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Journal of the American College of Cardiology

Clinical Articles, Lead Article

No benefit in adding third antithrombotic

Triple therapy is no better than dual antiplatelet therapy in preventing major adverse cardiac events in older patients with atrial fibrillation who had a myocardial infarction (MI) treated with angioplasty, and triple therapy resulted in more complications, according to a study published recently in the Journal of the American College of Cardiology.1

When compared with patients receiving only dual antiplatelet treatment, patients on a triple therapy regimen – treated with warfarin, as well as two antiplatelet medications – had the same rates of adverse cardiac events but had a higher incidence of bleeding requiring hospitalisation in the two years following discharge.

Using data from the  National Cardiovascular Data Registry ACTION–Get With the Guidelines (AR-G), 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 atrial fibrillation presenting with an MI and being treated with angioplasty and placement of a stent.

During the study period, researchers examined major adverse cardiac events, including death and readmission due to an MI or stroke, as well as readmission due to bleeding.

Dr Connie N Hess (Duke University School of Medicine)

Dr Connie N Hess (Duke University School of Medicine)

Researchers found that almost 28% of patients were discharged on triple therapy compared to 72% discharged on dual antiplatelet therapy. Those receiving triple therapy were more likely to be male, have a history of either angioplasty 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 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 requiring hospitalisation within two years after discharge was more than 6% higher for patients on triple therapy compared with those on a dual-therapy regimen.

To verify findings from the primary study, researchers analysed records from 1,591 Medicare Part D patients and found 93% 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.

Dr Connie N Hess, the study’s lead author (Duke University School of Medicine), said: “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 atrial fibrillation patients who have had a heart attack treated with angioplasty. 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, Drs Javier A Valle and John C Messenger, both from the University of Colorado School of Medicine, USA, wrote 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.

Dr Valentin Fuster, editor-in-chief of the Journal of the American College of Cardiology, acknowledged that the critical question to be answered at present is whether oral anticoagulants plus a single platelet inhibitor – such as clopidogrel – is of a higher benefit-to-risk than triple therapy or dual antiplatelet therapy.

At this point, however, Valle and Messenger note that “more” does not appear to be “better.” They conclude by asking, “Can we replace ‘more’ with a better alternative?” The answer to date, they say, is “not yet.”


1. Hess CN, Peterson ED, Peng A, et al. Use and outcomes of triple therapy among older patients with acute myocardial infarction and atrial fibrillation.  J Am Coll Cardiol 2015;66:616–27.

Published on: September 30, 2015

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  • ArrhythmiaAlliance
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