title: Network meta-analysis of prasugrel, ticagrelor, high- and standard-dose clopidogrel in patients scheduled for percutaneous coronary interventions.
abstract: Since novel antiplatelet treatments (prasugrel, ticagrelor, high-dose clopidogrel) have been predominantly tested against standard-dose clopidogrel, data on direct comparisons between these therapies are scarce. We therefore indirectly compared their efficacy and safety in patients undergoing percutaneous coronary intervention. Electronic databases were searched systematically to identify head-to-head randomised controlled trials (RCTs). Network meta-analysis was performed using generalised linear mixed models with adjustment for length of follow-up. Findings were corroborated by mixed treatment comparison through Bayesian methods. Fourteen RCTs were identified and included in the analysis (high- vs. standard-dose clopidogrel: 9 trials, prasugrel vs. high-dose clopidogrel: 2 trials, prasugrel vs. standard-dose clopidogrel: 2 trials, ticagrelor vs. standard-dose clopidogrel: 1 trial). No significant differences were found for efficacy outcomes except for stent thrombosis favouring prasugrel (vs. ticagrelor: odds ratio [OR] 0.63, 95% confidence interval [CI]: 0.42, 0.94; vs. high-dose clopidogrel: OR 0.70, 95%CI: 0.48, 1.01). Prasugrel exhibited a similar bleeding risk as high-dose clopidogrel, but more major (OR 1.43, 95%CI 1.07, 1.90) and major or minor bleeding (OR 1.36, 95%CI 1.09, 1.69) compared to ticagrelor. Ticagrelor was also associated with less major or minor bleeding compared to high-dose clopidogrel (OR 0.81, 95%CI 0.69, 0.96). No differences were seen for non CABG-related major bleeding between the three strategies. Results were corroborated in a subgroup analysis comprising only patients with acute coronary syndromes. In the absence of head-to-head clinical trials, network meta-analysis suggests potentially relevant differences in efficacy and bleeding risk among novel antiplatelet treatments and may thereby advance understanding of their differential therapeutic properties.
authors.affiliation: Department of Internal Medicine II, Division of Angiology, Medical University Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. sabine.m.steiner@meduniwien.ac.at
authors.forename: Sabine
authors.initials: S
authors.lastname: Steiner
authors.forename: Deddo
authors.initials: D
authors.lastname: Moertl
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Doug
authors.initials: D
authors.lastname: Coyle
authors.forename: George A
authors.initials: GA
authors.lastname: Wells
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy; D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D017130:Angioplasty / Q000379:methods; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D000077144:Clopidogrel; D006470:Hemorrhage; D006801:Humans; D016017:Odds Ratio; D062645:Percutaneous Coronary Intervention / Q000379:methods*; D010879:Piperazines / Q000008:administration & dosage*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D000068799:Prasugrel Hydrochloride; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D015607:Stents; D013876:Thiophenes / Q000008:administration & dosage*; D000077486:Ticagrelor; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D013876:Thiophenes; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine