By Jeffrey Zimmet, MD, PhD

Associate Professor of Medicine, University of California, San Francisco; Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center

Dr. Zimmet reports no financial relationships relevant to this field of study.

SOURCE: Xian Y, et al. The association of discharge aspirin dose with outcomes after acute myocardial infarction: Insights from the TRANSLATE-ACS Study. Circulation 2015. pii: CIRCULATIONAHA.114.014992. [Epub ahead of print].

Choosing an optimal maintenance dose of aspirin has been a matter of substantial debate for years. In the post-myocardial infarction (MI) setting, high-dose aspirin (325 mg/day) has been most commonly prescribed. This is despite data from observational and randomized trials suggesting a lack of benefit, the largest of which was the CURRENT-OASIS 7 trial, published in 2010. The American College of Cardiology/American Heart Association guidelines have changed in recent years to recommend low-dose rather than high-dose aspirin for maintenance therapy.

A recent analysis examined contemporary aspirin dosing in the TRANSLATE-ACS trial, which was a prospective, multicenter observational study of more than 12,000 ST segment elevation myocardial infarction or non-ST segment elevation myocardial infarction patients enrolled between 2010 and 2012 who were treated with percutaneous coronary intervention (PCI) and adenosine diphosphate (ADP) receptor inhibitors. Data, including discharge medications and outcomes, were tracked, and follow-up was performed at 6 weeks and at 6, 12, and 15 months post MI.

Of 10,213 patients eligible for analysis, 6387 (62.6%) received high-dose aspirin (325 mg) and 3826 (37.5%) received low-dose aspirin (81 mg) at discharge. Of those discharged on high-dose aspirin, nearly 35% were switched to low-dose by 6 months. In contrast, approximately 8% of patients discharged on low-dose aspirin were changed to high-dose by 6 months.

At 6 months post-discharge, the incidence of major adverse coronary events (MACE) was 8.2% in the high-dose aspirin group, compared with 9.2% in the low-dose group, which was not significantly different, even after multivariable adjustment. However, BARC-defined bleeding events, predominantly minor BARC type 1 or 2 bleeds not requiring hospitalization, were more frequent with high-dose aspirin. Results were unchanged after inverse probability-weighted propensity adjustment. MACE events generally were not different across subgroups defined by age, sex, home aspirin use, and type of ADP receptor antagonist used (clopidogrel vs prasugrel or ticagrelor) as part of the dual antiplatelet therapy regimen. However, the risk of bleeding associated with high-dose aspirin use was slightly increased in younger patients, men, those using aspirin before admission, and those prescribed higher-potency ADP receptor antagonists (prasugrel or ticagrelor, as opposed to clopidogrel) at discharge.

The authors concluded that high-dose aspirin is prescribed at discharge in a majority (nearly two-thirds) of U.S. MI patients treated with PCI, despite no apparent benefit in terms of MACE and a measurable increase in minor bleeding events by 6 months. They argue that their data support current guideline recommendations for low-dose as opposed to high-dose aspirin for maintenance therapy following MI.

COMMENTARY

Just a few short years ago, the dosing of aspirin for maintenance therapy in general, and after PCI specifically, was relatively complex. Official recommendations called for a higher dose of aspirin in the immediate post-PCI period, with conversion to a lower dose thereafter. Initial recommendations in the era of first-generation drug-eluting stents even called for differential periods of high-dose aspirin with sirolimus- vs paclitaxel-eluting stents. I can easily recall the discussion during our department cath conference after publication of the 2011 update to the ACCF/AHA/SCAI guidelines for percutaneous coronary intervention, which contained the following language as a IIa recommendation: “After PCI, it is reasonable to use aspirin 81 mg per day in preference to higher maintenance doses.” Would we as a department choose to follow this new recommendation, or would we each make our own choices? A spirited debate ensued, with some arguing fervently for maintaining an initial period of high-dose aspirin.

What a long way we have come in only a few short years, at least on this one issue. The current study provides further evidence of a lack of benefit to high-dose maintenance aspirin, along with a suggestion of harm. The latest guidelines specifically recommend the use of low-dose aspirin for maintenance purposes, and for good reason. We should adopt low-dose aspirin for outpatient use in the United States, as much of the world has already done, and in doing so simplify treatment recommendations for ourselves and for our patients.