High bleeding risk patients with acute coronary syndromes treated with contemporary drug-eluting stents and Clopidogrel or Ticagrelor: Insights from CHANGE DAPT

Abstract Background The prospective observational CHANGE DAPT study compared clopidogrel versus ticagrelor-based dual antiplatelet (DAPT) regimens in consecutive patients with acute coronary syndrome (ACS), treated with percutaneous coronary intervention (PCI) with contemporary drug-eluting stents (DES). During the ticagrelor period (TP, May 2014–August 2015) there were more major bleedings than during the clopidogrel period (CP, December 2012–April 2014). Methods and results To evaluate whether the excess of major bleedings during TP may be limited to high bleeding risk (HBR) patients, we performed an explorative analysis of all 2062 CHANGE DAPT participants, of whom 547(26.5%) were classified as HBR (CP, n  = 245; TP, n  = 302). In HBR and non-HBR patients, we assessed the impact of CP versus TP on propensity score-adjusted rates of major bleeding and a pre-defined ischemic endpoint (composite of cardiac death, myocardial infarction, or stroke) at 1-year follow-up. Among HBR patients, the rate of major bleeding was significantly higher during TP (1.7% vs. 5.0%; HR adjusted 3.70 [95% CI 1.18–11.67], p  = 0.03), while there was no significant difference in the ischemic endpoint (6.6% vs. 8.0%, HR adjusted 1.23 [95% CI 0.63–2.42], p  = 0.54). In non-HBR patients, the rates of major bleeding (1.1% vs. 1.7%; HR adjusted 2.13 [95% CI 0.84–5.43], p  = 0.11) and the ischemic endpoint (2.8% vs. 3.4%, HR adjusted 1.38 [95% CI 0.74–2.57], p  = 0.32) were similar between both periods. Conclusions Among consecutive ACS patients, the increased risk of major bleeding during ticagrelor-based DAPT was limited to HBR patients. In both HBR and non-HBR patients, ticagrelor-based DAPT did not reduce ischemic outcomes following treatment with contemporary DES implantation.