Anticoagulation Hub

CHICAGO – Once-daily, low-dose aspirin failed to reduce the combined outcome of cardiovascular death, nonfatal stroke, and nonfatal MI in elderly Japanese patients with atherosclerotic risk factors in the JPPP study.

The cumulative rate of the composite primary outcome was 2.77% with 100 mg/day of aspirin and 2.96% with no aspirin (HR, 0.94; P = .54), Dr. Kazuyuki Shimada reported at the American Heart Association scientific sessions.

However, patients randomized to aspirin did have reductions of 47% and 43% in the individual endpoints of nonfatal MI and transient ischemic attack, respectively.

These benefits had to be weighed against an 85% increase in serious extracranial hemorrhage in those on aspirin, according to results of the Japanese Primary Prevention Project (JPPP), simultaneously published online in JAMA (doi:10.1001/jama.2014.15690).

How generalizable are these results, and is this the end of the road for aspirin in primary prevention? We asked several experts, including invited discussant Dr. Dorairaj Prabhakaran of the Public Health Foundation of India, Dr. Karol Watson of the UCLA Center for Cholesterol and Lipid Management, and Dr. Donald Lloyd-Jonesof Northwestern University in Chicago.

The study was sponsored by the Japanese Ministry of Health, Labor, and Welfare, and the Waksman Foundation of Japan. Bayer Yakuhin provided the aspirin. Dr. Shimada reported honorarium from MSD, Shionogi, Takeda, Daiichi-Sankyo, and Dainippon-Sumitomo, and serving as a consultant/advisory board member for Omron.

Dr. Prabhakaran and Dr. Jones reported no conflicting interests. Dr. Watson reported participating in the clinical trials adjudication committee for Merck.

[email protected]

CHICAGO – Once-daily, low-dose aspirin failed to reduce the combined outcome of cardiovascular death, nonfatal stroke, and nonfatal MI in elderly Japanese patients with atherosclerotic risk factors in the JPPP study.

The cumulative rate of the composite primary outcome was 2.77% with 100 mg/day of aspirin and 2.96% with no aspirin (HR, 0.94; P = .54), Dr. Kazuyuki Shimada reported at the American Heart Association scientific sessions.

However, patients randomized to aspirin did have reductions of 47% and 43% in the individual endpoints of nonfatal MI and transient ischemic attack, respectively.

These benefits had to be weighed against an 85% increase in serious extracranial hemorrhage in those on aspirin, according to results of the Japanese Primary Prevention Project (JPPP), simultaneously published online in JAMA (doi:10.1001/jama.2014.15690).

How generalizable are these results, and is this the end of the road for aspirin in primary prevention? We asked several experts, including invited discussant Dr. Dorairaj Prabhakaran of the Public Health Foundation of India, Dr. Karol Watson of the UCLA Center for Cholesterol and Lipid Management, and Dr. Donald Lloyd-Jonesof Northwestern University in Chicago.

The study was sponsored by the Japanese Ministry of Health, Labor, and Welfare, and the Waksman Foundation of Japan. Bayer Yakuhin provided the aspirin. Dr. Shimada reported honorarium from MSD, Shionogi, Takeda, Daiichi-Sankyo, and Dainippon-Sumitomo, and serving as a consultant/advisory board member for Omron.

Dr. Prabhakaran and Dr. Jones reported no conflicting interests. Dr. Watson reported participating in the clinical trials adjudication committee for Merck.

[email protected]

CHICAGO – Once-daily, low-dose aspirin failed to reduce the combined outcome of cardiovascular death, nonfatal stroke, and nonfatal MI in elderly Japanese patients with atherosclerotic risk factors in the JPPP study.

The cumulative rate of the composite primary outcome was 2.77% with 100 mg/day of aspirin and 2.96% with no aspirin (HR, 0.94; P = .54), Dr. Kazuyuki Shimada reported at the American Heart Association scientific sessions.

However, patients randomized to aspirin did have reductions of 47% and 43% in the individual endpoints of nonfatal MI and transient ischemic attack, respectively.

These benefits had to be weighed against an 85% increase in serious extracranial hemorrhage in those on aspirin, according to results of the Japanese Primary Prevention Project (JPPP), simultaneously published online in JAMA (doi:10.1001/jama.2014.15690).

How generalizable are these results, and is this the end of the road for aspirin in primary prevention? We asked several experts, including invited discussant Dr. Dorairaj Prabhakaran of the Public Health Foundation of India, Dr. Karol Watson of the UCLA Center for Cholesterol and Lipid Management, and Dr. Donald Lloyd-Jonesof Northwestern University in Chicago.

The study was sponsored by the Japanese Ministry of Health, Labor, and Welfare, and the Waksman Foundation of Japan. Bayer Yakuhin provided the aspirin. Dr. Shimada reported honorarium from MSD, Shionogi, Takeda, Daiichi-Sankyo, and Dainippon-Sumitomo, and serving as a consultant/advisory board member for Omron.

Dr. Prabhakaran and Dr. Jones reported no conflicting interests. Dr. Watson reported participating in the clinical trials adjudication committee for Merck.

[email protected]

AUSTIN, TEX. – Extended treatment with any of the novel oral anticoagulants, but with apixaban in particular, provides a net clinical benefit in patients at risk of recurrent venous thromboembolism, according to a review of three randomized trials.

Apixaban appears to provide the optimal net clinical benefit, with the lowest number needed to treat to avoid one venous thromboembolic or major bleeding event, Dr. Alpesh Amin reported at the annual meeting of the American College of Chest Physicians.

In 5,035 patients in three trials of extended treatment with novel oral anticoagulants (NOACs) for venous thromboembolism (VTE) – including the RE-SONATE trial, the EINSTEIN-EXT trial, and the AMPLIFY-EXT trial – the differences in event rates, compared with placebo, were –5.15% for dabigatran, –5.74% for rivaroxaban, –7.14% for 2.5 mg apixaban, and –7.0% for 5 mg apixaban, reported Dr. Amin of the University of California, Irvine.

The number needed to treat to avoid one VTE or major bleeding event was 21 for dabigatran, 20 for rivaroxaban, 14 for 2.5 mg apixaban, and 13 for 5 mg apixaban, Dr. Amin said.

“The good news is that the number needed to treat for all of [the oral anticoagulants] is actually less than 25,” he said.

As for costs, the savings from avoiding a recurrent VTE were $2,995 with dabigatran, $3,300 for rivaroxaban, and $4,100 for both 2.5 and 5 mg apixaban.

For major bleeding events, the corresponding rates, compared with placebo, were 0.29%, 0.67%, –0.20%, and –0.36%.

There was a net clinical benefit for all patients treated with the NOACs, but in those treated with 5 mg apixaban, the rates of improvement were highest at –7.44%, followed by –7.38% for 2.5 mg apixaban. The rates were –5.0% with rivaroxaban and –4.85% with dabigatran.

“So we see a low number needed to treat, and a significant amount of cost avoidance by using the NOACs across the board,” he said, adding that apixaban may provide the best net clinical benefit for the lowest number needed to treat to avoid one VTE or major bleeding event, and is associated with the greatest medical cost avoidance.

“In terms of safety endpoints, dabigatran and rivaroxaban cost the system a little bit of money, whereas apixaban actually decreased the cost,” he said.

“How these results translate into real-world outcomes will require further evaluation, and as we get more numbers out there, we will actually be looking at the impact in the real world,” he said.

Dr. Amin reported serving as a paid consultant and/or member of a speakers bureau or advisory committee for Bristol-Myers Squibb and Pfizer.

AUSTIN, TEX. – Extended treatment with any of the novel oral anticoagulants, but with apixaban in particular, provides a net clinical benefit in patients at risk of recurrent venous thromboembolism, according to a review of three randomized trials.

Apixaban appears to provide the optimal net clinical benefit, with the lowest number needed to treat to avoid one venous thromboembolic or major bleeding event, Dr. Alpesh Amin reported at the annual meeting of the American College of Chest Physicians.

In 5,035 patients in three trials of extended treatment with novel oral anticoagulants (NOACs) for venous thromboembolism (VTE) – including the RE-SONATE trial, the EINSTEIN-EXT trial, and the AMPLIFY-EXT trial – the differences in event rates, compared with placebo, were –5.15% for dabigatran, –5.74% for rivaroxaban, –7.14% for 2.5 mg apixaban, and –7.0% for 5 mg apixaban, reported Dr. Amin of the University of California, Irvine.

The number needed to treat to avoid one VTE or major bleeding event was 21 for dabigatran, 20 for rivaroxaban, 14 for 2.5 mg apixaban, and 13 for 5 mg apixaban, Dr. Amin said.

“The good news is that the number needed to treat for all of [the oral anticoagulants] is actually less than 25,” he said.

As for costs, the savings from avoiding a recurrent VTE were $2,995 with dabigatran, $3,300 for rivaroxaban, and $4,100 for both 2.5 and 5 mg apixaban.

For major bleeding events, the corresponding rates, compared with placebo, were 0.29%, 0.67%, –0.20%, and –0.36%.

There was a net clinical benefit for all patients treated with the NOACs, but in those treated with 5 mg apixaban, the rates of improvement were highest at –7.44%, followed by –7.38% for 2.5 mg apixaban. The rates were –5.0% with rivaroxaban and –4.85% with dabigatran.

“So we see a low number needed to treat, and a significant amount of cost avoidance by using the NOACs across the board,” he said, adding that apixaban may provide the best net clinical benefit for the lowest number needed to treat to avoid one VTE or major bleeding event, and is associated with the greatest medical cost avoidance.

“In terms of safety endpoints, dabigatran and rivaroxaban cost the system a little bit of money, whereas apixaban actually decreased the cost,” he said.

“How these results translate into real-world outcomes will require further evaluation, and as we get more numbers out there, we will actually be looking at the impact in the real world,” he said.

Dr. Amin reported serving as a paid consultant and/or member of a speakers bureau or advisory committee for Bristol-Myers Squibb and Pfizer.

AUSTIN, TEX. – Extended treatment with any of the novel oral anticoagulants, but with apixaban in particular, provides a net clinical benefit in patients at risk of recurrent venous thromboembolism, according to a review of three randomized trials.

Apixaban appears to provide the optimal net clinical benefit, with the lowest number needed to treat to avoid one venous thromboembolic or major bleeding event, Dr. Alpesh Amin reported at the annual meeting of the American College of Chest Physicians.

In 5,035 patients in three trials of extended treatment with novel oral anticoagulants (NOACs) for venous thromboembolism (VTE) – including the RE-SONATE trial, the EINSTEIN-EXT trial, and the AMPLIFY-EXT trial – the differences in event rates, compared with placebo, were –5.15% for dabigatran, –5.74% for rivaroxaban, –7.14% for 2.5 mg apixaban, and –7.0% for 5 mg apixaban, reported Dr. Amin of the University of California, Irvine.

The number needed to treat to avoid one VTE or major bleeding event was 21 for dabigatran, 20 for rivaroxaban, 14 for 2.5 mg apixaban, and 13 for 5 mg apixaban, Dr. Amin said.

“The good news is that the number needed to treat for all of [the oral anticoagulants] is actually less than 25,” he said.

As for costs, the savings from avoiding a recurrent VTE were $2,995 with dabigatran, $3,300 for rivaroxaban, and $4,100 for both 2.5 and 5 mg apixaban.

For major bleeding events, the corresponding rates, compared with placebo, were 0.29%, 0.67%, –0.20%, and –0.36%.

There was a net clinical benefit for all patients treated with the NOACs, but in those treated with 5 mg apixaban, the rates of improvement were highest at –7.44%, followed by –7.38% for 2.5 mg apixaban. The rates were –5.0% with rivaroxaban and –4.85% with dabigatran.

“So we see a low number needed to treat, and a significant amount of cost avoidance by using the NOACs across the board,” he said, adding that apixaban may provide the best net clinical benefit for the lowest number needed to treat to avoid one VTE or major bleeding event, and is associated with the greatest medical cost avoidance.

“In terms of safety endpoints, dabigatran and rivaroxaban cost the system a little bit of money, whereas apixaban actually decreased the cost,” he said.

“How these results translate into real-world outcomes will require further evaluation, and as we get more numbers out there, we will actually be looking at the impact in the real world,” he said.

Dr. Amin reported serving as a paid consultant and/or member of a speakers bureau or advisory committee for Bristol-Myers Squibb and Pfizer.

Atrial fibrillation is associated with a more than twofold increase in the risk of silent cerebral infarctions, even in patients with no history of symptomatic stroke, a systematic review and meta-analysis has found.

The analysis of 11 studies involving 5,317 adults with atrial fibrillation (AF) but no history of stroke or prosthetic valves showed a significant increase in the risk of silent cerebral infarctions (odds ratio, 2.62), independent of whether their atrial fibrillation was paroxysmal or persistent, according to meta-analysis published online Nov. 3 in the Annals of Internal Medicine [doi:10.7326/M14-0538].

“Although SCIs [silent cerebral infarctions] do not present with acute stroke symptoms, they have been reported to be associated with more than three- and twofold increases in the risk for symptomatic stroke and dementia, respectively,” wrote Dr. Shadi Kalantarian and colleagues from the Institute for Heart Vascular and Stroke Care and Massachusetts General Hospital.

“Consequently, the higher prevalence of SCI in patients with AF may put this population at a greater risk for cognitive impairment, future stroke, and disability.”

The study was funded by the Deane Institute for Integrative Research in Atrial Fibrillation and Stroke, Massachusetts General Hospital, and the Harvard Catalyst and the Harvard Clinical and Translational Science Center. Two authors declared grants and personal fees from private industry.

Atrial fibrillation is associated with a more than twofold increase in the risk of silent cerebral infarctions, even in patients with no history of symptomatic stroke, a systematic review and meta-analysis has found.

The analysis of 11 studies involving 5,317 adults with atrial fibrillation (AF) but no history of stroke or prosthetic valves showed a significant increase in the risk of silent cerebral infarctions (odds ratio, 2.62), independent of whether their atrial fibrillation was paroxysmal or persistent, according to meta-analysis published online Nov. 3 in the Annals of Internal Medicine [doi:10.7326/M14-0538].

“Although SCIs [silent cerebral infarctions] do not present with acute stroke symptoms, they have been reported to be associated with more than three- and twofold increases in the risk for symptomatic stroke and dementia, respectively,” wrote Dr. Shadi Kalantarian and colleagues from the Institute for Heart Vascular and Stroke Care and Massachusetts General Hospital.

“Consequently, the higher prevalence of SCI in patients with AF may put this population at a greater risk for cognitive impairment, future stroke, and disability.”

The study was funded by the Deane Institute for Integrative Research in Atrial Fibrillation and Stroke, Massachusetts General Hospital, and the Harvard Catalyst and the Harvard Clinical and Translational Science Center. Two authors declared grants and personal fees from private industry.

Atrial fibrillation is associated with a more than twofold increase in the risk of silent cerebral infarctions, even in patients with no history of symptomatic stroke, a systematic review and meta-analysis has found.

The analysis of 11 studies involving 5,317 adults with atrial fibrillation (AF) but no history of stroke or prosthetic valves showed a significant increase in the risk of silent cerebral infarctions (odds ratio, 2.62), independent of whether their atrial fibrillation was paroxysmal or persistent, according to meta-analysis published online Nov. 3 in the Annals of Internal Medicine [doi:10.7326/M14-0538].

“Although SCIs [silent cerebral infarctions] do not present with acute stroke symptoms, they have been reported to be associated with more than three- and twofold increases in the risk for symptomatic stroke and dementia, respectively,” wrote Dr. Shadi Kalantarian and colleagues from the Institute for Heart Vascular and Stroke Care and Massachusetts General Hospital.

“Consequently, the higher prevalence of SCI in patients with AF may put this population at a greater risk for cognitive impairment, future stroke, and disability.”

The study was funded by the Deane Institute for Integrative Research in Atrial Fibrillation and Stroke, Massachusetts General Hospital, and the Harvard Catalyst and the Harvard Clinical and Translational Science Center. Two authors declared grants and personal fees from private industry.

Dabigatran significantly raises the risk of major bleeding and gastrointestinal bleeding across all subgroups of patients with atrial fibrillation, and particularly in African Americans and patients with chronic kidney disease, according to a report published online Nov. 3 in JAMA Internal Medicine.

Physicians should only prescribe dabigatran with caution, and should fully explain to patients who do take the drug how to identify abnormal bleeding so that it can be detected and controlled as early as possible, said Inmaculada Hernandez, Pharm.D., of the department of health policy and management, University of Pittsburgh, and her associates.

The FDA approved dabigatran in 2010 via an accelerated pathway after only 6 months of review, based largely on findings from a single clinical study, the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial, which did not adjust for patient characteristics (N. Engl. J. Med. 2009;361:1139-51). That study reported lower bleeding risks with dabigatran than with warfarin. Several months later, the agency’s Adverse Event Reporting System received “a large number” of reports of severe bleeding associated with dabigatran; and the relative bleeding risk associated with the two drugs is still unclear.

Dr. Hernandez and her colleagues examined the issue using data from a nationally representative random sample of 9,404 Medicare beneficiaries newly diagnosed as having nonvalvular atrial fibrillation during a 1-year period and treated in real-world practice. A total of 1,302 patients were given dabigatran and 8,102 were given warfarin to prevent stroke and systemic embolism. They were followed for a median of about 200 days, until discontinuing or switching their anticoagulant, dying, or reaching the study’s cutoff date. Nine categories of bleeding were assessed, and the data were adjusted to account for numerous demographic and clinical characteristics known to affect bleeding risk.

Compared with warfarin, dabigatran was associated with a significantly higher risk of major bleeding (9.0% vs 5.9%), with a hazard ratio of 1.58. Dabigatran also was associated with a significantly higher risk of GI bleeding (HR, 1.85), hematuria (HR, 1.41), vaginal bleeding (HR, 2.27), hemarthrosis (HR, 2.78), and hemoptysis (HR, 1.49). In contrast, dabigatran was associated with a slightly lower (0.6%) rate of intracranial bleeding, and also with lower rates of epistaxis and nonspecified bleeding, the investigators reported (JAMA Intern. Med. 2014 Nov. 3 [doi: 10.1001/jamainternmed.2014.5398]).

These differences were consistent across numerous subgroups of patients assessed, and were especially strong among African Americans and patients with chronic kidney disease.

This study was supported by the Commonwealth Foundation and the U.S. Agency for Healthcare Research and Quality. Dr. Hernandez and her associates reported having no financial conflicts of interest.

Dabigatran significantly raises the risk of major bleeding and gastrointestinal bleeding across all subgroups of patients with atrial fibrillation, and particularly in African Americans and patients with chronic kidney disease, according to a report published online Nov. 3 in JAMA Internal Medicine.

Physicians should only prescribe dabigatran with caution, and should fully explain to patients who do take the drug how to identify abnormal bleeding so that it can be detected and controlled as early as possible, said Inmaculada Hernandez, Pharm.D., of the department of health policy and management, University of Pittsburgh, and her associates.

The FDA approved dabigatran in 2010 via an accelerated pathway after only 6 months of review, based largely on findings from a single clinical study, the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial, which did not adjust for patient characteristics (N. Engl. J. Med. 2009;361:1139-51). That study reported lower bleeding risks with dabigatran than with warfarin. Several months later, the agency’s Adverse Event Reporting System received “a large number” of reports of severe bleeding associated with dabigatran; and the relative bleeding risk associated with the two drugs is still unclear.

Dr. Hernandez and her colleagues examined the issue using data from a nationally representative random sample of 9,404 Medicare beneficiaries newly diagnosed as having nonvalvular atrial fibrillation during a 1-year period and treated in real-world practice. A total of 1,302 patients were given dabigatran and 8,102 were given warfarin to prevent stroke and systemic embolism. They were followed for a median of about 200 days, until discontinuing or switching their anticoagulant, dying, or reaching the study’s cutoff date. Nine categories of bleeding were assessed, and the data were adjusted to account for numerous demographic and clinical characteristics known to affect bleeding risk.

Compared with warfarin, dabigatran was associated with a significantly higher risk of major bleeding (9.0% vs 5.9%), with a hazard ratio of 1.58. Dabigatran also was associated with a significantly higher risk of GI bleeding (HR, 1.85), hematuria (HR, 1.41), vaginal bleeding (HR, 2.27), hemarthrosis (HR, 2.78), and hemoptysis (HR, 1.49). In contrast, dabigatran was associated with a slightly lower (0.6%) rate of intracranial bleeding, and also with lower rates of epistaxis and nonspecified bleeding, the investigators reported (JAMA Intern. Med. 2014 Nov. 3 [doi: 10.1001/jamainternmed.2014.5398]).

These differences were consistent across numerous subgroups of patients assessed, and were especially strong among African Americans and patients with chronic kidney disease.

This study was supported by the Commonwealth Foundation and the U.S. Agency for Healthcare Research and Quality. Dr. Hernandez and her associates reported having no financial conflicts of interest.

Dabigatran significantly raises the risk of major bleeding and gastrointestinal bleeding across all subgroups of patients with atrial fibrillation, and particularly in African Americans and patients with chronic kidney disease, according to a report published online Nov. 3 in JAMA Internal Medicine.

Physicians should only prescribe dabigatran with caution, and should fully explain to patients who do take the drug how to identify abnormal bleeding so that it can be detected and controlled as early as possible, said Inmaculada Hernandez, Pharm.D., of the department of health policy and management, University of Pittsburgh, and her associates.

The FDA approved dabigatran in 2010 via an accelerated pathway after only 6 months of review, based largely on findings from a single clinical study, the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial, which did not adjust for patient characteristics (N. Engl. J. Med. 2009;361:1139-51). That study reported lower bleeding risks with dabigatran than with warfarin. Several months later, the agency’s Adverse Event Reporting System received “a large number” of reports of severe bleeding associated with dabigatran; and the relative bleeding risk associated with the two drugs is still unclear.

Dr. Hernandez and her colleagues examined the issue using data from a nationally representative random sample of 9,404 Medicare beneficiaries newly diagnosed as having nonvalvular atrial fibrillation during a 1-year period and treated in real-world practice. A total of 1,302 patients were given dabigatran and 8,102 were given warfarin to prevent stroke and systemic embolism. They were followed for a median of about 200 days, until discontinuing or switching their anticoagulant, dying, or reaching the study’s cutoff date. Nine categories of bleeding were assessed, and the data were adjusted to account for numerous demographic and clinical characteristics known to affect bleeding risk.

Compared with warfarin, dabigatran was associated with a significantly higher risk of major bleeding (9.0% vs 5.9%), with a hazard ratio of 1.58. Dabigatran also was associated with a significantly higher risk of GI bleeding (HR, 1.85), hematuria (HR, 1.41), vaginal bleeding (HR, 2.27), hemarthrosis (HR, 2.78), and hemoptysis (HR, 1.49). In contrast, dabigatran was associated with a slightly lower (0.6%) rate of intracranial bleeding, and also with lower rates of epistaxis and nonspecified bleeding, the investigators reported (JAMA Intern. Med. 2014 Nov. 3 [doi: 10.1001/jamainternmed.2014.5398]).

These differences were consistent across numerous subgroups of patients assessed, and were especially strong among African Americans and patients with chronic kidney disease.

This study was supported by the Commonwealth Foundation and the U.S. Agency for Healthcare Research and Quality. Dr. Hernandez and her associates reported having no financial conflicts of interest.

The low molecular weight heparin dalteparin and unfractionated heparin are associated with similar rates of thrombosis and major bleeding, but dalteparin is associated with lower rates of pulmonary embolus and heparin-induced thrombocytopenia, based on results from a prospective randomized study.

Given for prevention of venous thromboembolism, median hospital costs per patient were $39,508 for dalteparin users and $40,805 for unfractionated heparin users. Dalteparin remained the least costly strategy until its acquisition costs rose from $8 per dose to $179, as reported online 1 November in the Journal of the American Medical Association [doi:10.1001/jama.2014.15101].

CDC/Janice Carr

The economic analysis—conducted alongside the multi-centre, randomized PROTECT trial in 2344 critically-ill medical-surgical patients— showed no matter how low the acquisition cost of unfractionated heparin, there was no threshold that favored that form of prophylaxis, according to data also presented at the Critical Care Canada Forum.

“From a health care payer perspective, VTE prophylaxis with the LMWH [low molecular weight heparin] dalteparin in critically ill medical-surgical patients was more effective and had similar or lower costs than the use of UFH [unfractionated heparin],” wrote Dr. Robert A. Fowler, from the Sunnybrook Health Sciences Centre, University of Toronto, and colleagues.The E-PROTECT study was funded by the Heart and Stroke Foundation (Ontario, Canada), the University of Toronto, and the Canadian Intensive Care Foundation. PROTECT was funded by the Canadian Institutes of Health Research, the Heart and Stroke Foundation (Canada), and the Australian and New Zealand College of Anesthetists Research Foundation. Some authors reported fees, support, and consultancies from the pharmaceutical industry.

The low molecular weight heparin dalteparin and unfractionated heparin are associated with similar rates of thrombosis and major bleeding, but dalteparin is associated with lower rates of pulmonary embolus and heparin-induced thrombocytopenia, based on results from a prospective randomized study.

Given for prevention of venous thromboembolism, median hospital costs per patient were $39,508 for dalteparin users and $40,805 for unfractionated heparin users. Dalteparin remained the least costly strategy until its acquisition costs rose from $8 per dose to $179, as reported online 1 November in the Journal of the American Medical Association [doi:10.1001/jama.2014.15101].

CDC/Janice Carr

The economic analysis—conducted alongside the multi-centre, randomized PROTECT trial in 2344 critically-ill medical-surgical patients— showed no matter how low the acquisition cost of unfractionated heparin, there was no threshold that favored that form of prophylaxis, according to data also presented at the Critical Care Canada Forum.

“From a health care payer perspective, VTE prophylaxis with the LMWH [low molecular weight heparin] dalteparin in critically ill medical-surgical patients was more effective and had similar or lower costs than the use of UFH [unfractionated heparin],” wrote Dr. Robert A. Fowler, from the Sunnybrook Health Sciences Centre, University of Toronto, and colleagues.The E-PROTECT study was funded by the Heart and Stroke Foundation (Ontario, Canada), the University of Toronto, and the Canadian Intensive Care Foundation. PROTECT was funded by the Canadian Institutes of Health Research, the Heart and Stroke Foundation (Canada), and the Australian and New Zealand College of Anesthetists Research Foundation. Some authors reported fees, support, and consultancies from the pharmaceutical industry.

The low molecular weight heparin dalteparin and unfractionated heparin are associated with similar rates of thrombosis and major bleeding, but dalteparin is associated with lower rates of pulmonary embolus and heparin-induced thrombocytopenia, based on results from a prospective randomized study.

Given for prevention of venous thromboembolism, median hospital costs per patient were $39,508 for dalteparin users and $40,805 for unfractionated heparin users. Dalteparin remained the least costly strategy until its acquisition costs rose from $8 per dose to $179, as reported online 1 November in the Journal of the American Medical Association [doi:10.1001/jama.2014.15101].

CDC/Janice Carr

The economic analysis—conducted alongside the multi-centre, randomized PROTECT trial in 2344 critically-ill medical-surgical patients— showed no matter how low the acquisition cost of unfractionated heparin, there was no threshold that favored that form of prophylaxis, according to data also presented at the Critical Care Canada Forum.

“From a health care payer perspective, VTE prophylaxis with the LMWH [low molecular weight heparin] dalteparin in critically ill medical-surgical patients was more effective and had similar or lower costs than the use of UFH [unfractionated heparin],” wrote Dr. Robert A. Fowler, from the Sunnybrook Health Sciences Centre, University of Toronto, and colleagues.The E-PROTECT study was funded by the Heart and Stroke Foundation (Ontario, Canada), the University of Toronto, and the Canadian Intensive Care Foundation. PROTECT was funded by the Canadian Institutes of Health Research, the Heart and Stroke Foundation (Canada), and the Australian and New Zealand College of Anesthetists Research Foundation. Some authors reported fees, support, and consultancies from the pharmaceutical industry.

AUSTIN, TEX.– Genetic testing holds promise for guiding the prescribing of antiplatelet therapies, particularly clopidogrel, but “we’re not there yet,” according to Dr. Steven Hollenberg, director of the coronary care unit at Cooper University Hospital in Camden, N.J.Genetic testing for clopidogrel responsiveness “certainly makes good sense, but I think we’re going to have to wait for good data” that better informs clinical decision making.Dr. Hollenberg discussed the implications of the negative results of the ARCTIC trial, which showed platelet function testing with antiplatelet therapy adjustment failed to improve clinical outcomes compared with standard unmonitored thienopyridine therapy in elective PCI. He also analyzed the results of other studies relevant to optimal antiplatelet and anticoagulant therapy, including the surprising outcomes of the WOEST trial.

[email protected]

On Twitter @whitneymcknight

AUSTIN, TEX.– Genetic testing holds promise for guiding the prescribing of antiplatelet therapies, particularly clopidogrel, but “we’re not there yet,” according to Dr. Steven Hollenberg, director of the coronary care unit at Cooper University Hospital in Camden, N.J.Genetic testing for clopidogrel responsiveness “certainly makes good sense, but I think we’re going to have to wait for good data” that better informs clinical decision making.Dr. Hollenberg discussed the implications of the negative results of the ARCTIC trial, which showed platelet function testing with antiplatelet therapy adjustment failed to improve clinical outcomes compared with standard unmonitored thienopyridine therapy in elective PCI. He also analyzed the results of other studies relevant to optimal antiplatelet and anticoagulant therapy, including the surprising outcomes of the WOEST trial.

[email protected]

On Twitter @whitneymcknight

AUSTIN, TEX.– Genetic testing holds promise for guiding the prescribing of antiplatelet therapies, particularly clopidogrel, but “we’re not there yet,” according to Dr. Steven Hollenberg, director of the coronary care unit at Cooper University Hospital in Camden, N.J.Genetic testing for clopidogrel responsiveness “certainly makes good sense, but I think we’re going to have to wait for good data” that better informs clinical decision making.Dr. Hollenberg discussed the implications of the negative results of the ARCTIC trial, which showed platelet function testing with antiplatelet therapy adjustment failed to improve clinical outcomes compared with standard unmonitored thienopyridine therapy in elective PCI. He also analyzed the results of other studies relevant to optimal antiplatelet and anticoagulant therapy, including the surprising outcomes of the WOEST trial.

[email protected]

On Twitter @whitneymcknight

PHILADELPHIA – Dabigatran and rivaroxaban, which are rapidly replacing warfarin for anticoagulation in patients with atrial fibrillation, appear to be associated with a greater risk of GI bleeding than the long-time standard in patients over the age of 65 years, according to an analysis presented at the American College of Gastroenterology (ACG).

The pattern of an increased GI bleeding risk with the newer oral anticoagulants relative to warfarin was consistent in older patients whether used for AF or for out-of-labeling indications, which were assessed separately, reported Dr. Neena S. Abraham, professor of medicine at Mayo Clinic, Scottsdale, Ariz.

“In all four cases, once patients were over the age of 65, the risk of GI bleeding increased significantly on the novel agents when compared to warfarin,” Dr. Abraham reported.

The propensity matches, based on such characteristics as GI bleeding risk factors, age, race, and concomitant medications, were drawn from 92,816 patients in a large database starting a new prescription of dabigatran, rivaroxaban, or warfarin over a recent 3-year period. With this matching, 9,860 new users of dabigatran and 20,619 new users of rivaroxaban were compared with equal number of new users of warfarin.

In the full dataset, before age stratification, the risk of total GI bleeding, particularly lower GI bleeding, appeared to be nonsignificantly lower for both dabigatran and rivaroxaban, relative to warfarin in patients with AF. In patients without AF receiving these drugs, the risk remained slightly lower on rivaroxaban but appeared to be slightly increased on dabigatran.

However, the hypothesis that bleeding risk was greater for newer agents in older patients was substantiated when the data were stratified by age. In the analysis, risk of bleeding started climbing more steeply with the newer agents as patients aged than with warfarin, with differences observed at about age 65 years.

By age 75, the hazard ratio for a GI bleed in dabigatran patients relative to warfarin in AF patients was 2.4 (95% confidence interval 1.5-3.8). In the rivaroxaban group, the HR for this risk at age 75 in AF patients was 4.0 (95% CI 2.1-7.4). In non-AF patients, the rates of GI bleeding were also significantly increased at a similar magnitude.

These data were anticipated by the initial trials that found dabigatran and rivaroxaban noninferior to warfarin for the prevention of stroke and systemic embolism, according to Dr. Abraham. Although there was heterogeneity in reported risk differences, she reported that GI bleeding was as much as 25% higher on the newer anticoagulants when compared to warfarin in older patients. These new data substantiate those findings.

“Our study is the first to evaluate GI safety in novel oral anticoagulants compared to warfarin in a real-world, multiage setting,” Dr. Abraham noted. She said these data “facilitate risk-benefit considerations” of these drugs. She further noted that the data on non-AF patients may be particularly pertinent “because this is the fastest-growing emerging market” for agents in this class.

Asked for a comment, Dr. Brian E. Lacy, chief of gastroenterology and hepatology at Dartmouth-Hitchcock Medical Center, Lebanon, N.H., said that the information about relative risk is potentially important, but he was particularly impressed by the substantial use of novel anticoagulants in non-AF patients.

“This tells me that we as gastroenterologists need to be asking more questions about exposure to anticoagulants,” Dr. Lacy said in an interview. “These data suggest that these newer drugs are being used frequently outside of labeling. We need to be aware of these changing patterns of use when trying to assess the risk of our patients for GI bleeds.”

Dr. Abraham had no financial disclosures.

PHILADELPHIA – Dabigatran and rivaroxaban, which are rapidly replacing warfarin for anticoagulation in patients with atrial fibrillation, appear to be associated with a greater risk of GI bleeding than the long-time standard in patients over the age of 65 years, according to an analysis presented at the American College of Gastroenterology (ACG).

The pattern of an increased GI bleeding risk with the newer oral anticoagulants relative to warfarin was consistent in older patients whether used for AF or for out-of-labeling indications, which were assessed separately, reported Dr. Neena S. Abraham, professor of medicine at Mayo Clinic, Scottsdale, Ariz.

“In all four cases, once patients were over the age of 65, the risk of GI bleeding increased significantly on the novel agents when compared to warfarin,” Dr. Abraham reported.

The propensity matches, based on such characteristics as GI bleeding risk factors, age, race, and concomitant medications, were drawn from 92,816 patients in a large database starting a new prescription of dabigatran, rivaroxaban, or warfarin over a recent 3-year period. With this matching, 9,860 new users of dabigatran and 20,619 new users of rivaroxaban were compared with equal number of new users of warfarin.

In the full dataset, before age stratification, the risk of total GI bleeding, particularly lower GI bleeding, appeared to be nonsignificantly lower for both dabigatran and rivaroxaban, relative to warfarin in patients with AF. In patients without AF receiving these drugs, the risk remained slightly lower on rivaroxaban but appeared to be slightly increased on dabigatran.

However, the hypothesis that bleeding risk was greater for newer agents in older patients was substantiated when the data were stratified by age. In the analysis, risk of bleeding started climbing more steeply with the newer agents as patients aged than with warfarin, with differences observed at about age 65 years.

By age 75, the hazard ratio for a GI bleed in dabigatran patients relative to warfarin in AF patients was 2.4 (95% confidence interval 1.5-3.8). In the rivaroxaban group, the HR for this risk at age 75 in AF patients was 4.0 (95% CI 2.1-7.4). In non-AF patients, the rates of GI bleeding were also significantly increased at a similar magnitude.

These data were anticipated by the initial trials that found dabigatran and rivaroxaban noninferior to warfarin for the prevention of stroke and systemic embolism, according to Dr. Abraham. Although there was heterogeneity in reported risk differences, she reported that GI bleeding was as much as 25% higher on the newer anticoagulants when compared to warfarin in older patients. These new data substantiate those findings.

“Our study is the first to evaluate GI safety in novel oral anticoagulants compared to warfarin in a real-world, multiage setting,” Dr. Abraham noted. She said these data “facilitate risk-benefit considerations” of these drugs. She further noted that the data on non-AF patients may be particularly pertinent “because this is the fastest-growing emerging market” for agents in this class.

Asked for a comment, Dr. Brian E. Lacy, chief of gastroenterology and hepatology at Dartmouth-Hitchcock Medical Center, Lebanon, N.H., said that the information about relative risk is potentially important, but he was particularly impressed by the substantial use of novel anticoagulants in non-AF patients.

“This tells me that we as gastroenterologists need to be asking more questions about exposure to anticoagulants,” Dr. Lacy said in an interview. “These data suggest that these newer drugs are being used frequently outside of labeling. We need to be aware of these changing patterns of use when trying to assess the risk of our patients for GI bleeds.”

Dr. Abraham had no financial disclosures.

PHILADELPHIA – Dabigatran and rivaroxaban, which are rapidly replacing warfarin for anticoagulation in patients with atrial fibrillation, appear to be associated with a greater risk of GI bleeding than the long-time standard in patients over the age of 65 years, according to an analysis presented at the American College of Gastroenterology (ACG).

The pattern of an increased GI bleeding risk with the newer oral anticoagulants relative to warfarin was consistent in older patients whether used for AF or for out-of-labeling indications, which were assessed separately, reported Dr. Neena S. Abraham, professor of medicine at Mayo Clinic, Scottsdale, Ariz.

“In all four cases, once patients were over the age of 65, the risk of GI bleeding increased significantly on the novel agents when compared to warfarin,” Dr. Abraham reported.

The propensity matches, based on such characteristics as GI bleeding risk factors, age, race, and concomitant medications, were drawn from 92,816 patients in a large database starting a new prescription of dabigatran, rivaroxaban, or warfarin over a recent 3-year period. With this matching, 9,860 new users of dabigatran and 20,619 new users of rivaroxaban were compared with equal number of new users of warfarin.

In the full dataset, before age stratification, the risk of total GI bleeding, particularly lower GI bleeding, appeared to be nonsignificantly lower for both dabigatran and rivaroxaban, relative to warfarin in patients with AF. In patients without AF receiving these drugs, the risk remained slightly lower on rivaroxaban but appeared to be slightly increased on dabigatran.

However, the hypothesis that bleeding risk was greater for newer agents in older patients was substantiated when the data were stratified by age. In the analysis, risk of bleeding started climbing more steeply with the newer agents as patients aged than with warfarin, with differences observed at about age 65 years.

By age 75, the hazard ratio for a GI bleed in dabigatran patients relative to warfarin in AF patients was 2.4 (95% confidence interval 1.5-3.8). In the rivaroxaban group, the HR for this risk at age 75 in AF patients was 4.0 (95% CI 2.1-7.4). In non-AF patients, the rates of GI bleeding were also significantly increased at a similar magnitude.

These data were anticipated by the initial trials that found dabigatran and rivaroxaban noninferior to warfarin for the prevention of stroke and systemic embolism, according to Dr. Abraham. Although there was heterogeneity in reported risk differences, she reported that GI bleeding was as much as 25% higher on the newer anticoagulants when compared to warfarin in older patients. These new data substantiate those findings.

“Our study is the first to evaluate GI safety in novel oral anticoagulants compared to warfarin in a real-world, multiage setting,” Dr. Abraham noted. She said these data “facilitate risk-benefit considerations” of these drugs. She further noted that the data on non-AF patients may be particularly pertinent “because this is the fastest-growing emerging market” for agents in this class.

Asked for a comment, Dr. Brian E. Lacy, chief of gastroenterology and hepatology at Dartmouth-Hitchcock Medical Center, Lebanon, N.H., said that the information about relative risk is potentially important, but he was particularly impressed by the substantial use of novel anticoagulants in non-AF patients.

“This tells me that we as gastroenterologists need to be asking more questions about exposure to anticoagulants,” Dr. Lacy said in an interview. “These data suggest that these newer drugs are being used frequently outside of labeling. We need to be aware of these changing patterns of use when trying to assess the risk of our patients for GI bleeds.”

Dr. Abraham had no financial disclosures.

Individuals with inflammatory rheumatic diseases such as inflammatory arthritis, vasculitis, and connective tissue diseases, have a threefold increase in the risk of venous thromboembolism, compared with the general population, according to a meta-analysis.

The meta-analysis of 25 studies – 10 of which included patients with rheumatoid arthritis (RA) – found those with RA were more than twice as likely to develop deep vein thrombosis or a pulmonary embolism, compared with an age- and sex-matched individuals who had other comorbidities such as diabetes, peripheral vascular disease/coronary artery disease, and malignancy (OR, 2.23; 95% confidence interval, 2.02-2.47). The RA patients had a cumulative venous thromboembolism (VTE) incidence of 2.18% (Arthritis Res. Ther. 2014;16:435 [doi:10.1186/s13075-014-0435-y]).

Ten studies comprising 54,697 patients with systemic lupus erythematosus showed a cumulative thrombosis incidence of 7.29% (95% CI, 5.82%-8.75%). Other diseases for which the investigators calculated cumulative incidence rates of VTE, based on four studies apiece, were Sjögren’s syndrome (2.18%; 95% CI, 0.79%-3.57%), inflammatory myositis (4.03%; 95% CI, 2.38%-5.67%), Antineutrophil cytoplasmic antibody vasculitis (7.97%; 95% CI, 5.67%-10.28%), and systemic sclerosis (3.13%; 95% CI, 1.73%-4.52%).

“We believe that the increased VTE risk is associated with the activity of the inflammatory diseases, rather than with the treatments used for controlling the disease,” wrote Dr. Jason Lee of the University of Western Ontario, London, and Dr. Janet Pope, of the division of rheumatology at St. Joseph’s Health Care, London, Ont.

The authors said that they had no conflicts of interest.

Individuals with inflammatory rheumatic diseases such as inflammatory arthritis, vasculitis, and connective tissue diseases, have a threefold increase in the risk of venous thromboembolism, compared with the general population, according to a meta-analysis.

The meta-analysis of 25 studies – 10 of which included patients with rheumatoid arthritis (RA) – found those with RA were more than twice as likely to develop deep vein thrombosis or a pulmonary embolism, compared with an age- and sex-matched individuals who had other comorbidities such as diabetes, peripheral vascular disease/coronary artery disease, and malignancy (OR, 2.23; 95% confidence interval, 2.02-2.47). The RA patients had a cumulative venous thromboembolism (VTE) incidence of 2.18% (Arthritis Res. Ther. 2014;16:435 [doi:10.1186/s13075-014-0435-y]).

Ten studies comprising 54,697 patients with systemic lupus erythematosus showed a cumulative thrombosis incidence of 7.29% (95% CI, 5.82%-8.75%). Other diseases for which the investigators calculated cumulative incidence rates of VTE, based on four studies apiece, were Sjögren’s syndrome (2.18%; 95% CI, 0.79%-3.57%), inflammatory myositis (4.03%; 95% CI, 2.38%-5.67%), Antineutrophil cytoplasmic antibody vasculitis (7.97%; 95% CI, 5.67%-10.28%), and systemic sclerosis (3.13%; 95% CI, 1.73%-4.52%).

“We believe that the increased VTE risk is associated with the activity of the inflammatory diseases, rather than with the treatments used for controlling the disease,” wrote Dr. Jason Lee of the University of Western Ontario, London, and Dr. Janet Pope, of the division of rheumatology at St. Joseph’s Health Care, London, Ont.

The authors said that they had no conflicts of interest.

Individuals with inflammatory rheumatic diseases such as inflammatory arthritis, vasculitis, and connective tissue diseases, have a threefold increase in the risk of venous thromboembolism, compared with the general population, according to a meta-analysis.

The meta-analysis of 25 studies – 10 of which included patients with rheumatoid arthritis (RA) – found those with RA were more than twice as likely to develop deep vein thrombosis or a pulmonary embolism, compared with an age- and sex-matched individuals who had other comorbidities such as diabetes, peripheral vascular disease/coronary artery disease, and malignancy (OR, 2.23; 95% confidence interval, 2.02-2.47). The RA patients had a cumulative venous thromboembolism (VTE) incidence of 2.18% (Arthritis Res. Ther. 2014;16:435 [doi:10.1186/s13075-014-0435-y]).

Ten studies comprising 54,697 patients with systemic lupus erythematosus showed a cumulative thrombosis incidence of 7.29% (95% CI, 5.82%-8.75%). Other diseases for which the investigators calculated cumulative incidence rates of VTE, based on four studies apiece, were Sjögren’s syndrome (2.18%; 95% CI, 0.79%-3.57%), inflammatory myositis (4.03%; 95% CI, 2.38%-5.67%), Antineutrophil cytoplasmic antibody vasculitis (7.97%; 95% CI, 5.67%-10.28%), and systemic sclerosis (3.13%; 95% CI, 1.73%-4.52%).

“We believe that the increased VTE risk is associated with the activity of the inflammatory diseases, rather than with the treatments used for controlling the disease,” wrote Dr. Jason Lee of the University of Western Ontario, London, and Dr. Janet Pope, of the division of rheumatology at St. Joseph’s Health Care, London, Ont.

The authors said that they had no conflicts of interest.

SANTA CLARA, CALIF. – When Dr. Omar Dawood demonstrated the AliveCor Heart Monitor with a new app and algorithm for detecting atrial fibrillation on stage at the Health 2.0 fall conference 2014, it showed that his heart was in normal sinus rhythm – but he had a heart rate of 135 beats per minute.

Chalk it up to the excitement of speaking before an audience of physicians and technologists about this new mobile ECG tool, Dr. Dawood said. “I’m not always that anxious.”

The AliveCor device attaches to the back of iPhones or Android-based smartphones and sells for $60-$199, depending on the model of smartphone. The Food and Drug Administration approved it in 2013, and patients have used it since March 2014. The device sends an ECG reading to a cardiologist or cardiac technician, who sends a reply within 24 hours.

With the new, free app, however, patients get an immediate result from the device showing whether or not they are likely to have atrial fibrillation. The FDA cleared the algorithm for the app in August 2014, and the company launched it on the marketplace at the Health 2.0 conference.

Validation studies have shown that the AliveCor system performs comparably to a traditional 12-lead ECG, Dr. Dawood said in a video interview.

For other recent news on studies of AliveCor in clinical settings, see our Evidence-Based Apps column.

Dr. Dawood, a surgeon by training, is a clinical adviser at AliveCor and also works for a separate technology company.

[email protected]


On Twitter @sherryboschert

SANTA CLARA, CALIF. – When Dr. Omar Dawood demonstrated the AliveCor Heart Monitor with a new app and algorithm for detecting atrial fibrillation on stage at the Health 2.0 fall conference 2014, it showed that his heart was in normal sinus rhythm – but he had a heart rate of 135 beats per minute.

Chalk it up to the excitement of speaking before an audience of physicians and technologists about this new mobile ECG tool, Dr. Dawood said. “I’m not always that anxious.”

The AliveCor device attaches to the back of iPhones or Android-based smartphones and sells for $60-$199, depending on the model of smartphone. The Food and Drug Administration approved it in 2013, and patients have used it since March 2014. The device sends an ECG reading to a cardiologist or cardiac technician, who sends a reply within 24 hours.

With the new, free app, however, patients get an immediate result from the device showing whether or not they are likely to have atrial fibrillation. The FDA cleared the algorithm for the app in August 2014, and the company launched it on the marketplace at the Health 2.0 conference.

Validation studies have shown that the AliveCor system performs comparably to a traditional 12-lead ECG, Dr. Dawood said in a video interview.

For other recent news on studies of AliveCor in clinical settings, see our Evidence-Based Apps column.

Dr. Dawood, a surgeon by training, is a clinical adviser at AliveCor and also works for a separate technology company.

[email protected]


On Twitter @sherryboschert

SANTA CLARA, CALIF. – When Dr. Omar Dawood demonstrated the AliveCor Heart Monitor with a new app and algorithm for detecting atrial fibrillation on stage at the Health 2.0 fall conference 2014, it showed that his heart was in normal sinus rhythm – but he had a heart rate of 135 beats per minute.

Chalk it up to the excitement of speaking before an audience of physicians and technologists about this new mobile ECG tool, Dr. Dawood said. “I’m not always that anxious.”

The AliveCor device attaches to the back of iPhones or Android-based smartphones and sells for $60-$199, depending on the model of smartphone. The Food and Drug Administration approved it in 2013, and patients have used it since March 2014. The device sends an ECG reading to a cardiologist or cardiac technician, who sends a reply within 24 hours.

With the new, free app, however, patients get an immediate result from the device showing whether or not they are likely to have atrial fibrillation. The FDA cleared the algorithm for the app in August 2014, and the company launched it on the marketplace at the Health 2.0 conference.

Validation studies have shown that the AliveCor system performs comparably to a traditional 12-lead ECG, Dr. Dawood said in a video interview.

For other recent news on studies of AliveCor in clinical settings, see our Evidence-Based Apps column.

Dr. Dawood, a surgeon by training, is a clinical adviser at AliveCor and also works for a separate technology company.

[email protected]


On Twitter @sherryboschert

For patients with acute venous thromboembolism, both clinical and safety outcomes were similar among seven of eight possible treatment strategies assessed in a network meta-analysis published online Sept. 16 in JAMA.

Clinicians have several treatment options but little guidance for choosing among them when managing acute VTE. Many strategies have shown promising results when assessed in single studies, but there have been few direct comparison studies. So investigators performed a network meta-analysis of 45 articles involving 44,989 patients, which enabled them to compare the safety and efficacy of eight possible approaches. The sample sizes of these studies ranged from 60 to 8,240 participants, with a median of 298. The median follow-up period was 3 months, with a range of 3-8 months.

The currently accepted standard treatment for acute VTE is the use of parenteral low-molecular-weight heparin (LMWH) for a minimum of 5 days, followed by transition to a vitamin K antagonist. This approach was compared against parenteral unfractionated heparin followed by a vitamin K antagonist; parenteral fondaparinux followed by a vitamin K antagonist; parenteral LMWH combined with dabigatran; parenteral LMWH combined with edoxaban; oral rivaroxaban; oral apixaban; and parenteral LMWH alone, said Dr. Lana A. Castellucci of the Ottawa Hospital Research Institute, University of Ottawa, and her associates.

Compared with standard parenteral LMWH plus a vitamin K antagonist, six of these approaches yielded comparable reductions in recurrent VTE and induced comparable rates of major bleeding, the investigators said (JAMA 2014 September 16 [doi:10.1001/jama.2014.10538]).

The only strategy that was less effective at reducing the rate of recurrent VTE was parenteral unfractionated heparin plus a vitamin K antagonist. However, “there are clinical circumstances that necessitate the use of unfractionated heparin, including for patients with severe renal insufficiency and those with massive or submassive pulmonary embolism who are potential candidates for thrombolysis or thrombectomy,” Dr. Castellucci and her associates noted.

Oral rivaroxaban and oral apixaban appeared to be associated with the lowest risk of major bleeding. “Future direct comparison trials, patient-level network meta-analyses, or high-quality nonrandomized studies are required to confirm our findings,” they added.

This study was supported by the Heart and Stroke Foundation of Canada, the University of Ottawa, the Canadian Institutes of Health Research, the Canadian Network and Centre for Trials Internationally, and the Heart and Stroke Foundation of Ontario. Dr. Castellucci reported no financial conflicts of interest; some of her associates reported ties to Bayer, Biomerieux, Boehringer Ingelheim, Bristol-Myers Squibb, Leo Pharma, Pfizer, and Sanofi.

*Correction, 9/17/2014: An earlier version of this article misstated the Key Clinical Point in the Vitals section. 

For patients with acute venous thromboembolism, both clinical and safety outcomes were similar among seven of eight possible treatment strategies assessed in a network meta-analysis published online Sept. 16 in JAMA.

Clinicians have several treatment options but little guidance for choosing among them when managing acute VTE. Many strategies have shown promising results when assessed in single studies, but there have been few direct comparison studies. So investigators performed a network meta-analysis of 45 articles involving 44,989 patients, which enabled them to compare the safety and efficacy of eight possible approaches. The sample sizes of these studies ranged from 60 to 8,240 participants, with a median of 298. The median follow-up period was 3 months, with a range of 3-8 months.

The currently accepted standard treatment for acute VTE is the use of parenteral low-molecular-weight heparin (LMWH) for a minimum of 5 days, followed by transition to a vitamin K antagonist. This approach was compared against parenteral unfractionated heparin followed by a vitamin K antagonist; parenteral fondaparinux followed by a vitamin K antagonist; parenteral LMWH combined with dabigatran; parenteral LMWH combined with edoxaban; oral rivaroxaban; oral apixaban; and parenteral LMWH alone, said Dr. Lana A. Castellucci of the Ottawa Hospital Research Institute, University of Ottawa, and her associates.

Compared with standard parenteral LMWH plus a vitamin K antagonist, six of these approaches yielded comparable reductions in recurrent VTE and induced comparable rates of major bleeding, the investigators said (JAMA 2014 September 16 [doi:10.1001/jama.2014.10538]).

The only strategy that was less effective at reducing the rate of recurrent VTE was parenteral unfractionated heparin plus a vitamin K antagonist. However, “there are clinical circumstances that necessitate the use of unfractionated heparin, including for patients with severe renal insufficiency and those with massive or submassive pulmonary embolism who are potential candidates for thrombolysis or thrombectomy,” Dr. Castellucci and her associates noted.

Oral rivaroxaban and oral apixaban appeared to be associated with the lowest risk of major bleeding. “Future direct comparison trials, patient-level network meta-analyses, or high-quality nonrandomized studies are required to confirm our findings,” they added.

This study was supported by the Heart and Stroke Foundation of Canada, the University of Ottawa, the Canadian Institutes of Health Research, the Canadian Network and Centre for Trials Internationally, and the Heart and Stroke Foundation of Ontario. Dr. Castellucci reported no financial conflicts of interest; some of her associates reported ties to Bayer, Biomerieux, Boehringer Ingelheim, Bristol-Myers Squibb, Leo Pharma, Pfizer, and Sanofi.

*Correction, 9/17/2014: An earlier version of this article misstated the Key Clinical Point in the Vitals section. 

For patients with acute venous thromboembolism, both clinical and safety outcomes were similar among seven of eight possible treatment strategies assessed in a network meta-analysis published online Sept. 16 in JAMA.

Clinicians have several treatment options but little guidance for choosing among them when managing acute VTE. Many strategies have shown promising results when assessed in single studies, but there have been few direct comparison studies. So investigators performed a network meta-analysis of 45 articles involving 44,989 patients, which enabled them to compare the safety and efficacy of eight possible approaches. The sample sizes of these studies ranged from 60 to 8,240 participants, with a median of 298. The median follow-up period was 3 months, with a range of 3-8 months.

The currently accepted standard treatment for acute VTE is the use of parenteral low-molecular-weight heparin (LMWH) for a minimum of 5 days, followed by transition to a vitamin K antagonist. This approach was compared against parenteral unfractionated heparin followed by a vitamin K antagonist; parenteral fondaparinux followed by a vitamin K antagonist; parenteral LMWH combined with dabigatran; parenteral LMWH combined with edoxaban; oral rivaroxaban; oral apixaban; and parenteral LMWH alone, said Dr. Lana A. Castellucci of the Ottawa Hospital Research Institute, University of Ottawa, and her associates.

Compared with standard parenteral LMWH plus a vitamin K antagonist, six of these approaches yielded comparable reductions in recurrent VTE and induced comparable rates of major bleeding, the investigators said (JAMA 2014 September 16 [doi:10.1001/jama.2014.10538]).

The only strategy that was less effective at reducing the rate of recurrent VTE was parenteral unfractionated heparin plus a vitamin K antagonist. However, “there are clinical circumstances that necessitate the use of unfractionated heparin, including for patients with severe renal insufficiency and those with massive or submassive pulmonary embolism who are potential candidates for thrombolysis or thrombectomy,” Dr. Castellucci and her associates noted.

Oral rivaroxaban and oral apixaban appeared to be associated with the lowest risk of major bleeding. “Future direct comparison trials, patient-level network meta-analyses, or high-quality nonrandomized studies are required to confirm our findings,” they added.

This study was supported by the Heart and Stroke Foundation of Canada, the University of Ottawa, the Canadian Institutes of Health Research, the Canadian Network and Centre for Trials Internationally, and the Heart and Stroke Foundation of Ontario. Dr. Castellucci reported no financial conflicts of interest; some of her associates reported ties to Bayer, Biomerieux, Boehringer Ingelheim, Bristol-Myers Squibb, Leo Pharma, Pfizer, and Sanofi.

*Correction, 9/17/2014: An earlier version of this article misstated the Key Clinical Point in the Vitals section.