Ticagrelor Compared to Clopidogrel in aCute Coronary syndromes (TC4) – A Bayesian pragmatic cluster randomized controlled trial

Background Dual-antiplatelet therapy (DAPT) is the standard of care for acute coronary syndromes, but uncertainty exists regarding the optimal regime for North American patients. Methods This pragmatic, open-label, time clustered, randomized trial ( ClinicalTrials.Gov ( NCT04057300 ) compared the effectiveness and safety of DAPT with ticagrelor or clopidogrel in acute coronary syndrome patients from a single tertiary academic center in Montreal, Canada. The primary effectiveness endpoint was a composite of all-cause mortality, non-fatal myocardial infarction, or ischemic stroke. The primary safety endpoint were bleeding hospitalizations. Twelve-month outcomes were ascertained from the Québec universal electronic health databases. The study was designed and analyzed within a Bayesian paradigm to supplement existing knowledge. The primary analysis was a Bayesian logistic regression models with an informed focused prior from previously randomized North American patients. Robustness was evaluated with vague and other pre-specified informative priors, spanning reasonable pre-existing beliefs. Clinically significant benefits and harms were defined as risk reductions exceeding a 10% difference. Results 1,005 ACS patients were randomized to ticagrelor (n = 450) or clopidogrel (n = 555). MACE occurred in 50 (11.1%) ticagrelor and 64 (11.5%) clopidogrel patients (relative risk (RR), 0.95; 95% credible interval [95% CrI]: 0.67, 1.35 with a vague prior). The primary analysis with an informed focused prior resulted in probabilities of a clinically meaningful ticagrelor benefit (RR<0.9), equivalence (0.9 ≦ RR ≧, 1.1) or harm (RR ≧, 1.1) of 2%, 41% and 57%, respectively. For the safety endpoint, there was no consistent signal of benefit or harm with ticagrelor. Sensitivity analyses with a range of prior beliefs gave generally consistent results. Conclusions Whether this trial was analysed with a vague, or a range of reasonable informed priors, no strong evidence for the superiority of ticagrelor over clopidogrel was found.