Triple Therapy May Increase Major Bleeding in Older Patients with Acute MI, AF

NEW YORK - Compared with dual antiplatelet therapy (DAPT), triple therapy increases the risk of major bleeding without altering the rates of myocardial infarction (MI), stroke, or death in older patients with acute MI and atrial fibrillation (AF), according to a registry study.

"These data suggest that the risk-benefit ratio of triple therapy in older patients with myocardial infarction and atrial fibrillation should be carefully considered," Dr. Connie N. Hess, from Duke Clinical Research Institute, Duke University, Durham, North Carolina, told Reuters Health by email. "However, these results need to be confirmed with prospective studies; a number of ongoing randomized clinical trials may help to provide insight."

Therapeutic decisions for older patients with acute MI and AF are challenging, not least because they have been excluded from or underrepresented in clinical trials.

Dr. Hess's team linked data from the ACTION Registry Get With The Guidelines and Medicare administrative claims to compare outcomes with DAPT or triple therapy (DAPT plus warfarin) in 4959 patients age 65 and older with acute MI and AF who underwent coronary stenting.

More patients were discharged on DAPT (72.4%) than on triple therapy (27.6%), the researchers report in the August 11 issue of the Journal of the American College of Cardiology (JACC), available online now.

The primary effectiveness outcome, major adverse cardiac events (MACE, including death or readmission for MI or stroke) at two years, did not differ in incidence between triple therapy (32.6%) and DAPT (32.7%), and there were no significant differences in the incidences of the individual MACE components.

In contrast, the cumulative incidence of bleeding requiring hospitalization within two years of discharge was significantly higher for patients on triple therapy (17.6%) than for patients on DAPT (11.0%; p<0.0001), and this difference persisted after adjustment for case-mix, treatment, and hospital features.

Triple therapy was also associated with a 2.04-fold higher risk of intracranial hemorrhage, compared with DAPT.

The association of triple therapy with MACE and bleeding outcomes was similar for patients older and younger than 75, for men and women, for patients with low and high predicted stroke risk, for patients with shorter versus longer duration of AF, for patients treated with drug-eluting versus bare-metal stents, and for patients presenting with non-ST-segment elevation MI versus ST-segment elevation MI.

"Until we have data from prospective studies to define optimal antithrombotic use in older patients with myocardial infarction and atrial fibrillation, providers should be especially mindful of an individual's bleeding risk when deciding to prescribe triple therapy," Dr. Hess concluded.

Dr. John C. Messenger, from the University of Colorado School of Medicine, Aurora, cowrote an editorial related to this report. He told Reuters Health by email, "We should ideally look to minimize duration of triple therapy, keeping it as short as possible. We also need to enroll patients in trials designed to evaluate double therapy without the use of aspirin."

"With the change in guidelines recommending oral anticoagulation for patients with atrial fibrillation at lower risk for ischemic stroke, the negative impact of bleeding related to the use of triple therapy may far outweigh the benefit of reduction of ischemic stroke," Dr. Messenger said. "We obviously need further study on this topic."

Dr. Andrea Rubboli, from Ospedale Maggiore, Bologna, Italy, has researched how best to treat these patients. He told Reuters Health by email, "Given that I practice in Europe, where current guidelines recommend triple therapy for these patients, what I found most surprising is the relatively small proportion of AF patients treated with (percutaneous coronary intervention) PCI who were discharged on triple therapy. Conversely, it was not surprising that DAPT was comparable to triple therapy in terms of MACE and superior in terms of bleeding because this has been previously reported and the several limitations of this kind of analysis (especially the lack of information on the therapy really ongoing at the time of event) may account for that."

"Triple therapy confirmed to be the best treatment for these patients," Dr. Rubboli concluded. "While not reducing MACE versus DAPT, it is indeed significantly more effective in reducing the most feared and devastating complication of AF, that is, stroke. Given the increased risk of bleeding, however, great care should be put in monitoring such therapy."

Dr. Nikolaus Sarafoff, from Ludwig-Maximilians University, Munich, Germany, told Reuters Health by email, "In my opinion, one major limitation of the study is that only 7.7% of patients in the DAPT group were on oral anticoagulation (OAC) at randomization as compared to 62.1% in the triple arm. This shows clearly that physicians felt that patients in the DAPT arm had no real indication for OAC (even before the myocardial infarction with PCI occurred) and this makes the comparison of the two groups very difficult."

"The indication for triple therapy and the optimal antithrombotic treatment should be taken carefully, weighing the bleeding and the ischemic risk of the patient," Dr. Sarafoff concluded. "Several options to reduce bleeding complications in this high-risk population exist, such as omitting aspirin, shortening the duration of therapy. The results of the present study cannot supplant current guidelines that state clearly that patients with atrial fibrillation and a CHA2DS2-VASc Score 2 are in need of OAC no matter whether concomitant antiplatelet therapy is needed."

The American College of Cardiology Foundation's National Cardiovascular Data Registry supported this study. Three coauthors reported relevant relationships.

NEW YORK - Compared with dual antiplatelet therapy (DAPT), triple therapy increases the risk of major bleeding without altering the rates of myocardial infarction (MI), stroke, or death in older patients with acute MI and atrial fibrillation (AF), according to a registry study.

"These data suggest that the risk-benefit ratio of triple therapy in older patients with myocardial infarction and atrial fibrillation should be carefully considered," Dr. Connie N. Hess, from Duke Clinical Research Institute, Duke University, Durham, North Carolina, told Reuters Health by email. "However, these results need to be confirmed with prospective studies; a number of ongoing randomized clinical trials may help to provide insight."

Therapeutic decisions for older patients with acute MI and AF are challenging, not least because they have been excluded from or underrepresented in clinical trials.

Dr. Hess's team linked data from the ACTION Registry Get With The Guidelines and Medicare administrative claims to compare outcomes with DAPT or triple therapy (DAPT plus warfarin) in 4959 patients age 65 and older with acute MI and AF who underwent coronary stenting.

More patients were discharged on DAPT (72.4%) than on triple therapy (27.6%), the researchers report in the August 11 issue of the Journal of the American College of Cardiology (JACC), available online now.

The primary effectiveness outcome, major adverse cardiac events (MACE, including death or readmission for MI or stroke) at two years, did not differ in incidence between triple therapy (32.6%) and DAPT (32.7%), and there were no significant differences in the incidences of the individual MACE components.

In contrast, the cumulative incidence of bleeding requiring hospitalization within two years of discharge was significantly higher for patients on triple therapy (17.6%) than for patients on DAPT (11.0%; p<0.0001), and this difference persisted after adjustment for case-mix, treatment, and hospital features.

Triple therapy was also associated with a 2.04-fold higher risk of intracranial hemorrhage, compared with DAPT.

The association of triple therapy with MACE and bleeding outcomes was similar for patients older and younger than 75, for men and women, for patients with low and high predicted stroke risk, for patients with shorter versus longer duration of AF, for patients treated with drug-eluting versus bare-metal stents, and for patients presenting with non-ST-segment elevation MI versus ST-segment elevation MI.

"Until we have data from prospective studies to define optimal antithrombotic use in older patients with myocardial infarction and atrial fibrillation, providers should be especially mindful of an individual's bleeding risk when deciding to prescribe triple therapy," Dr. Hess concluded.

Dr. John C. Messenger, from the University of Colorado School of Medicine, Aurora, cowrote an editorial related to this report. He told Reuters Health by email, "We should ideally look to minimize duration of triple therapy, keeping it as short as possible. We also need to enroll patients in trials designed to evaluate double therapy without the use of aspirin."

"With the change in guidelines recommending oral anticoagulation for patients with atrial fibrillation at lower risk for ischemic stroke, the negative impact of bleeding related to the use of triple therapy may far outweigh the benefit of reduction of ischemic stroke," Dr. Messenger said. "We obviously need further study on this topic."

Dr. Andrea Rubboli, from Ospedale Maggiore, Bologna, Italy, has researched how best to treat these patients. He told Reuters Health by email, "Given that I practice in Europe, where current guidelines recommend triple therapy for these patients, what I found most surprising is the relatively small proportion of AF patients treated with (percutaneous coronary intervention) PCI who were discharged on triple therapy. Conversely, it was not surprising that DAPT was comparable to triple therapy in terms of MACE and superior in terms of bleeding because this has been previously reported and the several limitations of this kind of analysis (especially the lack of information on the therapy really ongoing at the time of event) may account for that."

"Triple therapy confirmed to be the best treatment for these patients," Dr. Rubboli concluded. "While not reducing MACE versus DAPT, it is indeed significantly more effective in reducing the most feared and devastating complication of AF, that is, stroke. Given the increased risk of bleeding, however, great care should be put in monitoring such therapy."

Dr. Nikolaus Sarafoff, from Ludwig-Maximilians University, Munich, Germany, told Reuters Health by email, "In my opinion, one major limitation of the study is that only 7.7% of patients in the DAPT group were on oral anticoagulation (OAC) at randomization as compared to 62.1% in the triple arm. This shows clearly that physicians felt that patients in the DAPT arm had no real indication for OAC (even before the myocardial infarction with PCI occurred) and this makes the comparison of the two groups very difficult."

"The indication for triple therapy and the optimal antithrombotic treatment should be taken carefully, weighing the bleeding and the ischemic risk of the patient," Dr. Sarafoff concluded. "Several options to reduce bleeding complications in this high-risk population exist, such as omitting aspirin, shortening the duration of therapy. The results of the present study cannot supplant current guidelines that state clearly that patients with atrial fibrillation and a CHA2DS2-VASc Score 2 are in need of OAC no matter whether concomitant antiplatelet therapy is needed."

The American College of Cardiology Foundation's National Cardiovascular Data Registry supported this study. Three coauthors reported relevant relationships.

NEW YORK - Compared with dual antiplatelet therapy (DAPT), triple therapy increases the risk of major bleeding without altering the rates of myocardial infarction (MI), stroke, or death in older patients with acute MI and atrial fibrillation (AF), according to a registry study.

"These data suggest that the risk-benefit ratio of triple therapy in older patients with myocardial infarction and atrial fibrillation should be carefully considered," Dr. Connie N. Hess, from Duke Clinical Research Institute, Duke University, Durham, North Carolina, told Reuters Health by email. "However, these results need to be confirmed with prospective studies; a number of ongoing randomized clinical trials may help to provide insight."

Therapeutic decisions for older patients with acute MI and AF are challenging, not least because they have been excluded from or underrepresented in clinical trials.

Dr. Hess's team linked data from the ACTION Registry Get With The Guidelines and Medicare administrative claims to compare outcomes with DAPT or triple therapy (DAPT plus warfarin) in 4959 patients age 65 and older with acute MI and AF who underwent coronary stenting.

More patients were discharged on DAPT (72.4%) than on triple therapy (27.6%), the researchers report in the August 11 issue of the Journal of the American College of Cardiology (JACC), available online now.

The primary effectiveness outcome, major adverse cardiac events (MACE, including death or readmission for MI or stroke) at two years, did not differ in incidence between triple therapy (32.6%) and DAPT (32.7%), and there were no significant differences in the incidences of the individual MACE components.

In contrast, the cumulative incidence of bleeding requiring hospitalization within two years of discharge was significantly higher for patients on triple therapy (17.6%) than for patients on DAPT (11.0%; p<0.0001), and this difference persisted after adjustment for case-mix, treatment, and hospital features.

Triple therapy was also associated with a 2.04-fold higher risk of intracranial hemorrhage, compared with DAPT.

The association of triple therapy with MACE and bleeding outcomes was similar for patients older and younger than 75, for men and women, for patients with low and high predicted stroke risk, for patients with shorter versus longer duration of AF, for patients treated with drug-eluting versus bare-metal stents, and for patients presenting with non-ST-segment elevation MI versus ST-segment elevation MI.

"Until we have data from prospective studies to define optimal antithrombotic use in older patients with myocardial infarction and atrial fibrillation, providers should be especially mindful of an individual's bleeding risk when deciding to prescribe triple therapy," Dr. Hess concluded.

Dr. John C. Messenger, from the University of Colorado School of Medicine, Aurora, cowrote an editorial related to this report. He told Reuters Health by email, "We should ideally look to minimize duration of triple therapy, keeping it as short as possible. We also need to enroll patients in trials designed to evaluate double therapy without the use of aspirin."

"With the change in guidelines recommending oral anticoagulation for patients with atrial fibrillation at lower risk for ischemic stroke, the negative impact of bleeding related to the use of triple therapy may far outweigh the benefit of reduction of ischemic stroke," Dr. Messenger said. "We obviously need further study on this topic."

Dr. Andrea Rubboli, from Ospedale Maggiore, Bologna, Italy, has researched how best to treat these patients. He told Reuters Health by email, "Given that I practice in Europe, where current guidelines recommend triple therapy for these patients, what I found most surprising is the relatively small proportion of AF patients treated with (percutaneous coronary intervention) PCI who were discharged on triple therapy. Conversely, it was not surprising that DAPT was comparable to triple therapy in terms of MACE and superior in terms of bleeding because this has been previously reported and the several limitations of this kind of analysis (especially the lack of information on the therapy really ongoing at the time of event) may account for that."

"Triple therapy confirmed to be the best treatment for these patients," Dr. Rubboli concluded. "While not reducing MACE versus DAPT, it is indeed significantly more effective in reducing the most feared and devastating complication of AF, that is, stroke. Given the increased risk of bleeding, however, great care should be put in monitoring such therapy."

Dr. Nikolaus Sarafoff, from Ludwig-Maximilians University, Munich, Germany, told Reuters Health by email, "In my opinion, one major limitation of the study is that only 7.7% of patients in the DAPT group were on oral anticoagulation (OAC) at randomization as compared to 62.1% in the triple arm. This shows clearly that physicians felt that patients in the DAPT arm had no real indication for OAC (even before the myocardial infarction with PCI occurred) and this makes the comparison of the two groups very difficult."

"The indication for triple therapy and the optimal antithrombotic treatment should be taken carefully, weighing the bleeding and the ischemic risk of the patient," Dr. Sarafoff concluded. "Several options to reduce bleeding complications in this high-risk population exist, such as omitting aspirin, shortening the duration of therapy. The results of the present study cannot supplant current guidelines that state clearly that patients with atrial fibrillation and a CHA2DS2-VASc Score 2 are in need of OAC no matter whether concomitant antiplatelet therapy is needed."

The American College of Cardiology Foundation's National Cardiovascular Data Registry supported this study. Three coauthors reported relevant relationships.