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Ticagrelor or clopidogrel in DAPT for acute coronary syndromes: A call for a stepwise approach?

Dual antiplatelet therapy with aspirin combined with ticagrelor or prasugrel is advocated as first-line therapy for patients with an acute coronary syndrome (ACS). Both ticagrelor and prasugrel were associated with higher rates of non-coronary artery bypass grafting-related TIMI major bleeding in PLATO and TRITON-TIMI 38, their respective large, international randomized trials versus clopidogrel. However, this risk was offset by a clear decrease in the primary endpoint, a composite of death, myocardial infarction or stroke.

Coinciding with presentation as Late Breaking Registry in Barcelona during the Congress of the European Society of Cardiology, Eurointervention publishes the results of CHANGE-DAPT from Paolo Zocca et al., a solid registry of ACS patients treated with clopidogrel or ticagrelor in two consecutive periods. Differently from PLATO, CHANGE-DAPT included only patients undergoing percutaneous coronary intervention and treated with drug-eluting stents. It therefore represent a meaningful snapshot of current practice, particularly in view of its scrupolous and systematic conduction, with 99.3% follow-up completion at 12 months.

Surprisingly, the study questions the primacy of ticagrelor as first-line therapy in ACS, due to increased rates of net adverse cerebral or cardiac events, driven by increased bleeding. An accompanying Editorial of Davide Capodanno puts these results into perspective, critically appraising the strengths of the registry but also the limitations that finally discourage the reader from confuting the conclusions of PLATO. Even so, the results of CHANGE-DAPT are thought-provoking, in that they corroborate the results of TOPIC, a recent small randomized study suggesting that tailoring antiplatelet therapy with a stepwise approach is a concept worthy of further investigation in large randomized studies.

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