulant. JAMA Intern Med. 2019 Aug 5. doi: 10.1001/jamainternmed.2019.2431.

Dr. Gordon is a hospitalist at Maine Medical Center in Portland.

Left atrial appendage occlusion (LAAO) for high-risk atrial fibrillation seems to prevent stroke as well as direct oral anticoagulation (DOAC) with a lower risk of major bleeding, according to results of a European study.

And although some experts question the strength of the conclusions, a lead researcher contends the study may provide enough support for interventional cardiologists to consider LAAO in selected patients until randomized clinical trials yield stronger evidence.

“The results suggest LAAO to be superior to DOAC in AF patients who have a predicted high risk of stroke and bleeding and adds to the evidence that LAAO is a promising stroke prevention strategy in selected AF patients,” said lead investigator Jens Erik Nielsen-Kudsk, MD, DMSc, a cardiologist at Aarhus University Hospital in Denmark.

Dr. Nielsen-Kudsk and colleagues wrote in JACC: Cardiovascular Interventions that this is the largest comparative study of LAAO vs. DOAC to date, but they also acknowledged the study limitations: its observational design, unaccounted confounders, potential selection bias, and disparities in the nature of the comparative datasets (a multination cohort vs. a single national registry).

Observational registry study shows 43% reduction in primary outcome

The study compared outcomes of 1,078 patients from the Amulet Observational Study who had LAAO during June 2015–September 2016 with 1,184 patients on DOAC therapy selected by propensity score matching from two Danish national registries. The LAAO population was prospectively enrolled at 61 centers in 17 countries. The study population had a high risk of stroke and bleeding; about one-third had a previous stroke and about three-quarters had a prior bleeding episode. The average age was 75 years.

The LAAO group had almost half the rate of the primary outcome – either stroke, major bleeding, or all-cause death – 256 vs. 461 events in the DOAC group with median follow-up of 2 years. The annualized event rate was significantly lower for the LAAO group: 14.5 vs. 25.7 per 100 patient years in the DOAC group. The researchers calculated the LAAO group had a relative 43% reduction risk.

Of the LAAO group, 155 patients (14.5%) died in the follow-up period, 35% of them from a cardiovascular cause, whereas 308 (26%) of patients in the DOAC group died, with a similar percentage, 36%, from a cardiovascular cause.

Using data from the Danish Cause of Death Registry, the study determined cause of death in the DOAC patients on a more granular level: 9.5% of the deaths were from vascular disease and 4.5% from stroke (the remainder in both groups were from noncardiovascular events).

Stroke incidence was similar between the two groups: 39 in the LAAO group vs. 37 in DOAC patients, conferring an 11% greater risk in the former. The risk of major bleeding and all-cause mortality were significantly lower in LAAO patients, 37% and 47%, respectively. However, 50% of DOAC patients had discontinued therapy after a year of follow-up, and 58% had done so after 2 years.

Dr. Nielsen-Kudsk noted that the findings line up with those from the smaller PRAQUE-17 study comparing LAAO and DOAC. He added that his group is participating in two larger RCTs, CATALYST and CHAMPION-AF, evaluating LAAO and medical therapy in about 6,000 patients combined.

“It will take at least 2 to 5 years before we have data from these randomized LAAO trials,” Dr. Nielsen-Kudsk said. “Meanwhile, based on data from three prior randomized clinical trials, propensity-score matched studies and data from large registries, LAAO should be considered in clinical practice for patients who have a high risk of bleeding or who for any other reason are unsuitable for long-term DOAC treatment.”

Noncompliance to DOAC therapy a concern

In an invited commentary, Mohamad Alkhouli, MD, of the Mayo Medical School, Rochester, Minn., wrote, “These findings provide reassuring evidence supporting the efficacy of LAAO despite the remaining challenges with this therapy.”

However, Dr. Alkhouli pointed out that the high rate of noncompliance among AF patients on DOAC can be a confounding factor for interpreting the efficacy of therapy. “This highlights the challenges of comparing LAAO to DOAC, considering that many patients are actually not on effective anticoagulation, but also suggests a possible real important role for LAAO in addressing the unmet need in stroke prevention in nonvalvular atrial fibrillation,” he said in an interview.

“The study showed a very good safety profile for LAAO,” Dr. Alkhouli added. “However, we should remember that this was an observational study without routine temporal imaging and a relatively short-term follow- up.”

Methods ‘severely flawed’

John Mandrola, MD, an electrophysiologist at Baptist Health in Louisville, Ky., said the study methodology was “severely flawed,” citing its nonrandomized nature and enrollment of only patients with successful implants in the LAAO group. “You have to take all patients who had attempted implants,” he said. Further, the study may be subject to selection bias based on how patients were recruited for the Ampulet Observational Study.

“Comparing LAAO to DOAC is a vital clinical question,” said Dr. Mandrola. “It simply cannot be answered with observational methods like this. It requires a properly powered RCT.”

Dr. Alkhouli said he’s looking forward to results from five large RCTS evaluating LAAO due in 3-5 years. “Until the results of those trials are out, careful patient selection and shared decision-making should continue to govern the rational dissipation of LAAO as a stroke prevention strategy,” he said.

Novo Nordisk Research Foundation supported the study and Abbott provided a grant. Dr. Nielsen-Kudsk disclosed financial relationships with Abbott and Boston Scientific. Coauthors disclosed relationships with Abbott, Boston Scientific, Bayer Vital, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi-Sankyo, Medtronic, Pfizer, Portolo, and Sanofi.

Dr. Alkhouli disclosed a relationship with Boston Scientific. Dr. Mandrola has no relevant disclosures. He is chief cardiology correspondent for Medscape.com. MDedge is a member of the Medscape Professional Network.

Left atrial appendage occlusion (LAAO) for high-risk atrial fibrillation seems to prevent stroke as well as direct oral anticoagulation (DOAC) with a lower risk of major bleeding, according to results of a European study.

And although some experts question the strength of the conclusions, a lead researcher contends the study may provide enough support for interventional cardiologists to consider LAAO in selected patients until randomized clinical trials yield stronger evidence.

“The results suggest LAAO to be superior to DOAC in AF patients who have a predicted high risk of stroke and bleeding and adds to the evidence that LAAO is a promising stroke prevention strategy in selected AF patients,” said lead investigator Jens Erik Nielsen-Kudsk, MD, DMSc, a cardiologist at Aarhus University Hospital in Denmark.

Dr. Nielsen-Kudsk and colleagues wrote in JACC: Cardiovascular Interventions that this is the largest comparative study of LAAO vs. DOAC to date, but they also acknowledged the study limitations: its observational design, unaccounted confounders, potential selection bias, and disparities in the nature of the comparative datasets (a multination cohort vs. a single national registry).

Observational registry study shows 43% reduction in primary outcome

The study compared outcomes of 1,078 patients from the Amulet Observational Study who had LAAO during June 2015–September 2016 with 1,184 patients on DOAC therapy selected by propensity score matching from two Danish national registries. The LAAO population was prospectively enrolled at 61 centers in 17 countries. The study population had a high risk of stroke and bleeding; about one-third had a previous stroke and about three-quarters had a prior bleeding episode. The average age was 75 years.

The LAAO group had almost half the rate of the primary outcome – either stroke, major bleeding, or all-cause death – 256 vs. 461 events in the DOAC group with median follow-up of 2 years. The annualized event rate was significantly lower for the LAAO group: 14.5 vs. 25.7 per 100 patient years in the DOAC group. The researchers calculated the LAAO group had a relative 43% reduction risk.

Of the LAAO group, 155 patients (14.5%) died in the follow-up period, 35% of them from a cardiovascular cause, whereas 308 (26%) of patients in the DOAC group died, with a similar percentage, 36%, from a cardiovascular cause.

Using data from the Danish Cause of Death Registry, the study determined cause of death in the DOAC patients on a more granular level: 9.5% of the deaths were from vascular disease and 4.5% from stroke (the remainder in both groups were from noncardiovascular events).

Stroke incidence was similar between the two groups: 39 in the LAAO group vs. 37 in DOAC patients, conferring an 11% greater risk in the former. The risk of major bleeding and all-cause mortality were significantly lower in LAAO patients, 37% and 47%, respectively. However, 50% of DOAC patients had discontinued therapy after a year of follow-up, and 58% had done so after 2 years.

Dr. Nielsen-Kudsk noted that the findings line up with those from the smaller PRAQUE-17 study comparing LAAO and DOAC. He added that his group is participating in two larger RCTs, CATALYST and CHAMPION-AF, evaluating LAAO and medical therapy in about 6,000 patients combined.

“It will take at least 2 to 5 years before we have data from these randomized LAAO trials,” Dr. Nielsen-Kudsk said. “Meanwhile, based on data from three prior randomized clinical trials, propensity-score matched studies and data from large registries, LAAO should be considered in clinical practice for patients who have a high risk of bleeding or who for any other reason are unsuitable for long-term DOAC treatment.”

Noncompliance to DOAC therapy a concern

In an invited commentary, Mohamad Alkhouli, MD, of the Mayo Medical School, Rochester, Minn., wrote, “These findings provide reassuring evidence supporting the efficacy of LAAO despite the remaining challenges with this therapy.”

However, Dr. Alkhouli pointed out that the high rate of noncompliance among AF patients on DOAC can be a confounding factor for interpreting the efficacy of therapy. “This highlights the challenges of comparing LAAO to DOAC, considering that many patients are actually not on effective anticoagulation, but also suggests a possible real important role for LAAO in addressing the unmet need in stroke prevention in nonvalvular atrial fibrillation,” he said in an interview.

“The study showed a very good safety profile for LAAO,” Dr. Alkhouli added. “However, we should remember that this was an observational study without routine temporal imaging and a relatively short-term follow- up.”

Methods ‘severely flawed’

John Mandrola, MD, an electrophysiologist at Baptist Health in Louisville, Ky., said the study methodology was “severely flawed,” citing its nonrandomized nature and enrollment of only patients with successful implants in the LAAO group. “You have to take all patients who had attempted implants,” he said. Further, the study may be subject to selection bias based on how patients were recruited for the Ampulet Observational Study.

“Comparing LAAO to DOAC is a vital clinical question,” said Dr. Mandrola. “It simply cannot be answered with observational methods like this. It requires a properly powered RCT.”

Dr. Alkhouli said he’s looking forward to results from five large RCTS evaluating LAAO due in 3-5 years. “Until the results of those trials are out, careful patient selection and shared decision-making should continue to govern the rational dissipation of LAAO as a stroke prevention strategy,” he said.

Novo Nordisk Research Foundation supported the study and Abbott provided a grant. Dr. Nielsen-Kudsk disclosed financial relationships with Abbott and Boston Scientific. Coauthors disclosed relationships with Abbott, Boston Scientific, Bayer Vital, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi-Sankyo, Medtronic, Pfizer, Portolo, and Sanofi.

Dr. Alkhouli disclosed a relationship with Boston Scientific. Dr. Mandrola has no relevant disclosures. He is chief cardiology correspondent for Medscape.com. MDedge is a member of the Medscape Professional Network.

Left atrial appendage occlusion (LAAO) for high-risk atrial fibrillation seems to prevent stroke as well as direct oral anticoagulation (DOAC) with a lower risk of major bleeding, according to results of a European study.

And although some experts question the strength of the conclusions, a lead researcher contends the study may provide enough support for interventional cardiologists to consider LAAO in selected patients until randomized clinical trials yield stronger evidence.

“The results suggest LAAO to be superior to DOAC in AF patients who have a predicted high risk of stroke and bleeding and adds to the evidence that LAAO is a promising stroke prevention strategy in selected AF patients,” said lead investigator Jens Erik Nielsen-Kudsk, MD, DMSc, a cardiologist at Aarhus University Hospital in Denmark.

Dr. Nielsen-Kudsk and colleagues wrote in JACC: Cardiovascular Interventions that this is the largest comparative study of LAAO vs. DOAC to date, but they also acknowledged the study limitations: its observational design, unaccounted confounders, potential selection bias, and disparities in the nature of the comparative datasets (a multination cohort vs. a single national registry).

Observational registry study shows 43% reduction in primary outcome

The study compared outcomes of 1,078 patients from the Amulet Observational Study who had LAAO during June 2015–September 2016 with 1,184 patients on DOAC therapy selected by propensity score matching from two Danish national registries. The LAAO population was prospectively enrolled at 61 centers in 17 countries. The study population had a high risk of stroke and bleeding; about one-third had a previous stroke and about three-quarters had a prior bleeding episode. The average age was 75 years.

The LAAO group had almost half the rate of the primary outcome – either stroke, major bleeding, or all-cause death – 256 vs. 461 events in the DOAC group with median follow-up of 2 years. The annualized event rate was significantly lower for the LAAO group: 14.5 vs. 25.7 per 100 patient years in the DOAC group. The researchers calculated the LAAO group had a relative 43% reduction risk.

Of the LAAO group, 155 patients (14.5%) died in the follow-up period, 35% of them from a cardiovascular cause, whereas 308 (26%) of patients in the DOAC group died, with a similar percentage, 36%, from a cardiovascular cause.

Using data from the Danish Cause of Death Registry, the study determined cause of death in the DOAC patients on a more granular level: 9.5% of the deaths were from vascular disease and 4.5% from stroke (the remainder in both groups were from noncardiovascular events).

Stroke incidence was similar between the two groups: 39 in the LAAO group vs. 37 in DOAC patients, conferring an 11% greater risk in the former. The risk of major bleeding and all-cause mortality were significantly lower in LAAO patients, 37% and 47%, respectively. However, 50% of DOAC patients had discontinued therapy after a year of follow-up, and 58% had done so after 2 years.

Dr. Nielsen-Kudsk noted that the findings line up with those from the smaller PRAQUE-17 study comparing LAAO and DOAC. He added that his group is participating in two larger RCTs, CATALYST and CHAMPION-AF, evaluating LAAO and medical therapy in about 6,000 patients combined.

“It will take at least 2 to 5 years before we have data from these randomized LAAO trials,” Dr. Nielsen-Kudsk said. “Meanwhile, based on data from three prior randomized clinical trials, propensity-score matched studies and data from large registries, LAAO should be considered in clinical practice for patients who have a high risk of bleeding or who for any other reason are unsuitable for long-term DOAC treatment.”

Noncompliance to DOAC therapy a concern

In an invited commentary, Mohamad Alkhouli, MD, of the Mayo Medical School, Rochester, Minn., wrote, “These findings provide reassuring evidence supporting the efficacy of LAAO despite the remaining challenges with this therapy.”

However, Dr. Alkhouli pointed out that the high rate of noncompliance among AF patients on DOAC can be a confounding factor for interpreting the efficacy of therapy. “This highlights the challenges of comparing LAAO to DOAC, considering that many patients are actually not on effective anticoagulation, but also suggests a possible real important role for LAAO in addressing the unmet need in stroke prevention in nonvalvular atrial fibrillation,” he said in an interview.

“The study showed a very good safety profile for LAAO,” Dr. Alkhouli added. “However, we should remember that this was an observational study without routine temporal imaging and a relatively short-term follow- up.”

Methods ‘severely flawed’

John Mandrola, MD, an electrophysiologist at Baptist Health in Louisville, Ky., said the study methodology was “severely flawed,” citing its nonrandomized nature and enrollment of only patients with successful implants in the LAAO group. “You have to take all patients who had attempted implants,” he said. Further, the study may be subject to selection bias based on how patients were recruited for the Ampulet Observational Study.

“Comparing LAAO to DOAC is a vital clinical question,” said Dr. Mandrola. “It simply cannot be answered with observational methods like this. It requires a properly powered RCT.”

Dr. Alkhouli said he’s looking forward to results from five large RCTS evaluating LAAO due in 3-5 years. “Until the results of those trials are out, careful patient selection and shared decision-making should continue to govern the rational dissipation of LAAO as a stroke prevention strategy,” he said.

Novo Nordisk Research Foundation supported the study and Abbott provided a grant. Dr. Nielsen-Kudsk disclosed financial relationships with Abbott and Boston Scientific. Coauthors disclosed relationships with Abbott, Boston Scientific, Bayer Vital, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi-Sankyo, Medtronic, Pfizer, Portolo, and Sanofi.

Dr. Alkhouli disclosed a relationship with Boston Scientific. Dr. Mandrola has no relevant disclosures. He is chief cardiology correspondent for Medscape.com. MDedge is a member of the Medscape Professional Network.

There is no question that COVID-19 infection increases the risks of serious thromboembolic events, including pulmonary embolism (PE), but it also increases the risk of bleeding, complicating the benefit-to-risk calculations for anticoagulation, according to a review of data at the virtual Going Back to the Heart of Cardiology meeting.

“Bleeding is a significant cause of morbidity in patients with COVID-19, and this is an important concept to appreciate,” reported Rachel P. Rosovsky, MD, director of thrombosis research, Massachusetts General Hospital, Boston.

At least five guidelines, including those issued by the American College of Cardiology, International Society on Thrombosis and Haemostasis (ISTH), and the American College of Chest Physicians, have recently addressed anticoagulation in patients infected with COVID-19, but there are “substantive differences” between them, according to Dr. Rosovsky. The reason is that they are essentially no high quality trials to guide practice. Rather, the recommendations are based primarily on retrospective studies and expert opinion.

The single most common theme from the guidelines is that anticoagulation must be individualized to balance patient-specific risks of venous thromboembolism (VTE) and bleeding, said Dr. Rosovsky, whose group published a recent comparison of these guidelines (Flaczyk A et al. Crit Care 2020;24:559).

Although there is general consensus that all hospitalized patients with COVID-19 should receive anticoagulation unless there are contraindications, there are differences in the recommended intensity of the anticoagulation for different risk groups and there is even less is less consensus on the need to anticoagulate outpatients or patients after discharge, according to Dr. Rosovsky

In her own center, the standard is a prophylactic dose of low molecular weight heparin (LMWH) in an algorithm that calls for dose adjustments for some groups such as those with renal impairment or obesity. Alternative forms of anticoagulation are recommended for patients with a history of thrombocytopenia or are at high risk for hemorrhage. Full dose LMWH is recommended in patients already on an oral anticoagulant at time of hospitalization.

“The biggest question right now is when to consider increasing from a prophylactic dose to intermediate or full dose anticoagulation in high risk patients, especially those in the ICU patients,” Dr. Rosovsky said.

Current practices are diverse, according to a recently published survey led by Dr. Rosovsky (Rosovsky RP et al. Res Pract Thromb Haemost. 2020;4:969-83). According to the survey, which had responses from more than 500 physicians in 41 countries, 30% of centers escalate from a prophylactic dose of anticoagulation to an intermediate dose when patients move to the ICU. Although not all answered this question, 25% reported that they do not escalate at ICU transfer. For 15% of respondents, dose escalation is being offered to patients with a D-dimer exceeding six-times the upper limit of normal.

These practices have developed in the absence of prospective clinical trials, which are urgently needed, according to Dr. Rosovsky. The reason that trials specific to COVID-19 are particularly important is that this infection also engenders a high risk of major bleeding.

For example, in a multicenter retrospective study of 400 hospital-admitted COVID-19 patients the rates of major bleeding was 4.8% or exactly the same as the rate of radiographically confirmed VTE. At 7.6%, the rates of VTE and major bleeding were also exactly the same for ICU patients (Al-Samkari H et al. Blood 2020;136:489-500).

“An elevated D-dimer was a marker for both VTE and major bleeding,” reported Dr. Rosovsky, who was the senior author of this study. On the basis of odds ratio (OR), the risk of VTE was increased more than six-fold (OR, 6.79) and the risk of major bleeding by more than three-fold (OR, 3.56) when the D-dimer exceeded 2,500 ng/mL.

The risk of VTE from COVID-19 infection is well documented. For example, autopsy studies have shown widespread thrombosis, including PE, in patients who have died from COVID-19 infection, according to Dr. Rosovsky.

There is also evidence of benefit from anticoagulation. In an retrospective study from China undertaken early in the pandemic, there was no overall mortality benefit at 28 days among those who did receive LMWH when compared to those who did not, but there was a 20% absolute mortality benefit (52.4% vs. 32.8%; P = .017) in those with a D-dimer six-fold ULN (Tang N et al. J Thromb Haemost 2020;18:1094-9).

These types of data support the use of anticoagulation to manage VTE risk in at least some patients, but the reported rates of VTE across institutions and across inpatient and outpatient settings have varied “dramatically,” according to Dr. Rosovsky. The balance of VTE and major bleeding is delicate. In one retrospective study, the mortality advantage for therapeutic versus prophylactic dose of LMWH did not reach statistical significance, but the rate of major bleeding was nearly doubled (3.0% vs. 1.7%) (Nadkarni GN et al J Am Coll Cardiol 2020;76:1815-26).

Because of the many variables that might affect risk of VTE and risk of major bleeding in any individual patient, the benefit-to-risk calculation of anticoagulation is “complex,” according to Dr. Rosovsky. It is for this reason she urged clinicians to consider entering patients into clinical trials designed to generate evidence-based answers.

There is large and growing body of retrospective data that have helped characterize the risk of VTE and bleeding in patients with COVID-19, but “there is no substitute for a well-controlled clinical trial,” agreed Robert A. Harrington, MD, chairman of the department of medicine, Stanford (Calif.) University.

He and the comoderator of the session in which these data were presented agreed that anticoagulation must be administered within a narrow therapeutic window that will be best defined through controlled trial designs.

“There is a significant risk of doing harm,” said Fatima Rodriguez, MD, assistant professor of cardiology at Stanford University. She seconded the critical role of trial participation when possible and the need for clinical trials to better guide treatment decisions.

The meeting was sponsored by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

There is no question that COVID-19 infection increases the risks of serious thromboembolic events, including pulmonary embolism (PE), but it also increases the risk of bleeding, complicating the benefit-to-risk calculations for anticoagulation, according to a review of data at the virtual Going Back to the Heart of Cardiology meeting.

“Bleeding is a significant cause of morbidity in patients with COVID-19, and this is an important concept to appreciate,” reported Rachel P. Rosovsky, MD, director of thrombosis research, Massachusetts General Hospital, Boston.

At least five guidelines, including those issued by the American College of Cardiology, International Society on Thrombosis and Haemostasis (ISTH), and the American College of Chest Physicians, have recently addressed anticoagulation in patients infected with COVID-19, but there are “substantive differences” between them, according to Dr. Rosovsky. The reason is that they are essentially no high quality trials to guide practice. Rather, the recommendations are based primarily on retrospective studies and expert opinion.

The single most common theme from the guidelines is that anticoagulation must be individualized to balance patient-specific risks of venous thromboembolism (VTE) and bleeding, said Dr. Rosovsky, whose group published a recent comparison of these guidelines (Flaczyk A et al. Crit Care 2020;24:559).

Although there is general consensus that all hospitalized patients with COVID-19 should receive anticoagulation unless there are contraindications, there are differences in the recommended intensity of the anticoagulation for different risk groups and there is even less is less consensus on the need to anticoagulate outpatients or patients after discharge, according to Dr. Rosovsky

In her own center, the standard is a prophylactic dose of low molecular weight heparin (LMWH) in an algorithm that calls for dose adjustments for some groups such as those with renal impairment or obesity. Alternative forms of anticoagulation are recommended for patients with a history of thrombocytopenia or are at high risk for hemorrhage. Full dose LMWH is recommended in patients already on an oral anticoagulant at time of hospitalization.

“The biggest question right now is when to consider increasing from a prophylactic dose to intermediate or full dose anticoagulation in high risk patients, especially those in the ICU patients,” Dr. Rosovsky said.

Current practices are diverse, according to a recently published survey led by Dr. Rosovsky (Rosovsky RP et al. Res Pract Thromb Haemost. 2020;4:969-83). According to the survey, which had responses from more than 500 physicians in 41 countries, 30% of centers escalate from a prophylactic dose of anticoagulation to an intermediate dose when patients move to the ICU. Although not all answered this question, 25% reported that they do not escalate at ICU transfer. For 15% of respondents, dose escalation is being offered to patients with a D-dimer exceeding six-times the upper limit of normal.

These practices have developed in the absence of prospective clinical trials, which are urgently needed, according to Dr. Rosovsky. The reason that trials specific to COVID-19 are particularly important is that this infection also engenders a high risk of major bleeding.

For example, in a multicenter retrospective study of 400 hospital-admitted COVID-19 patients the rates of major bleeding was 4.8% or exactly the same as the rate of radiographically confirmed VTE. At 7.6%, the rates of VTE and major bleeding were also exactly the same for ICU patients (Al-Samkari H et al. Blood 2020;136:489-500).

“An elevated D-dimer was a marker for both VTE and major bleeding,” reported Dr. Rosovsky, who was the senior author of this study. On the basis of odds ratio (OR), the risk of VTE was increased more than six-fold (OR, 6.79) and the risk of major bleeding by more than three-fold (OR, 3.56) when the D-dimer exceeded 2,500 ng/mL.

The risk of VTE from COVID-19 infection is well documented. For example, autopsy studies have shown widespread thrombosis, including PE, in patients who have died from COVID-19 infection, according to Dr. Rosovsky.

There is also evidence of benefit from anticoagulation. In an retrospective study from China undertaken early in the pandemic, there was no overall mortality benefit at 28 days among those who did receive LMWH when compared to those who did not, but there was a 20% absolute mortality benefit (52.4% vs. 32.8%; P = .017) in those with a D-dimer six-fold ULN (Tang N et al. J Thromb Haemost 2020;18:1094-9).

These types of data support the use of anticoagulation to manage VTE risk in at least some patients, but the reported rates of VTE across institutions and across inpatient and outpatient settings have varied “dramatically,” according to Dr. Rosovsky. The balance of VTE and major bleeding is delicate. In one retrospective study, the mortality advantage for therapeutic versus prophylactic dose of LMWH did not reach statistical significance, but the rate of major bleeding was nearly doubled (3.0% vs. 1.7%) (Nadkarni GN et al J Am Coll Cardiol 2020;76:1815-26).

Because of the many variables that might affect risk of VTE and risk of major bleeding in any individual patient, the benefit-to-risk calculation of anticoagulation is “complex,” according to Dr. Rosovsky. It is for this reason she urged clinicians to consider entering patients into clinical trials designed to generate evidence-based answers.

There is large and growing body of retrospective data that have helped characterize the risk of VTE and bleeding in patients with COVID-19, but “there is no substitute for a well-controlled clinical trial,” agreed Robert A. Harrington, MD, chairman of the department of medicine, Stanford (Calif.) University.

He and the comoderator of the session in which these data were presented agreed that anticoagulation must be administered within a narrow therapeutic window that will be best defined through controlled trial designs.

“There is a significant risk of doing harm,” said Fatima Rodriguez, MD, assistant professor of cardiology at Stanford University. She seconded the critical role of trial participation when possible and the need for clinical trials to better guide treatment decisions.

The meeting was sponsored by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

There is no question that COVID-19 infection increases the risks of serious thromboembolic events, including pulmonary embolism (PE), but it also increases the risk of bleeding, complicating the benefit-to-risk calculations for anticoagulation, according to a review of data at the virtual Going Back to the Heart of Cardiology meeting.

“Bleeding is a significant cause of morbidity in patients with COVID-19, and this is an important concept to appreciate,” reported Rachel P. Rosovsky, MD, director of thrombosis research, Massachusetts General Hospital, Boston.

At least five guidelines, including those issued by the American College of Cardiology, International Society on Thrombosis and Haemostasis (ISTH), and the American College of Chest Physicians, have recently addressed anticoagulation in patients infected with COVID-19, but there are “substantive differences” between them, according to Dr. Rosovsky. The reason is that they are essentially no high quality trials to guide practice. Rather, the recommendations are based primarily on retrospective studies and expert opinion.

The single most common theme from the guidelines is that anticoagulation must be individualized to balance patient-specific risks of venous thromboembolism (VTE) and bleeding, said Dr. Rosovsky, whose group published a recent comparison of these guidelines (Flaczyk A et al. Crit Care 2020;24:559).

Although there is general consensus that all hospitalized patients with COVID-19 should receive anticoagulation unless there are contraindications, there are differences in the recommended intensity of the anticoagulation for different risk groups and there is even less is less consensus on the need to anticoagulate outpatients or patients after discharge, according to Dr. Rosovsky

In her own center, the standard is a prophylactic dose of low molecular weight heparin (LMWH) in an algorithm that calls for dose adjustments for some groups such as those with renal impairment or obesity. Alternative forms of anticoagulation are recommended for patients with a history of thrombocytopenia or are at high risk for hemorrhage. Full dose LMWH is recommended in patients already on an oral anticoagulant at time of hospitalization.

“The biggest question right now is when to consider increasing from a prophylactic dose to intermediate or full dose anticoagulation in high risk patients, especially those in the ICU patients,” Dr. Rosovsky said.

Current practices are diverse, according to a recently published survey led by Dr. Rosovsky (Rosovsky RP et al. Res Pract Thromb Haemost. 2020;4:969-83). According to the survey, which had responses from more than 500 physicians in 41 countries, 30% of centers escalate from a prophylactic dose of anticoagulation to an intermediate dose when patients move to the ICU. Although not all answered this question, 25% reported that they do not escalate at ICU transfer. For 15% of respondents, dose escalation is being offered to patients with a D-dimer exceeding six-times the upper limit of normal.

These practices have developed in the absence of prospective clinical trials, which are urgently needed, according to Dr. Rosovsky. The reason that trials specific to COVID-19 are particularly important is that this infection also engenders a high risk of major bleeding.

For example, in a multicenter retrospective study of 400 hospital-admitted COVID-19 patients the rates of major bleeding was 4.8% or exactly the same as the rate of radiographically confirmed VTE. At 7.6%, the rates of VTE and major bleeding were also exactly the same for ICU patients (Al-Samkari H et al. Blood 2020;136:489-500).

“An elevated D-dimer was a marker for both VTE and major bleeding,” reported Dr. Rosovsky, who was the senior author of this study. On the basis of odds ratio (OR), the risk of VTE was increased more than six-fold (OR, 6.79) and the risk of major bleeding by more than three-fold (OR, 3.56) when the D-dimer exceeded 2,500 ng/mL.

The risk of VTE from COVID-19 infection is well documented. For example, autopsy studies have shown widespread thrombosis, including PE, in patients who have died from COVID-19 infection, according to Dr. Rosovsky.

There is also evidence of benefit from anticoagulation. In an retrospective study from China undertaken early in the pandemic, there was no overall mortality benefit at 28 days among those who did receive LMWH when compared to those who did not, but there was a 20% absolute mortality benefit (52.4% vs. 32.8%; P = .017) in those with a D-dimer six-fold ULN (Tang N et al. J Thromb Haemost 2020;18:1094-9).

These types of data support the use of anticoagulation to manage VTE risk in at least some patients, but the reported rates of VTE across institutions and across inpatient and outpatient settings have varied “dramatically,” according to Dr. Rosovsky. The balance of VTE and major bleeding is delicate. In one retrospective study, the mortality advantage for therapeutic versus prophylactic dose of LMWH did not reach statistical significance, but the rate of major bleeding was nearly doubled (3.0% vs. 1.7%) (Nadkarni GN et al J Am Coll Cardiol 2020;76:1815-26).

Because of the many variables that might affect risk of VTE and risk of major bleeding in any individual patient, the benefit-to-risk calculation of anticoagulation is “complex,” according to Dr. Rosovsky. It is for this reason she urged clinicians to consider entering patients into clinical trials designed to generate evidence-based answers.

There is large and growing body of retrospective data that have helped characterize the risk of VTE and bleeding in patients with COVID-19, but “there is no substitute for a well-controlled clinical trial,” agreed Robert A. Harrington, MD, chairman of the department of medicine, Stanford (Calif.) University.

He and the comoderator of the session in which these data were presented agreed that anticoagulation must be administered within a narrow therapeutic window that will be best defined through controlled trial designs.

“There is a significant risk of doing harm,” said Fatima Rodriguez, MD, assistant professor of cardiology at Stanford University. She seconded the critical role of trial participation when possible and the need for clinical trials to better guide treatment decisions.

The meeting was sponsored by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

The real strength of the 4T score for heparin-induced thrombocytopenia (HIT) is its negative predictive value, according to hematologist Adam Cuker, MD, of the department of medicine at the University of Pennsylvania, Philadelphia.

The score assigns patients points based on degree of thrombocytopenia, timing of platelet count fall in relation to heparin exposure, presence of thrombosis and other sequelae, and the likelihood of other causes of thrombocytopenia.

A low score – 3 points or less – has a negative predictive value of 99.8%, “so HIT is basically ruled out; you do not need to order lab testing for HIT or manage the patient empirically for HIT,” and should look for other causes of thrombocytopenia, said Dr. Cuker, lead author of the American Society of Hematology’s most recent HIT guidelines.

Intermediate scores of 4 or 5 points, and high scores of 6-8 points, are a different story. The positive predictive value of an intermediate score is only 14%, and of a high score, 64%, so although they don’t confirm the diagnosis, “you have to take the possibility of HIT seriously.” Discontinue heparin, start a nonheparin anticoagulant, and order a HIT immunoassay. If it’s positive, order a functional assay to confirm the diagnosis, he said.

Suspicion of HIT “is perhaps the most common consult that we get on the hematology service. These are tough consults because it is a high-stakes decision.” There is about a 6% risk of thromboembolism, amputation, and death for every day treatment is delayed. “On the other hand, the nonheparin anticoagulants are expensive, and they carry about a 1% daily risk of major bleeding,” Dr. Cuker explained during his presentation at the 2020 Update in Nonneoplastic Hematology virtual conference.

ELISA immunoassay detects antiplatelet factor 4 heparin antibodies but doesn’t tell whether or not they are able to activate platelets and cause HIT. Functional tests such as the serotonin-release assay detect only those antibodies able to do so, but the assays are difficult to perform, and often require samples to be sent out to a reference lab.

ASH did not specify a particular nonheparin anticoagulant in its 2018 guidelines because “the best choice for your patient” depends on which drugs you have available, your familiarity with them, and patient factors, Dr. Cuker said at the conference sponsored by MedscapeLive.

It makes sense, for instance, to use a short-acting agent such as argatroban or bivalirudin in patients who are critically ill, at high risk of bleeding, or likely to need an urgent unplanned procedure. Fondaparinux or direct oral anticoagulants (DOACs) make sense if patients are clinically stable with good organ function and no more than average bleeding risk, because they are easier to administer and facilitate transition to the outpatient setting.

DOACs are newcomers to ASH’s guidelines. Just 81 patients had been reported in the literature when they were being drafted, but only 2 patients had recurrence or progression of thromboembolic events, and there were no major bleeds. The results compared favorably with other options.

The studies were subject to selection and reporting biases, “but, nonetheless, the panel felt the results were positive enough that DOACs ought to be listed as an option,” Dr. Cuker said.

The guidelines note that parenteral options may be the best choice for life- or limb-threatening thrombosis “because few such patients have been treated with a DOAC.” Anticoagulation must continue until platelet counts recover.

Dr. Cuker is a consultant for Synergy and has institutional research support from Alexion, Bayer, Sanofi, and other companies. MedscapeLive and this news organization are owned by the same parent company.

[email protected]

The real strength of the 4T score for heparin-induced thrombocytopenia (HIT) is its negative predictive value, according to hematologist Adam Cuker, MD, of the department of medicine at the University of Pennsylvania, Philadelphia.

The score assigns patients points based on degree of thrombocytopenia, timing of platelet count fall in relation to heparin exposure, presence of thrombosis and other sequelae, and the likelihood of other causes of thrombocytopenia.

A low score – 3 points or less – has a negative predictive value of 99.8%, “so HIT is basically ruled out; you do not need to order lab testing for HIT or manage the patient empirically for HIT,” and should look for other causes of thrombocytopenia, said Dr. Cuker, lead author of the American Society of Hematology’s most recent HIT guidelines.

Intermediate scores of 4 or 5 points, and high scores of 6-8 points, are a different story. The positive predictive value of an intermediate score is only 14%, and of a high score, 64%, so although they don’t confirm the diagnosis, “you have to take the possibility of HIT seriously.” Discontinue heparin, start a nonheparin anticoagulant, and order a HIT immunoassay. If it’s positive, order a functional assay to confirm the diagnosis, he said.

Suspicion of HIT “is perhaps the most common consult that we get on the hematology service. These are tough consults because it is a high-stakes decision.” There is about a 6% risk of thromboembolism, amputation, and death for every day treatment is delayed. “On the other hand, the nonheparin anticoagulants are expensive, and they carry about a 1% daily risk of major bleeding,” Dr. Cuker explained during his presentation at the 2020 Update in Nonneoplastic Hematology virtual conference.

ELISA immunoassay detects antiplatelet factor 4 heparin antibodies but doesn’t tell whether or not they are able to activate platelets and cause HIT. Functional tests such as the serotonin-release assay detect only those antibodies able to do so, but the assays are difficult to perform, and often require samples to be sent out to a reference lab.

ASH did not specify a particular nonheparin anticoagulant in its 2018 guidelines because “the best choice for your patient” depends on which drugs you have available, your familiarity with them, and patient factors, Dr. Cuker said at the conference sponsored by MedscapeLive.

It makes sense, for instance, to use a short-acting agent such as argatroban or bivalirudin in patients who are critically ill, at high risk of bleeding, or likely to need an urgent unplanned procedure. Fondaparinux or direct oral anticoagulants (DOACs) make sense if patients are clinically stable with good organ function and no more than average bleeding risk, because they are easier to administer and facilitate transition to the outpatient setting.

DOACs are newcomers to ASH’s guidelines. Just 81 patients had been reported in the literature when they were being drafted, but only 2 patients had recurrence or progression of thromboembolic events, and there were no major bleeds. The results compared favorably with other options.

The studies were subject to selection and reporting biases, “but, nonetheless, the panel felt the results were positive enough that DOACs ought to be listed as an option,” Dr. Cuker said.

The guidelines note that parenteral options may be the best choice for life- or limb-threatening thrombosis “because few such patients have been treated with a DOAC.” Anticoagulation must continue until platelet counts recover.

Dr. Cuker is a consultant for Synergy and has institutional research support from Alexion, Bayer, Sanofi, and other companies. MedscapeLive and this news organization are owned by the same parent company.

[email protected]

The real strength of the 4T score for heparin-induced thrombocytopenia (HIT) is its negative predictive value, according to hematologist Adam Cuker, MD, of the department of medicine at the University of Pennsylvania, Philadelphia.

The score assigns patients points based on degree of thrombocytopenia, timing of platelet count fall in relation to heparin exposure, presence of thrombosis and other sequelae, and the likelihood of other causes of thrombocytopenia.

A low score – 3 points or less – has a negative predictive value of 99.8%, “so HIT is basically ruled out; you do not need to order lab testing for HIT or manage the patient empirically for HIT,” and should look for other causes of thrombocytopenia, said Dr. Cuker, lead author of the American Society of Hematology’s most recent HIT guidelines.

Intermediate scores of 4 or 5 points, and high scores of 6-8 points, are a different story. The positive predictive value of an intermediate score is only 14%, and of a high score, 64%, so although they don’t confirm the diagnosis, “you have to take the possibility of HIT seriously.” Discontinue heparin, start a nonheparin anticoagulant, and order a HIT immunoassay. If it’s positive, order a functional assay to confirm the diagnosis, he said.

Suspicion of HIT “is perhaps the most common consult that we get on the hematology service. These are tough consults because it is a high-stakes decision.” There is about a 6% risk of thromboembolism, amputation, and death for every day treatment is delayed. “On the other hand, the nonheparin anticoagulants are expensive, and they carry about a 1% daily risk of major bleeding,” Dr. Cuker explained during his presentation at the 2020 Update in Nonneoplastic Hematology virtual conference.

ELISA immunoassay detects antiplatelet factor 4 heparin antibodies but doesn’t tell whether or not they are able to activate platelets and cause HIT. Functional tests such as the serotonin-release assay detect only those antibodies able to do so, but the assays are difficult to perform, and often require samples to be sent out to a reference lab.

ASH did not specify a particular nonheparin anticoagulant in its 2018 guidelines because “the best choice for your patient” depends on which drugs you have available, your familiarity with them, and patient factors, Dr. Cuker said at the conference sponsored by MedscapeLive.

It makes sense, for instance, to use a short-acting agent such as argatroban or bivalirudin in patients who are critically ill, at high risk of bleeding, or likely to need an urgent unplanned procedure. Fondaparinux or direct oral anticoagulants (DOACs) make sense if patients are clinically stable with good organ function and no more than average bleeding risk, because they are easier to administer and facilitate transition to the outpatient setting.

DOACs are newcomers to ASH’s guidelines. Just 81 patients had been reported in the literature when they were being drafted, but only 2 patients had recurrence or progression of thromboembolic events, and there were no major bleeds. The results compared favorably with other options.

The studies were subject to selection and reporting biases, “but, nonetheless, the panel felt the results were positive enough that DOACs ought to be listed as an option,” Dr. Cuker said.

The guidelines note that parenteral options may be the best choice for life- or limb-threatening thrombosis “because few such patients have been treated with a DOAC.” Anticoagulation must continue until platelet counts recover.

Dr. Cuker is a consultant for Synergy and has institutional research support from Alexion, Bayer, Sanofi, and other companies. MedscapeLive and this news organization are owned by the same parent company.

[email protected]

Among patients taking direct oral anticoagulants (DOACs), elective endoscopy procedures carry a risk of bleeding and thromboembolic events similar to that seen in those receiving vitamin K antagonists (VKAs), according to a multicenter, prospective observational study conducted at 12 Spanish academic and community centers.

DOACs have several advantages over VKAs, including more predictable pharmacokinetic profiles and fewer food and drug interactions, but they have not been well studied in the elective endoscopy setting. Some previous studies suggested a lower risk with DOACs than with VKAs, but they were retrospective or based on administrative databases.

It also remains unclear when anticoagulant therapy should be resumed following high-risk procedures. The new study, which was led by Enrique Rodríguez de Santiago of Universidad de Alcalá (Spain) and published in Clinical Gastroenterology and Hepatology, suggested that early resumption may be safe. “It certainly showed there was an acceptable rate of clinically significant rate of bleeding for patients on anticoagulants, and the thing I appreciated the most was that there was no statistically significant difference in terms of bleeding depending on when you resumed the anticoagulant,” said Robert Jay Sealock, MD, assistant professor of medicine at Baylor College of Medicine in Houston. Dr. Sealock was not involved in the study.

The researchers examined data from 1,623 patients who underwent 1,874 endoscopic procedures. Among these patients, 62.7% were taking VKAs, and 37.3% were taking DOACs; 58.9% were men, and the mean age was 74.2 years. Overall, 75.5% were on anticoagulant therapy for atrial fibrillation.

The most common procedures were colonoscopy (68.3%) and esophagogastroduodenoscopy (27.3%).

Within 30 days, The risk of bleeding was similar between patients taking VKAs (6.2%; 95% confidence interval, 4.8-7.8%) and DOACs (6.7%; 95% CI, 4.9-9%). This was true regardless of intervention and site. Overall, 1.4% of subjects experienced a thromboembolic event (95% CI, 0.9-2.1%), and there was no significant difference between the VKA group (1.3%; 95% CI, 0.8-2.2%) and the DOAC group (1.5%; 95% CI, 0.8-2.8%).

Clinically significant gastrointestinal bleeding occurred in 6.4% of subjects (95% CI, 5.3-7.7%); 2.7% of clinically significant gastrointestinal bleeding events were intraprocedural and 4.1% were delayed. The lowest risk of bleeding occurred with diagnostic endoscopy (1.1%) and biopsy (2.2%). The risk of bleeding for high-risk procedures was 11.5% (95% CI, 9.4-14%).

The overall mortality was 1.4%, with two deaths related to thromboembolic events, both in the DOAC group. The other deaths were considered to be unrelated to the procedure or periprocedural interruption of anticoagulants.

The researchers also examined the timing of anticoagulant resumption. Overall, 59.2% of subjects received bridging therapy, including 85% of the VKA group and 16% of the DOAC group (P < .001). This was not associated with increased endoscopy-related bleeding in either the VKA (3.3% with bridging therapy vs. 6.4% without; P = .14) or the DOAC group (8.3% vs. 6.4%; P = .48).

A total of 747 patients underwent a high-risk procedure, 46.3% of patients resumed anticoagulant therapy within 24 hours of the procedure, and 46.2% between 24 and 48 hours. After inverse probability of treatment weighting adjustment, a delay in anticoagulant resumption was not associated with a reduction in the frequency of postprocedural clinically significant gastrointestinal bleeding.

Still, the research left some questions unanswered. Most of the high-risk procedures were hot (41.8%) or cold snare polypectomies (39.8%). There weren’t enough data in the study to evaluate risk in patients undergoing other high-risk procedures such as balloon dilation for strictures, endoscopic ultrasound with fine-needle aspiration, and sphincterotomy. “That’s one group that we still don’t really have enough data about, particularly those patients who are on DOACs,” said Dr. Sealock.

The study also found a high number of patients on bridging therapy. “It highlighted the fact that we probably use bridging therapy too much in patients undergoing endoscopy,” said Dr. Sealock. He recommended using tools that generate recommendations for bridging therapy and timing for withholding and resuming anticoagulants based on procedure and patient characteristics.

SOURCE: de Santiago ER et al. Clin Gastroenterol Hepatol. 2020 Dec 03. doi: 10.1016/j.cgh.2020.11.037.

Among patients taking direct oral anticoagulants (DOACs), elective endoscopy procedures carry a risk of bleeding and thromboembolic events similar to that seen in those receiving vitamin K antagonists (VKAs), according to a multicenter, prospective observational study conducted at 12 Spanish academic and community centers.

DOACs have several advantages over VKAs, including more predictable pharmacokinetic profiles and fewer food and drug interactions, but they have not been well studied in the elective endoscopy setting. Some previous studies suggested a lower risk with DOACs than with VKAs, but they were retrospective or based on administrative databases.

It also remains unclear when anticoagulant therapy should be resumed following high-risk procedures. The new study, which was led by Enrique Rodríguez de Santiago of Universidad de Alcalá (Spain) and published in Clinical Gastroenterology and Hepatology, suggested that early resumption may be safe. “It certainly showed there was an acceptable rate of clinically significant rate of bleeding for patients on anticoagulants, and the thing I appreciated the most was that there was no statistically significant difference in terms of bleeding depending on when you resumed the anticoagulant,” said Robert Jay Sealock, MD, assistant professor of medicine at Baylor College of Medicine in Houston. Dr. Sealock was not involved in the study.

The researchers examined data from 1,623 patients who underwent 1,874 endoscopic procedures. Among these patients, 62.7% were taking VKAs, and 37.3% were taking DOACs; 58.9% were men, and the mean age was 74.2 years. Overall, 75.5% were on anticoagulant therapy for atrial fibrillation.

The most common procedures were colonoscopy (68.3%) and esophagogastroduodenoscopy (27.3%).

Within 30 days, The risk of bleeding was similar between patients taking VKAs (6.2%; 95% confidence interval, 4.8-7.8%) and DOACs (6.7%; 95% CI, 4.9-9%). This was true regardless of intervention and site. Overall, 1.4% of subjects experienced a thromboembolic event (95% CI, 0.9-2.1%), and there was no significant difference between the VKA group (1.3%; 95% CI, 0.8-2.2%) and the DOAC group (1.5%; 95% CI, 0.8-2.8%).

Clinically significant gastrointestinal bleeding occurred in 6.4% of subjects (95% CI, 5.3-7.7%); 2.7% of clinically significant gastrointestinal bleeding events were intraprocedural and 4.1% were delayed. The lowest risk of bleeding occurred with diagnostic endoscopy (1.1%) and biopsy (2.2%). The risk of bleeding for high-risk procedures was 11.5% (95% CI, 9.4-14%).

The overall mortality was 1.4%, with two deaths related to thromboembolic events, both in the DOAC group. The other deaths were considered to be unrelated to the procedure or periprocedural interruption of anticoagulants.

The researchers also examined the timing of anticoagulant resumption. Overall, 59.2% of subjects received bridging therapy, including 85% of the VKA group and 16% of the DOAC group (P < .001). This was not associated with increased endoscopy-related bleeding in either the VKA (3.3% with bridging therapy vs. 6.4% without; P = .14) or the DOAC group (8.3% vs. 6.4%; P = .48).

A total of 747 patients underwent a high-risk procedure, 46.3% of patients resumed anticoagulant therapy within 24 hours of the procedure, and 46.2% between 24 and 48 hours. After inverse probability of treatment weighting adjustment, a delay in anticoagulant resumption was not associated with a reduction in the frequency of postprocedural clinically significant gastrointestinal bleeding.

Still, the research left some questions unanswered. Most of the high-risk procedures were hot (41.8%) or cold snare polypectomies (39.8%). There weren’t enough data in the study to evaluate risk in patients undergoing other high-risk procedures such as balloon dilation for strictures, endoscopic ultrasound with fine-needle aspiration, and sphincterotomy. “That’s one group that we still don’t really have enough data about, particularly those patients who are on DOACs,” said Dr. Sealock.

The study also found a high number of patients on bridging therapy. “It highlighted the fact that we probably use bridging therapy too much in patients undergoing endoscopy,” said Dr. Sealock. He recommended using tools that generate recommendations for bridging therapy and timing for withholding and resuming anticoagulants based on procedure and patient characteristics.

SOURCE: de Santiago ER et al. Clin Gastroenterol Hepatol. 2020 Dec 03. doi: 10.1016/j.cgh.2020.11.037.

Among patients taking direct oral anticoagulants (DOACs), elective endoscopy procedures carry a risk of bleeding and thromboembolic events similar to that seen in those receiving vitamin K antagonists (VKAs), according to a multicenter, prospective observational study conducted at 12 Spanish academic and community centers.

DOACs have several advantages over VKAs, including more predictable pharmacokinetic profiles and fewer food and drug interactions, but they have not been well studied in the elective endoscopy setting. Some previous studies suggested a lower risk with DOACs than with VKAs, but they were retrospective or based on administrative databases.

It also remains unclear when anticoagulant therapy should be resumed following high-risk procedures. The new study, which was led by Enrique Rodríguez de Santiago of Universidad de Alcalá (Spain) and published in Clinical Gastroenterology and Hepatology, suggested that early resumption may be safe. “It certainly showed there was an acceptable rate of clinically significant rate of bleeding for patients on anticoagulants, and the thing I appreciated the most was that there was no statistically significant difference in terms of bleeding depending on when you resumed the anticoagulant,” said Robert Jay Sealock, MD, assistant professor of medicine at Baylor College of Medicine in Houston. Dr. Sealock was not involved in the study.

The researchers examined data from 1,623 patients who underwent 1,874 endoscopic procedures. Among these patients, 62.7% were taking VKAs, and 37.3% were taking DOACs; 58.9% were men, and the mean age was 74.2 years. Overall, 75.5% were on anticoagulant therapy for atrial fibrillation.

The most common procedures were colonoscopy (68.3%) and esophagogastroduodenoscopy (27.3%).

Within 30 days, The risk of bleeding was similar between patients taking VKAs (6.2%; 95% confidence interval, 4.8-7.8%) and DOACs (6.7%; 95% CI, 4.9-9%). This was true regardless of intervention and site. Overall, 1.4% of subjects experienced a thromboembolic event (95% CI, 0.9-2.1%), and there was no significant difference between the VKA group (1.3%; 95% CI, 0.8-2.2%) and the DOAC group (1.5%; 95% CI, 0.8-2.8%).

Clinically significant gastrointestinal bleeding occurred in 6.4% of subjects (95% CI, 5.3-7.7%); 2.7% of clinically significant gastrointestinal bleeding events were intraprocedural and 4.1% were delayed. The lowest risk of bleeding occurred with diagnostic endoscopy (1.1%) and biopsy (2.2%). The risk of bleeding for high-risk procedures was 11.5% (95% CI, 9.4-14%).

The overall mortality was 1.4%, with two deaths related to thromboembolic events, both in the DOAC group. The other deaths were considered to be unrelated to the procedure or periprocedural interruption of anticoagulants.

The researchers also examined the timing of anticoagulant resumption. Overall, 59.2% of subjects received bridging therapy, including 85% of the VKA group and 16% of the DOAC group (P < .001). This was not associated with increased endoscopy-related bleeding in either the VKA (3.3% with bridging therapy vs. 6.4% without; P = .14) or the DOAC group (8.3% vs. 6.4%; P = .48).

A total of 747 patients underwent a high-risk procedure, 46.3% of patients resumed anticoagulant therapy within 24 hours of the procedure, and 46.2% between 24 and 48 hours. After inverse probability of treatment weighting adjustment, a delay in anticoagulant resumption was not associated with a reduction in the frequency of postprocedural clinically significant gastrointestinal bleeding.

Still, the research left some questions unanswered. Most of the high-risk procedures were hot (41.8%) or cold snare polypectomies (39.8%). There weren’t enough data in the study to evaluate risk in patients undergoing other high-risk procedures such as balloon dilation for strictures, endoscopic ultrasound with fine-needle aspiration, and sphincterotomy. “That’s one group that we still don’t really have enough data about, particularly those patients who are on DOACs,” said Dr. Sealock.

The study also found a high number of patients on bridging therapy. “It highlighted the fact that we probably use bridging therapy too much in patients undergoing endoscopy,” said Dr. Sealock. He recommended using tools that generate recommendations for bridging therapy and timing for withholding and resuming anticoagulants based on procedure and patient characteristics.

SOURCE: de Santiago ER et al. Clin Gastroenterol Hepatol. 2020 Dec 03. doi: 10.1016/j.cgh.2020.11.037.

Researchers in Madrid may have found a clue to the pathogenesis of ST-segment elevation myocardial infarction (STEMI) in patients with COVID-19; it might also offer a therapeutic target to counter the hypercoagulability seen with COVID-19.

In a case series of five patients with COVID-19 who had an STEMI, neutrophil extracellular traps (NETs) were detected in coronary thrombi of all five patients. The median density was 66%, which is significantly higher than that seen in a historical series of patients with STEMI. In that series, NETs were found in only two-thirds of patients; in that series, the median density was 19%.

In the patients with COVID-19 and STEMI and in the patients reported in the prepandemic historical series from 2015, intracoronary aspirates were obtained during percutaneous coronary intervention using a thrombus aspiration device.

Histologically, findings in the patients from 2015 differed from those of patients with COVID-19. In the patients with COVID, thrombi were composed mostly of fibrin and polymorphonuclear cells. None showed fragments of atherosclerotic plaque or iron deposits indicative of previous episodes of plaque rupture. In contrast, 65% of thrombi from the 2015 series contained plaque fragments.

Ana Blasco, MD, PhD, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, and colleagues report their findings in an article published online Dec. 29 in JAMA Cardiology.

Commenting on the findings in an interview, Irene Lang, MD, from the Medical University of Vienna said, “This is really a very small series, purely observational, and suffering from the problem that acute STEMI is uncommon in COVID-19, but it does serve to demonstrate once more the abundance of NETs in acute myocardial infarction.”

“NETs are very much at the cutting edge of thrombosis research, and NET formation provides yet another link between inflammation and clot formation,” added Peter Libby, MD, from Harvard Medical School and Brigham and Women’s Hospital, Boston.

“Multiple observations have shown thrombosis of arteries large and small, microvessels, and veins in COVID-19. The observations of Blasco et al. add to the growing literature about NETs as contributors to the havoc wrought in multiple organs in advanced COVID-19,” he added in an email exchange with this news organization.

Neither Dr. Lang nor Dr. Libby were involved in this research; both have been actively studying NETs and their contribution to cardiothrombotic disease in recent years.

NETs are newly recognized contributors to venous and arterial thrombosis. These weblike DNA strands are extruded by activated or dying neutrophils and have protein mediators that ensnare pathogens while minimizing damage to the host cell.

First described in 2004, exaggerated NET formation has also been linked to the initiation and accretion of inflammation and thrombosis.

“NETs thus furnish a previously unsuspected link between inflammation, innate immunity, thrombosis, oxidative stress, and cardiovascular diseases,” Dr. Libby and his coauthors wrote in an article on the topic published in Circulation Research earlier this year.

Limiting NET formation or “dissolving” existing NETs could provide a therapeutic avenue not just for patients with COVID-19 but for all patients with thrombotic disease.

“The concept of NETs as a therapeutic target is appealing, in and out of COVID times,” said Dr. Lang.

“I personally believe that the work helps to raise awareness for the potential use of deoxyribonuclease (DNase), an enzyme that acts to clear NETs by dissolving the DNA strands, in the acute treatment of STEMI. Rapid injection of engineered recombinant DNases could potentially wipe away coronary obstructions, ideally before they may cause damage to the myocardium,” she added.

Dr. Blasco and colleagues and Dr. Lang have disclosed no relevant financial relationships. Dr. Libby is an unpaid consultant or member of the advisory board for a number of companies.

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

Researchers in Madrid may have found a clue to the pathogenesis of ST-segment elevation myocardial infarction (STEMI) in patients with COVID-19; it might also offer a therapeutic target to counter the hypercoagulability seen with COVID-19.

In a case series of five patients with COVID-19 who had an STEMI, neutrophil extracellular traps (NETs) were detected in coronary thrombi of all five patients. The median density was 66%, which is significantly higher than that seen in a historical series of patients with STEMI. In that series, NETs were found in only two-thirds of patients; in that series, the median density was 19%.

In the patients with COVID-19 and STEMI and in the patients reported in the prepandemic historical series from 2015, intracoronary aspirates were obtained during percutaneous coronary intervention using a thrombus aspiration device.

Histologically, findings in the patients from 2015 differed from those of patients with COVID-19. In the patients with COVID, thrombi were composed mostly of fibrin and polymorphonuclear cells. None showed fragments of atherosclerotic plaque or iron deposits indicative of previous episodes of plaque rupture. In contrast, 65% of thrombi from the 2015 series contained plaque fragments.

Ana Blasco, MD, PhD, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, and colleagues report their findings in an article published online Dec. 29 in JAMA Cardiology.

Commenting on the findings in an interview, Irene Lang, MD, from the Medical University of Vienna said, “This is really a very small series, purely observational, and suffering from the problem that acute STEMI is uncommon in COVID-19, but it does serve to demonstrate once more the abundance of NETs in acute myocardial infarction.”

“NETs are very much at the cutting edge of thrombosis research, and NET formation provides yet another link between inflammation and clot formation,” added Peter Libby, MD, from Harvard Medical School and Brigham and Women’s Hospital, Boston.

“Multiple observations have shown thrombosis of arteries large and small, microvessels, and veins in COVID-19. The observations of Blasco et al. add to the growing literature about NETs as contributors to the havoc wrought in multiple organs in advanced COVID-19,” he added in an email exchange with this news organization.

Neither Dr. Lang nor Dr. Libby were involved in this research; both have been actively studying NETs and their contribution to cardiothrombotic disease in recent years.

NETs are newly recognized contributors to venous and arterial thrombosis. These weblike DNA strands are extruded by activated or dying neutrophils and have protein mediators that ensnare pathogens while minimizing damage to the host cell.

First described in 2004, exaggerated NET formation has also been linked to the initiation and accretion of inflammation and thrombosis.

“NETs thus furnish a previously unsuspected link between inflammation, innate immunity, thrombosis, oxidative stress, and cardiovascular diseases,” Dr. Libby and his coauthors wrote in an article on the topic published in Circulation Research earlier this year.

Limiting NET formation or “dissolving” existing NETs could provide a therapeutic avenue not just for patients with COVID-19 but for all patients with thrombotic disease.

“The concept of NETs as a therapeutic target is appealing, in and out of COVID times,” said Dr. Lang.

“I personally believe that the work helps to raise awareness for the potential use of deoxyribonuclease (DNase), an enzyme that acts to clear NETs by dissolving the DNA strands, in the acute treatment of STEMI. Rapid injection of engineered recombinant DNases could potentially wipe away coronary obstructions, ideally before they may cause damage to the myocardium,” she added.

Dr. Blasco and colleagues and Dr. Lang have disclosed no relevant financial relationships. Dr. Libby is an unpaid consultant or member of the advisory board for a number of companies.

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

Researchers in Madrid may have found a clue to the pathogenesis of ST-segment elevation myocardial infarction (STEMI) in patients with COVID-19; it might also offer a therapeutic target to counter the hypercoagulability seen with COVID-19.

In a case series of five patients with COVID-19 who had an STEMI, neutrophil extracellular traps (NETs) were detected in coronary thrombi of all five patients. The median density was 66%, which is significantly higher than that seen in a historical series of patients with STEMI. In that series, NETs were found in only two-thirds of patients; in that series, the median density was 19%.

In the patients with COVID-19 and STEMI and in the patients reported in the prepandemic historical series from 2015, intracoronary aspirates were obtained during percutaneous coronary intervention using a thrombus aspiration device.

Histologically, findings in the patients from 2015 differed from those of patients with COVID-19. In the patients with COVID, thrombi were composed mostly of fibrin and polymorphonuclear cells. None showed fragments of atherosclerotic plaque or iron deposits indicative of previous episodes of plaque rupture. In contrast, 65% of thrombi from the 2015 series contained plaque fragments.

Ana Blasco, MD, PhD, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, and colleagues report their findings in an article published online Dec. 29 in JAMA Cardiology.

Commenting on the findings in an interview, Irene Lang, MD, from the Medical University of Vienna said, “This is really a very small series, purely observational, and suffering from the problem that acute STEMI is uncommon in COVID-19, but it does serve to demonstrate once more the abundance of NETs in acute myocardial infarction.”

“NETs are very much at the cutting edge of thrombosis research, and NET formation provides yet another link between inflammation and clot formation,” added Peter Libby, MD, from Harvard Medical School and Brigham and Women’s Hospital, Boston.

“Multiple observations have shown thrombosis of arteries large and small, microvessels, and veins in COVID-19. The observations of Blasco et al. add to the growing literature about NETs as contributors to the havoc wrought in multiple organs in advanced COVID-19,” he added in an email exchange with this news organization.

Neither Dr. Lang nor Dr. Libby were involved in this research; both have been actively studying NETs and their contribution to cardiothrombotic disease in recent years.

NETs are newly recognized contributors to venous and arterial thrombosis. These weblike DNA strands are extruded by activated or dying neutrophils and have protein mediators that ensnare pathogens while minimizing damage to the host cell.

First described in 2004, exaggerated NET formation has also been linked to the initiation and accretion of inflammation and thrombosis.

“NETs thus furnish a previously unsuspected link between inflammation, innate immunity, thrombosis, oxidative stress, and cardiovascular diseases,” Dr. Libby and his coauthors wrote in an article on the topic published in Circulation Research earlier this year.

Limiting NET formation or “dissolving” existing NETs could provide a therapeutic avenue not just for patients with COVID-19 but for all patients with thrombotic disease.

“The concept of NETs as a therapeutic target is appealing, in and out of COVID times,” said Dr. Lang.

“I personally believe that the work helps to raise awareness for the potential use of deoxyribonuclease (DNase), an enzyme that acts to clear NETs by dissolving the DNA strands, in the acute treatment of STEMI. Rapid injection of engineered recombinant DNases could potentially wipe away coronary obstructions, ideally before they may cause damage to the myocardium,” she added.

Dr. Blasco and colleagues and Dr. Lang have disclosed no relevant financial relationships. Dr. Libby is an unpaid consultant or member of the advisory board for a number of companies.

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

Parts of three linked studies investigating increased levels of anticoagulation in hospitalized COVID-19 patients have been “paused” because of futility and safety concerns, a statement from the U.S. National Heart, Lung, and Blood Institute (NHLBI) confirms.

The trials involved are the REMAP-CAP, ACTIV-4, and ATTACC studies.

All three trials have paused enrollment of critically ill COVID-19 patients requiring intensive care unit support for whom therapeutic doses of anticoagulation drugs did not reduce the need for organ support, the NHLBI statement notes.

The statement also says that a potential for harm in this subgroup could not be excluded, noting that increased bleeding is a known complication of full-dose anticoagulation. The trials are working urgently to undertake additional analyses, which will be made available as soon as possible.   

The three clinical trial platforms are working together to test the effects of full therapeutic doses of anticoagulants vs. lower prophylactic doses in COVID-19 patients.

Informed by the deliberations of the data safety monitoring boards of these trials, all of the trial sites have paused enrollment of the most critically ill hospitalized patients with COVID-19. 

Enrollment continues in the trials for moderately ill hospitalized COVID-19 patients, the statement notes.  

“Whether the use of full-dose compared to low-dose anticoagulants leads to better outcomes in hospitalized patients with less COVID-19 severe disease remains a very important question,” the NHLBI statement says.

Patients who require full dose anticoagulants for another medical indication are not included in these trials.

The statement explains that COVID-19 is associated with significant inflammation and clinical and pathologic evidence of widespread blood clots. These trials were launched because clinicians have observed that many patients ill with COVID-19, including those who have died from the disease, formed blood clots throughout their bodies, even in their smallest blood vessels. This unusual clotting can cause multiple health complications, including lung failure, myocardial infarction, and stroke. 

The three trials are the result of a collaboration between major international partners. The trials include: the Randomized, Embedded, Multi-factorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) Therapeutic Anticoagulation; Accelerating COVID-19 Therapeutic Interventions and Vaccines-4 (ACTIV-4) Antithrombotics Inpatient; and Antithrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC).

The trials, which span four continents, have the common goal of assessing the benefit of full doses of anticoagulants to treat moderately ill or critically ill adults hospitalized for COVID-19, compared with a lower dose often used to prevent blood clots in hospitalized patients.

In the United States, the ACTIV-4 trial is being led by a collaborative effort involving a number of universities, including the University of Pittsburgh and New York University.  

The trials are supported by multiple international funding organizations including the National Institutes of Health, Canadian Institutes of Health Research, the National Institute for Health Research (UK), the National Health and Medical Research Council (Australia), and the PREPARE and RECOVER consortia (European Union).

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

Parts of three linked studies investigating increased levels of anticoagulation in hospitalized COVID-19 patients have been “paused” because of futility and safety concerns, a statement from the U.S. National Heart, Lung, and Blood Institute (NHLBI) confirms.

The trials involved are the REMAP-CAP, ACTIV-4, and ATTACC studies.

All three trials have paused enrollment of critically ill COVID-19 patients requiring intensive care unit support for whom therapeutic doses of anticoagulation drugs did not reduce the need for organ support, the NHLBI statement notes.

The statement also says that a potential for harm in this subgroup could not be excluded, noting that increased bleeding is a known complication of full-dose anticoagulation. The trials are working urgently to undertake additional analyses, which will be made available as soon as possible.   

The three clinical trial platforms are working together to test the effects of full therapeutic doses of anticoagulants vs. lower prophylactic doses in COVID-19 patients.

Informed by the deliberations of the data safety monitoring boards of these trials, all of the trial sites have paused enrollment of the most critically ill hospitalized patients with COVID-19. 

Enrollment continues in the trials for moderately ill hospitalized COVID-19 patients, the statement notes.  

“Whether the use of full-dose compared to low-dose anticoagulants leads to better outcomes in hospitalized patients with less COVID-19 severe disease remains a very important question,” the NHLBI statement says.

Patients who require full dose anticoagulants for another medical indication are not included in these trials.

The statement explains that COVID-19 is associated with significant inflammation and clinical and pathologic evidence of widespread blood clots. These trials were launched because clinicians have observed that many patients ill with COVID-19, including those who have died from the disease, formed blood clots throughout their bodies, even in their smallest blood vessels. This unusual clotting can cause multiple health complications, including lung failure, myocardial infarction, and stroke. 

The three trials are the result of a collaboration between major international partners. The trials include: the Randomized, Embedded, Multi-factorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) Therapeutic Anticoagulation; Accelerating COVID-19 Therapeutic Interventions and Vaccines-4 (ACTIV-4) Antithrombotics Inpatient; and Antithrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC).

The trials, which span four continents, have the common goal of assessing the benefit of full doses of anticoagulants to treat moderately ill or critically ill adults hospitalized for COVID-19, compared with a lower dose often used to prevent blood clots in hospitalized patients.

In the United States, the ACTIV-4 trial is being led by a collaborative effort involving a number of universities, including the University of Pittsburgh and New York University.  

The trials are supported by multiple international funding organizations including the National Institutes of Health, Canadian Institutes of Health Research, the National Institute for Health Research (UK), the National Health and Medical Research Council (Australia), and the PREPARE and RECOVER consortia (European Union).

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

Parts of three linked studies investigating increased levels of anticoagulation in hospitalized COVID-19 patients have been “paused” because of futility and safety concerns, a statement from the U.S. National Heart, Lung, and Blood Institute (NHLBI) confirms.

The trials involved are the REMAP-CAP, ACTIV-4, and ATTACC studies.

All three trials have paused enrollment of critically ill COVID-19 patients requiring intensive care unit support for whom therapeutic doses of anticoagulation drugs did not reduce the need for organ support, the NHLBI statement notes.

The statement also says that a potential for harm in this subgroup could not be excluded, noting that increased bleeding is a known complication of full-dose anticoagulation. The trials are working urgently to undertake additional analyses, which will be made available as soon as possible.   

The three clinical trial platforms are working together to test the effects of full therapeutic doses of anticoagulants vs. lower prophylactic doses in COVID-19 patients.

Informed by the deliberations of the data safety monitoring boards of these trials, all of the trial sites have paused enrollment of the most critically ill hospitalized patients with COVID-19. 

Enrollment continues in the trials for moderately ill hospitalized COVID-19 patients, the statement notes.  

“Whether the use of full-dose compared to low-dose anticoagulants leads to better outcomes in hospitalized patients with less COVID-19 severe disease remains a very important question,” the NHLBI statement says.

Patients who require full dose anticoagulants for another medical indication are not included in these trials.

The statement explains that COVID-19 is associated with significant inflammation and clinical and pathologic evidence of widespread blood clots. These trials were launched because clinicians have observed that many patients ill with COVID-19, including those who have died from the disease, formed blood clots throughout their bodies, even in their smallest blood vessels. This unusual clotting can cause multiple health complications, including lung failure, myocardial infarction, and stroke. 

The three trials are the result of a collaboration between major international partners. The trials include: the Randomized, Embedded, Multi-factorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) Therapeutic Anticoagulation; Accelerating COVID-19 Therapeutic Interventions and Vaccines-4 (ACTIV-4) Antithrombotics Inpatient; and Antithrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC).

The trials, which span four continents, have the common goal of assessing the benefit of full doses of anticoagulants to treat moderately ill or critically ill adults hospitalized for COVID-19, compared with a lower dose often used to prevent blood clots in hospitalized patients.

In the United States, the ACTIV-4 trial is being led by a collaborative effort involving a number of universities, including the University of Pittsburgh and New York University.  

The trials are supported by multiple international funding organizations including the National Institutes of Health, Canadian Institutes of Health Research, the National Institute for Health Research (UK), the National Health and Medical Research Council (Australia), and the PREPARE and RECOVER consortia (European Union).

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

Each year in the United States, approximately one to two out of every thousand people suffer from venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism. The American Society of Hematology (ASH) issued new guidelines for the management of VTE, including primary treatment, secondary prevention, and treatment of recurrent events, earlier this year.

These guidelines, which were recently published in Blood Advances (Ortel T L et al. Blood Adv 2020 doi: 10.1182/bloodadvances.2020001830), include 28 recommendations.

How to treat uncomplicated patients

For uncomplicated deep vein thrombosis (DVT) and/or pulmonary embolism (PE), the guidelines suggest treating patients at home rather than in the hospital. This is especially important for family physicians to note as many of these patients will now be the responsibility of the primary care doctor to treat and follow. Patients treated at home can avoid the risk of nosocomial infections, especially in the days of COVID-19. Evidence also suggests that being treated at home was shown to reduce the risk of PE versus being treated in the hospital. It is, therefore, crucial that family physicians know which patients are low versus high risk.

Further, the guidelines suggest that these patients with low risk of complications are better treated with direct oral anticoagulants (DOACs) instead of vitamin K antagonists, such as Coumadin.

Medication-related suggestions

The guidelines also suggest that no DOAC is preferred over another. Since DOACs are relatively newer agents, family doctors need to become comfortable with their use. For proximal DVTs, anticoagulation alone can be used without thrombolytics.

Family physicians are often tasked with the decision on when to stop anticoagulation. The authors recommend against using diagnostic tests such as D-Dimer or ultrasound to decide when to stop these medications in low-risk patients. In patients at risk of recurrent VTE due to chronic medical conditions, it is suggested to continue anti-coagulants indefinitely. While anticoagulant therapy effectively reduces risk of VTE, it does increase the risk of bleeding events.

The guidelines are quite extensive and specific in their recommendations and family physicians need to understand them. We are often the first ones in the medical system to diagnose VTE, and it is quite possible to keep these patients home, thereby eliminating risks they may encounter by being hospitalized. In addition, the recommendation regarding the use of DOACs may ease some of the burden of monitoring patients on long-term Coumadin. These medications do not come without risks, and we must be comfortable evaluating for any complications. In our current health care system, different insurance companies have different formularies making it necessary for us to know all these medications.

In the past, the diagnosis of PE and even a DVT would mean a hospital stay. We now know, and these guidelines reaffirm, that this is not necessary in uncomplicated cases.

In addition to diagnosing VTE, family physicians are also tasked with following up with patients who were hospitalized or started on treatment by other physicians. We need to know the plan on when to stop the medication or when to reevaluate its use. Patients often bring this question to us, and these guidelines will help us answer that question.

Many patients who have more complicated medical conditions often see multiple specialists. The ASH recommendations help standardize the care of these patients across specialties.

What the recommendations are missing

As family doctors, we often treat patients with multiple comorbidities. These guidelines do not make recommendations for patients with cancer, who are at high risk of VTE events. Some patients also have conditions that increase their risk of bleeding or have contraindications to the use of anticoagulants. It would be helpful to have more recommendations for both of these types of patients in addition to the use of inferior vena cava filter in patients with proximal DVT. The document is also missing recommendations for pregnant patients, which would be useful.

Overall, these guidelines include much of what we already do in our practices while doing a great job of incorporating the newer DOACs. These guidelines are easy for family physicians to put into practice.
 

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].

Each year in the United States, approximately one to two out of every thousand people suffer from venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism. The American Society of Hematology (ASH) issued new guidelines for the management of VTE, including primary treatment, secondary prevention, and treatment of recurrent events, earlier this year.

These guidelines, which were recently published in Blood Advances (Ortel T L et al. Blood Adv 2020 doi: 10.1182/bloodadvances.2020001830), include 28 recommendations.

How to treat uncomplicated patients

For uncomplicated deep vein thrombosis (DVT) and/or pulmonary embolism (PE), the guidelines suggest treating patients at home rather than in the hospital. This is especially important for family physicians to note as many of these patients will now be the responsibility of the primary care doctor to treat and follow. Patients treated at home can avoid the risk of nosocomial infections, especially in the days of COVID-19. Evidence also suggests that being treated at home was shown to reduce the risk of PE versus being treated in the hospital. It is, therefore, crucial that family physicians know which patients are low versus high risk.

Further, the guidelines suggest that these patients with low risk of complications are better treated with direct oral anticoagulants (DOACs) instead of vitamin K antagonists, such as Coumadin.

Medication-related suggestions

The guidelines also suggest that no DOAC is preferred over another. Since DOACs are relatively newer agents, family doctors need to become comfortable with their use. For proximal DVTs, anticoagulation alone can be used without thrombolytics.

Family physicians are often tasked with the decision on when to stop anticoagulation. The authors recommend against using diagnostic tests such as D-Dimer or ultrasound to decide when to stop these medications in low-risk patients. In patients at risk of recurrent VTE due to chronic medical conditions, it is suggested to continue anti-coagulants indefinitely. While anticoagulant therapy effectively reduces risk of VTE, it does increase the risk of bleeding events.

The guidelines are quite extensive and specific in their recommendations and family physicians need to understand them. We are often the first ones in the medical system to diagnose VTE, and it is quite possible to keep these patients home, thereby eliminating risks they may encounter by being hospitalized. In addition, the recommendation regarding the use of DOACs may ease some of the burden of monitoring patients on long-term Coumadin. These medications do not come without risks, and we must be comfortable evaluating for any complications. In our current health care system, different insurance companies have different formularies making it necessary for us to know all these medications.

In the past, the diagnosis of PE and even a DVT would mean a hospital stay. We now know, and these guidelines reaffirm, that this is not necessary in uncomplicated cases.

In addition to diagnosing VTE, family physicians are also tasked with following up with patients who were hospitalized or started on treatment by other physicians. We need to know the plan on when to stop the medication or when to reevaluate its use. Patients often bring this question to us, and these guidelines will help us answer that question.

Many patients who have more complicated medical conditions often see multiple specialists. The ASH recommendations help standardize the care of these patients across specialties.

What the recommendations are missing

As family doctors, we often treat patients with multiple comorbidities. These guidelines do not make recommendations for patients with cancer, who are at high risk of VTE events. Some patients also have conditions that increase their risk of bleeding or have contraindications to the use of anticoagulants. It would be helpful to have more recommendations for both of these types of patients in addition to the use of inferior vena cava filter in patients with proximal DVT. The document is also missing recommendations for pregnant patients, which would be useful.

Overall, these guidelines include much of what we already do in our practices while doing a great job of incorporating the newer DOACs. These guidelines are easy for family physicians to put into practice.
 

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].

Each year in the United States, approximately one to two out of every thousand people suffer from venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism. The American Society of Hematology (ASH) issued new guidelines for the management of VTE, including primary treatment, secondary prevention, and treatment of recurrent events, earlier this year.

These guidelines, which were recently published in Blood Advances (Ortel T L et al. Blood Adv 2020 doi: 10.1182/bloodadvances.2020001830), include 28 recommendations.

How to treat uncomplicated patients

For uncomplicated deep vein thrombosis (DVT) and/or pulmonary embolism (PE), the guidelines suggest treating patients at home rather than in the hospital. This is especially important for family physicians to note as many of these patients will now be the responsibility of the primary care doctor to treat and follow. Patients treated at home can avoid the risk of nosocomial infections, especially in the days of COVID-19. Evidence also suggests that being treated at home was shown to reduce the risk of PE versus being treated in the hospital. It is, therefore, crucial that family physicians know which patients are low versus high risk.

Further, the guidelines suggest that these patients with low risk of complications are better treated with direct oral anticoagulants (DOACs) instead of vitamin K antagonists, such as Coumadin.

Medication-related suggestions

The guidelines also suggest that no DOAC is preferred over another. Since DOACs are relatively newer agents, family doctors need to become comfortable with their use. For proximal DVTs, anticoagulation alone can be used without thrombolytics.

Family physicians are often tasked with the decision on when to stop anticoagulation. The authors recommend against using diagnostic tests such as D-Dimer or ultrasound to decide when to stop these medications in low-risk patients. In patients at risk of recurrent VTE due to chronic medical conditions, it is suggested to continue anti-coagulants indefinitely. While anticoagulant therapy effectively reduces risk of VTE, it does increase the risk of bleeding events.

The guidelines are quite extensive and specific in their recommendations and family physicians need to understand them. We are often the first ones in the medical system to diagnose VTE, and it is quite possible to keep these patients home, thereby eliminating risks they may encounter by being hospitalized. In addition, the recommendation regarding the use of DOACs may ease some of the burden of monitoring patients on long-term Coumadin. These medications do not come without risks, and we must be comfortable evaluating for any complications. In our current health care system, different insurance companies have different formularies making it necessary for us to know all these medications.

In the past, the diagnosis of PE and even a DVT would mean a hospital stay. We now know, and these guidelines reaffirm, that this is not necessary in uncomplicated cases.

In addition to diagnosing VTE, family physicians are also tasked with following up with patients who were hospitalized or started on treatment by other physicians. We need to know the plan on when to stop the medication or when to reevaluate its use. Patients often bring this question to us, and these guidelines will help us answer that question.

Many patients who have more complicated medical conditions often see multiple specialists. The ASH recommendations help standardize the care of these patients across specialties.

What the recommendations are missing

As family doctors, we often treat patients with multiple comorbidities. These guidelines do not make recommendations for patients with cancer, who are at high risk of VTE events. Some patients also have conditions that increase their risk of bleeding or have contraindications to the use of anticoagulants. It would be helpful to have more recommendations for both of these types of patients in addition to the use of inferior vena cava filter in patients with proximal DVT. The document is also missing recommendations for pregnant patients, which would be useful.

Overall, these guidelines include much of what we already do in our practices while doing a great job of incorporating the newer DOACs. These guidelines are easy for family physicians to put into practice.
 

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].

Background: Venous thromboembolism and pulmonary embolism are common after major trauma. Anticoagulant prophylaxis usually is not considered because of the increased risk of bleeding. Despite the limited data, many trauma centers use inferior vena cava (IVC) filters as a primary means to prevent pulmonary embolism.

Study design: Randomized, controlled, and multicenter trial.

Setting: Four tertiary hospitals in Australia.

Synopsis: 240 major trauma patients were randomly assigned to receive either IVC filter or no IVC filter within 72 hours after admission. The primary endpoint was a composite of 90-day mortality or symptomatic pulmonary embolism confirmed on imaging. There was no difference in the rate of composite outcome in those with IVC filter, compared with those with no IVC filter.

Bottom line: After major trauma, early prophylactic placement of IVC filter did not reduce the 90-day mortality or incidence of symptomatic pulmonary embolism.

Citation: Ho KM et al. A multicenter trial of vena cava filters in severely injured patients. N Engl J Med. 2019 Jul 25;381:328-37.

Dr. Hoque Sharmy is a hospitalist and assistant professor of medicine in the division of hospital medicine at St. Louis University School of Medicine.

Background: Venous thromboembolism and pulmonary embolism are common after major trauma. Anticoagulant prophylaxis usually is not considered because of the increased risk of bleeding. Despite the limited data, many trauma centers use inferior vena cava (IVC) filters as a primary means to prevent pulmonary embolism.

Study design: Randomized, controlled, and multicenter trial.

Setting: Four tertiary hospitals in Australia.

Synopsis: 240 major trauma patients were randomly assigned to receive either IVC filter or no IVC filter within 72 hours after admission. The primary endpoint was a composite of 90-day mortality or symptomatic pulmonary embolism confirmed on imaging. There was no difference in the rate of composite outcome in those with IVC filter, compared with those with no IVC filter.

Bottom line: After major trauma, early prophylactic placement of IVC filter did not reduce the 90-day mortality or incidence of symptomatic pulmonary embolism.

Citation: Ho KM et al. A multicenter trial of vena cava filters in severely injured patients. N Engl J Med. 2019 Jul 25;381:328-37.

Dr. Hoque Sharmy is a hospitalist and assistant professor of medicine in the division of hospital medicine at St. Louis University School of Medicine.

Background: Venous thromboembolism and pulmonary embolism are common after major trauma. Anticoagulant prophylaxis usually is not considered because of the increased risk of bleeding. Despite the limited data, many trauma centers use inferior vena cava (IVC) filters as a primary means to prevent pulmonary embolism.

Study design: Randomized, controlled, and multicenter trial.

Setting: Four tertiary hospitals in Australia.

Synopsis: 240 major trauma patients were randomly assigned to receive either IVC filter or no IVC filter within 72 hours after admission. The primary endpoint was a composite of 90-day mortality or symptomatic pulmonary embolism confirmed on imaging. There was no difference in the rate of composite outcome in those with IVC filter, compared with those with no IVC filter.

Bottom line: After major trauma, early prophylactic placement of IVC filter did not reduce the 90-day mortality or incidence of symptomatic pulmonary embolism.

Citation: Ho KM et al. A multicenter trial of vena cava filters in severely injured patients. N Engl J Med. 2019 Jul 25;381:328-37.

Dr. Hoque Sharmy is a hospitalist and assistant professor of medicine in the division of hospital medicine at St. Louis University School of Medicine.