P6411Dyspnea in ticagrelor treated patients in the all-comer randomized GLOBAL LEADERS study and its association with clinical outcomes

Background Dyspnea represents a drug adverse effect reported with a higher frequency for ticagrelor, as compared with other P2Y12 antagonists. The impact of dyspnea on clinical outcomes has not been yet evaluated in the context of aspirin-free therapies after percutaneous coronary intervention (PCI). Purpose The study aimed to evaluate the incidence of dyspnea and its associations with demographic characteristics and clinical outcomes in patients undergoing PCI treated with ticagrelor either as monotherapy or as a part of a dual antiplatelet therapy (DAPT) in the GLOBAL LEADERS cohort. Methods This is a sub-analysis of the randomized all-comer GLOBAL LEADERS study (n=15991), comparing the experimental strategy of ticagrelor monotherapy following one-month DAPT after PCI with the reference strategy of 12-month DAPT followed by 12-month aspirin monotherapy. The incidence of dyspnea reported as adverse event (AE) and its relation to demographic characteristics and 2-year clinical outcomes was evaluated (intention-to-treat analysis). Multivariable Cox proportional hazards models were performed, including randomized treatment and incidence of first dyspnea event as a time-dependent covariate. The primary endpoint was a composite of 2-year all-cause mortality or centrally adjudicated, new Q-wave myocardial infarction (MI). Patient-oriented clinical endpoints (POCE) comprised all-cause death, any stroke, MI or revascularization, whereas net adverse clinical events (NACE) included POCE and Bleeding Academic Research Consortium (BARC)-defined bleeding type 3 or 5. Results Overall, dyspnea was reported as an AE in 2101 patients (13.2%) up to two years of follow-up, with a higher frequency in the experimental arm (16.4%) as compared with the reference group (11.1%) (hazard ratio [HR]1.70, 95% confidence interval [CI] 1.56–1.86, p=0.001). Predictors of dyspnea AE up to 2 years by multivariate analyses were: chronic obstructive pulmonary disease (HR1.71, 95% CI 1.56–1.87, p=0.001), female gender (HR1.31, 95% CI 1.18–1.44, p=0.001), hypertension (HR1.31, 95% CI 1.19–1.44, p=0.001, prior coronary artery bypass grafting (HR1.30, 95% CI 1.10–1.54, p=0.003), left ventricle ejection fraction below 40% (HR1.22, 95% CI 1.04–1.42, p=0.012), presentation with acute coronary syndrome (HR1.19, 95% CI 1.09–1.29, p=0.001) and body mass index (≥27kg/m2) (HR1.17, 95% CI 1.08–1.28, p=0.001). In patients who reported dyspnea AE, the two-year rates of the efficacy and safety endpoints in the experimental and reference arm were: for the primary endpoint 3.4% vs. 4.3% (p adjusted=0.807), for POCE 15.8% vs. 17.6% (p adjusted=0.218), for NACE 17.2% vs. 19.6% (p adjusted=0.082), for BARC 3 or 5 type bleeding 17.2% vs. 19.6% (p adjusted=0.082), respectively. Conclusions The occurrence of dyspnea AE up to two years after PCI appeared not to affect the safety of the experimental treatment strategy of 23-month ticagrelor monotherapy following one-month DAPT after PCI. Acknowledgement/Funding Study founded by European Cardiovascular Research Institute, which received unrestricted grants from Biosensors Int., AstraZeneca, Medicines Company.