This post was authored by Payal Kohli, MD, fellow-in-training at the University of California San Francisco.

Although the treatment of acute coronary syndromes (ACS) has been standardized with an extensive evidence base for most therapeutic interventions, the evidence base for optimal aspirin dosing following ACS remains uncertain. Early ACS trials of secondary prevention have used a variety of doses, ranging from 75 mg to 325 mg. The efficacy and safety profiles within the spectrum of aspirin dosing depends on multiple factors, including the concomitant administration of other medications.

Recent subgroup analyses of the PLATO study, in which patients with ACS were randomized to receive either the potent P2Y12 receptor antagonist ticagrelor or the first-generation thienopyridine clopidogrel, in addition to aspirin (dose of aspirin left to discretion of local investigator), raised questions about the safety of aspirin dosing in combination with a potent thienopyridine. This trial demonstrated a benefit of ticagrelor compared with clopidogrel in the reduction of recurrent cardiovascular events. Within the trial, however, an apparent decreased efficacy of ticagrelor was noted in North American subjects. Subsequent analysis of this finding suggested that it might have been related to the reduced efficacy of ticagrelor in combination with the higher doses of aspirin more commonly prescribed in North America. For this reason, the U.S. Food and Drug Administration issued a black box warning advising against the use of high-dose aspirin with ticagrelor.

Recently my colleagues and I sought to investigate whether there is a relationship between aspirin dose and the potent antiplatelet agent prasugrel in the TRITON-TIMI 38 study. In TRITON-TIMI 38, we classified 12,860 patients into low-dose (<150 mg) or high-dose (≥150 mg) aspirin groups based on discharge dose. We identified independent correlates of dose selection and studied the impact of aspirin dose on clinical effects of prasugrel.

As expected, and probably a result of historical prescribing practices, there was significant geographical variation in aspirin dosing, with North American patients receiving high-dose aspirin more frequently than other countries (66 percent vs. 28 percent).  Also not surprising were the clinical factors correlating with low-dose or high-dose aspirin. These included prior percutaneous coronary intervention, prior myocardial infarction (MI), and use of aspirin prior to randomization. Independent characteristics associated with use of low-dose aspirin included age ≥75 years, white race, and use of bivalirudin or a glycoprotein IIb/IIIa inhibitor during coronary intervention, probably due to higher comorbidities in this population.

We found that unlike ticagrelor, prasugrel had lower rates of the primary efficacy endpoint and higher rates of the primary safety endpoint compared with clopidogrel, regardless of low-dose or high-dose aspirin.  Because there was no clinically meaningful interaction of aspirin with prasugrel, this suggests that previous observations with potent antiplatelet agents indicating differential results are not universal to this class of medications.

Physicians treating patients after ACS, especially those in North America, ought to be cognizant of what dose of aspirin is prescribed and its risks and benefits. Based on our observational study of a larger randomized trial, there does not appear to be an interaction (either for efficacy or safety) between prasugrel and high dose aspirin. Additional prospective randomized controlled trials may definitively resolve the question of optimal aspirin dosing and its role within the current medical armamentarium of medical options to manage ACS.

< Back to Listings