Ticagrelor in Patients With Acute Coronary Syndromes and Stroke

Phase 3 prospective randomized trials are designed and have statistical power for the investigation of 1 major hypothesis in a predefined population using predefined clinical end points. These large outcome trials are conducted following rules and regulations specified by Good Clinical Practice and the ethical principles of the Declaration of Helsinki to maintain the highest scientific validity and ethical standards and minimize bias. Predefined, subgroup analyses are by definition underpowered for evaluation of the primary and secondary events but often performed to generate hypotheses for further understanding of the effects and side effects in important subgroups.The Platelet Inhibition and Patient Outcome (PLATO) trial successfully tested its main hypothesis: that ticagrelor compared with clopidogrel would result in a lower risk of recurrent thrombotic events in a broad patient population with acute coronary syndromes.1 An academic executive committee was responsible for the design and the medical, scientific, and operational conduct of PLATO; expert sites and investigators conducted the trial, which was monitored closely by an independent data and safety monitoring board; and all primary and secondary efficacy and safety events were adjudicated by an independent committee of expert cardiologists and neurologists blinded to assigned treatment. Two independent academic groups have full access to the PLATO database and have performed all analyses for publication.Patients with acute coronary syndromes and with a history of stroke or transient ischemic attacks (TIA) are at particularly high risk for recurrent cardiovascular events, including death and myocardial infarction, as well as bleeding complications, including an increased risk of intracranial bleeding. In this high-risk population, the balance between safety and efficacy of antithrombotic treatment is therefore particularly important. Establishing the clinical efficacy and safety of ticagrelor versus clopidogrel in patients with previous stroke or TIA was a prespecified subgroup analysis of PLATO included in the appendix …