Study Summary

The POPular AGE trial was a prospective, randomized, open-label study with a blinded clinical event committee, designed to address optimal dual antiplatelet therapy (DAPT) in elderly individuals, who have an inherent increased risk of bleeding. Patients aged ≥70 years admitted for NSTE-ACS were randomly assigned to aspirin and either clopidogrel (n = 501) or ticagrelor or prasugrel (n = 502) for 12 months. The primary safety endpoint of bleeding (as defined in the PLATO trial) was found in 17.6% of the clopidogrel group compared with 23.1% of the prasugrel/ticagrelor arm (P = 0.03). The primary efficacy endpoint — a composite of death, MI, stroke, and bleeding — occurred in 27.3% of the clopidogrel group compared with 30.7% of the ticagrelor/prasugrel group (P for noninferiority = 0.06).

Commentary

Study Strengths: This study addressed an important clinical question, which will become ever more relevant as life expectancy increases and treatment populations age. The committee responsible for determining clinical events was blinded to the treatment arm.

Study Limitations: This study was not double-blinded. As the population of this study was of Dutch origin, the generalizability of the results to other populations is unclear, and this study should be repeated with a more diverse patient population. Adherence to the study drug was only 51% in the ticagrelor/prasugrel group, but 76% in the clopidogrel group, which might have affected the primary efficacy outcome. Many of the patients received DAPT prior to randomization, which may further cloud the results.

Next Steps/Clinical Perspectives: In patients aged ≥70 years with NSTE-ACS, clopidogrel was associated with less bleeding without a significant increase in major adverse cardiac events when compared with more-potent P2Y12 inhibitors. As elderly patients are underrepresented in many clinical trials, this study provides guidance for the use of antiplatelet agents in this population.

Trial Reference

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Presented by Marieke E. Gimbel at the European Society of Cardiology Congress, Paris, France, August 31 2019.