Efficacy and safety of ticagrelor versus prasugrel in smokers and nonsmokers with acute coronary syndromes

Background The efficacy and safety of ticagrelor versus prasugrel according to smoking status in patients with acute coronary syndromes (ACS) are not known. Purpose The aim of this study was to assess the efficacy and safety of ticagrelor versus prasugrel according to smoking status in patients with ACS undergoing invasive evaluation. Methods This pre-specified analysis of the ISAR-REACT 5 trial included 1349 smokers and 2652 nonsmokers randomised to receive ticagrelor or prasugrel. The primary endpoint was the incidence of death, myocardial infarction, or stroke; the secondary endpoint was the incidence of Bleeding Academic Research Consortium (BARC) type 3 to 5 bleeding. Both endpoints were assessed at 12 months after randomisation. Results There was no significant treatment arm-by-smoking status interaction regarding the efficacy outcome. The primary endpoint occurred in 47 patients (7.0%) in the ticagrelor group and 41 patients (6.2%) in the prasugrel group in smokers (hazard ratio [HR]=1.15; 95% confidence interval [CI] 0.76–1.75; P=0.510) and in 133 patients (10.2%) in the ticagrelor group and 94 patients (7.2%) in the prasugrel group in nonsmokers (HR=1.44 [1.10–1.87], P=0.007; Pint=0.378). The secondary endpoint occurred in 27 patients (4.6%) in the ticagrelor group and 33 patients (5.6%) in the prasugrel group in smokers (HR=0.81 [0.49–1.35]; P=0.412) and in 66 patients (6.0%) in the ticagrelor group and 46 patients (4.4%) in the prasugrel group in nonsmokers (HR=1.38 [0.94–2.01]; P=0.097). Conlusions Although there was no significant interaction between smoking and treatment effect, the present findings suggest a greater advantage of prasugrel over ticagrelor in nonsmoker vs. smoker patients with ACS. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): German Centre for Cardiovascular Research;Deutsches Herzzentrum München, Germany