Treating patients with triple therapy – warfarin, aspirin and clopidogrel – has the same rates of adverse cardiac events but a higher incidence of bleeding requiring hospitalization in the two years following discharge, as compared to dual antiplatelet treatment, in patients who have a history of atrial fibrillation (AFib) and had a myocardial infarction treated with percutaneous coronary intervention (PCI), according to a study published Aug. 3 in the Journal of the American College of Cardiology.

Using data from the ACC’s ACTION Registry-GWTG linked with Centers for Medicare and Medicaid Services data, researchers examined records between January 2007 and December 2010 from nearly 5,000 patients 65 years or older with a history of AFib presenting with a myocardial infarction and being treated with PCI.

Researchers found that almost 28 percent of patients were discharged on triple therapy compared to 72 percent discharged on dual antiplatelet therapy. Those receiving triple therapy were more likely to be male, have a history of either PCI or coronary artery bypass surgery, and have a history of stroke. These patients also were frequently already on warfarin before admission to the hospital. In contrast, patients released on a dual antiplatelet therapy were more likely to have had an in-hospital major bleeding event. 

Results showed that after adjusting for patient, treatment, and hospital characteristics, triple therapy was not associated with a lower two-year risk of major adverse cardiac events compared to dual antiplatelet therapy. The risk of bleeding, including intracranial bleeding, requiring hospitalization within two years after discharge was more than 6 percent higher for patients on triple therapy compared with those on a dual-therapy regimen.   

To verify findings from the primary study, researchers analyzed records from 1,591 Medicare Part D patients and found that 93 percent continued to take warfarin 90 days after being discharged from the hospital. The findings from this secondary study were consistent with the results from the primary study: the risk of major adverse cardiac events had not been reduced, and the bleeding risk was higher. 

Connie N. Hess, MD, MHS, FACC, the study’s lead author and assistant professor, Department of Medicine, Division of Cardiology at Duke University School of Medicine and a member of the Duke Clinical Research Institute, notes that the increased risk of bleeding without apparent benefit of triple therapy observed in this study suggests that clinicians should carefully consider the risk-to-benefit ratio of triple therapy use in older AFib patients who have had a heart attack treated with PCI. She adds that further prospective studies of different combinations of anti-clotting agents are needed to define the optimal treatment regimen for this population.

In an accompanying editorial, Javier A. Valle, MD, and John C. Messenger, MD, FACC, from the Division of Cardiology at the University of Colorado School of Medicine, write that while the benefits of triple therapy for preventing major adverse cardiac events remain “troublingly uncertain” the data are convincing for bleeding. They add that recent investigations have focused on redefining the agents used in triple therapy. 

“When it comes to antithrombotic therapy, ‘more’ does not appear to be ‘better.’ Can we replace ‘more’ with a better alternative? Unfortunately, the answer to date is ‘not yet,’” they conclude. 

Keywords: ACTION Registry, National Cardiovascular Data Registries, Aspirin, Atrial Fibrillation, Centers for Medicare and Medicaid Services, U.S., Coronary Artery Bypass, Myocardial Infarction, Percutaneous Coronary Intervention, Warfarin

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