Lessons from platelet inhibition and patient outcomes

Ticagrelor is a new, direct acting, reversibly binding P2Y12 receptor antagonist with more potent inhibition of platelets than clopidogrel and which does not require metabolic activation. It was compared with clopidogrel, on a background of the standard of care in a randomized trial in the Platelet Inhibition and Patient Outcomes (PLATO) study, on patients with acute coronary syndrome (ACS). The purpose was to evaluate the efficacy and safety results from the global, prospective trial in a broad population [ST-elevation myocardial infarction (STEMI) and non-ST elevation myocardial infarction (NSTEMI) patients] with ACS.

The main findings were a significant reduction of the primary outcome (death from vascular causes/myocardial infarction/stroke) with ticagrelor versus clopidogrel [9.8 versus 11.7% (hazard ratio 0.84; 95% confidence interval: 0.77-0.92); P < 0.001] without a significant increase in PLATO-defined major bleeding (11.6 versus 11.2%, respectively; P = 0.43), but a higher occurrence of noncoronary artery bypass grafting (CABG) related major bleeding (4.5 versus 3.8%; P = 0.026). In addition, there was a significant reduction in vascular mortality (4.0 versus 5.1%; P = 0.001). The findings were consistent in all subgroups, such as for STEMI, NSTEMI, planned invasive or noninvasive strategy, diabetes, renal function, and CABG.

Among patients with an ACS with or without ST-segment elevation, treatment with ticagrelor, as compared with clopidogrel, significantly reduced the rate of death from vascular causes, myocardial infarction, or stroke without an increase in the rate of overall major bleeding but with an increase in the rate of nonprocedure-related bleeding.