The risk of dyspnea in patients treated with third-generation P2Y12 inhibitors compared with clopidogrel: a meta-analysis of randomized controlled trials

Background Ticagrelor and prasugrel are two third-generation oral P2Y 12 inhibitors which are more commonly used in clinical practice. However, dyspnea has been consecutively reported in patients using third-generation oral P2Y 12 inhibitors. This study aims to compare the risk of dyspnea in patients treated with third-generation P2Y 12 inhibitors compared with clopidogrel. Methods We systematically searched the PubMed, Cochrane Central Register of Controlled Trials databases, ClinicalTrials.gov and Web of Science for randomized control trials (RCTs) comparing ticagrelor or prasugrel with clopidogrel until July 2019. The primary outcome was the incidence of dyspnea. The risk ratios (RR) and 95% confidence intervals (CI) were estimated using meta-analysis. Results We included 25 RCTs involving 63,484 patients in this meta-analysis, including 21 studies on ticagrelor and 4 studies on prasugrel. Compared to the clopidogrel group, third-generation oral P2Y 12 inhibitors were associated with an increased risk of dyspnea compared with clopidogrel (RR 2.15, 95% CI 1.59–2.92), which was consistent in the analysis of ticagrelor (RR 2.65, 95% CI 1.87–3.76). However, the adverse effect was not found among patients receiving prasugrel therapy (RR 1.03, 95% CI 0.86–1.22). The increased dyspnea risk of ticagrelor was consistent in subgroups with different follow-up durations (≤ 1 month RR 1.87, 95% CI 1.56–2.24; 1–6 months RR 4.19, 95% CI 1.99–8.86; > 6 months 2.45, 95% CI 1.13–5.34). Conclusions Ticagrelor has a higher risk of dyspnea than clopidogrel, which was not observed in patients using prasugrel.