Ticagrelor in the prevention of coronary and non-coronary atherothrombotic events: A comprehensive meta-analysis of 10 randomized trials

Background and aims: More potent antithrombotic strategies have significantly reduced the rate of recurrent ischemic events in cardiovascular disease. Ticagrelor, in particular, has significantly improved the outcome in patients with acute coronary syndromes, offering potential benefits also in terms of survival. In addition, more recent data have suggested that the advantages of ticagrelor could be extended also to non-coronary atherothrombotic disease, although with contrasting results, especially for mortality reduction. The aim of the present meta-analysis was to investigate the safety and effectiveness of a newer antiplatelet strategy with ticagrelor as compared to traditional antiplatelet regimens in patients with coronary or non-coronary atherothrombotic disease. Methods: Literature and main scientific session abstracts were searched for studies comparing a ticagrelor-based antiplatelet regimen vs. different antiplatelet agents in the secondary prevention of cardiac, cerebral or vascular atherothrombotic events. The primary efficacy endpoint was mortality, primary safety endpoint was the occurrence of major bleedings. Secondary endpoints were myocardial infarction and stroke. Results: We included 10 randomized clinical trials, for a total population of 73,121 patients, 54.9% randomized to ticagrelor. At a mean follow-up of 13.4 ± 12.6 months, a newer antiplatelet strategy based on ticagrelor was associated with a significant reduction in mortality as compared to a traditional therapy (OR[95%CI] = 0.92[0.86,0.99], p=0.02; phet = 0.14), however, such benefits were more evident in patients with coronary artery disease, while not in non-coronary trials, with a significant interaction between patients’ setting and the prognostic impact of ticagrelor (p int = 0.03). A similar result was achieved for cardiovascular mortality, recurrent myocardial infarction, while for the risk of stroke, the largest advantages were observed in patients with a previous cerebrovascular accident. Major bleeding events were increased in ticagrelor treated patients (OR [95%CI] = 1.11 [1.02, 1.20], p=0.01; phet = 0.0003), although not affecting overall mortality, as confirmed by meta-regression analysis. Conclusions: Based on the current meta-analysis, a newer antiplatelet strategy based on ticagrelor is associated with a significant reduction in mortality and recurrent cardiovascular events, as compared to a traditional treatment, among patients treated for coronary disease but not among those with non-coronary atherothrombotic disease. However, ticagrelor therapy was associated with a significant increase in major bleeding complications.