Risk of bradyarrhythmia related to ticagrelor: A systematic review and meta-analysis.

CONTEXT: Ticagrelor was related to bradycardia in DISPERSE-II trial. This risk has been integrated into the European risk-management plan, and its use is warned in at-risk patients. Nevertheless, this risk was not systematically assessed nor measured. OBJECTIVES: To estimate the risk of bradyarrhythmia associated with ticagrelor. STUDY DESIGN: Systematic review and meta-analysis. DATA-SOURCE: MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, ISI web of Science, clinicaltrial.gov, clinicaltrialsregister.eu. STUDY SELECTION: Randomized controlled trials (RCTs) and observational studies in patients treated with ticagrelor or comparator(s). META-ANALYSIS: Risk of bias in each RCT was assessed using Cochrane tool. Relative Risks (RR) with 95 % confidence intervals (95 %CI) were calculated for each RCT, and pooled using fixed-effect or random-effects models, when appropriate. Subgroup and sensitivity analyses were performed. A potential publication bias was searched. RESULTS: Among 82 eligible studies, event data were missing for 56 studies, due to detected reporting bias (i.e. inability to confirm zero events). Fifteen RCTs were selected and the combined RR of bradyarrhythmia was 1.15 (95 %CI 1.05-1.26), and 1.29 (1.02-1.65) for severe bradyarrhythmia. The risk appeared to be dose dependent. Restricting the analysis only to RCTs performed in patients without previous bradyarrhythmia resulted in a non-increased risk. CONCLUSION: This meta-analysis confirmed the risk of bradyarrhythmia or severe bradyarrhythmia related to ticagrelor, and its use in patients without previous bradycardia was effective in preventing it. The evidence coming from this meta-analysis was low to moderate due to missing outcome in 2/3 of eligible studies. Waiting for access to these data, the use of ticagrelor in patients with risk factors of bradycardias should be avoided.