Ticagrelor as compared to conventional antiplatelet agents in coronary artery disease: A comprehensive meta-analysis of 15 randomized trials

Background: Ticagrelor has been shown to offer potential outcome benefits in acute coronary syndromes and for the long-term cardiovascular prevention, reducing mortality and the recurrence of ischemic events. However, data from real-world and recent meta-analyses have suggested that the anti-ischemic benefits of ticagrelor could be lower than expected, potentially outweighed by an increased risk of bleeding complications. Therefore, the aim of the present meta-analysis was to evaluate the prognostic impact of ticagrelor as compared to the conventional antiplatelet agents (ASA and clopidogrel) in patients with coronary artery disease (CAD), enclosing patients with acute coronary syndromes and stable CAD. Methods: Literature and main scientific session abstracts were searched for studies comparing a ticagrelor-based antiplatelet regimen vs different antiplatelet agents in patients with CAD. The primary efficacy endpoint was mortality, and the primary safety endpoint was the occurrence of major bleedings. Secondary endpoints were cardiovascular mortality, myocardial infarction, stroke and intracranial hemorrhage (ICH). Results: We included 15 randomized clinical trials, with a total population of 73,402 patients (55% randomized to ticagrelor). At a mean follow-up of 15 ± 11.3 months, the ticagrelor based strategy did not significantly reduce mortality as compared to the traditional therapy (OR[95%CI] = 0.88[0.70,1.09], p = 0.24; phet<0.00001), with comparable results and no interaction according to patients' presentation (p interaction = 0.80). A similar result was achieved for cardiovascular mortality, whereas the reduction of recurrent myocardial infarction was significant (OR[95%CI] = 0.84[0.78,0.90], p < 0.00001; phet = 0.76). As for the risk of stroke, the largest reduction was observed in stable patients, while a neutral effect was observed in the ACS subgroup (p int = 0.35). Major bleeding events were increased in ticagrelor-treated patients (OR [95%CI] = 1.40 [1.06, 1.84], p = 0.02; phet<0.00001), especially ICH (OR [95% CI] = 1.45[1.13,1.84], p = 0.003; phet = 0.93), and mainly among non-ACS patient. No interaction for any outcome endpoint was observed according to patients' age. Conclusions: Based on the current meta-analysis, a ticagrelor-based strategy for the treatment of patients with coronary artery disease is associated to a significant increase in major bleeding complications and especially for intracranial hemorrhage, as compared to a strategy based on conventional antiplatelet agents, while resulting in a neutral effect on survival. However, a significant reduction of recurrent myocardial infarction was observed with ticagrelor.