Ticagrelor in Patients With Acute Coronary Syndromes and Stroke

Abstract

P hase 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 of the primary trial publication.2 Among the 18 624 patients randomized in PLATO, 1152 (6.2%) were reported as having a history of stroke or TIA by the investigators. These patients presented higher rates of the primary composite end point, myocardial infarction, death, stroke, major bleeding and intracranial bleeding as compared with those patients without previous stroke or TIA. 3 The reductions of the primary and secondary end points of ticagrelor versus clopidogrel were consistent with the overall PLATO trial results. Thus, the relative reduction of the primary end point with ticagrelor compared with clopidogrel was 13% in patients with and 16% in patients without a history of previous stroke or TIA, with no significant treatment-by-stroke history interaction test (P=0.39) after multivariable adjustment. The relative reduction of all-cause death, with ticagrelor versus clopidogrel, was 38% and 19% in patients with or without a prev...

Antithrombotic Therapy in Patients with Coronary Artery Disease and Prior Stroke

“…In this subgroup, ticagrelor consistently reduced the primary composite outcome (HR 0.87, 95% CI 0.66–1.13; interaction p = 0.84) and total mortality (HR 0.62; 95% CI 0.42–0.91) at 1 year. The rate of bleedings was similar in both arms, and intracranial hemorrhage (ICH) was rare [ 16 ]. Therefore, ticagrelor, when used in patients with ACS and history of CVD, despite its more potent antithrombotic effect, has been demonstrated to reduce the incidence of ischemic events without a significant increase in hemorrhagic complications, leading to a favorable net clinical benefit compared to clopidogrel.…”