Network meta-analysis and trial sequential analysis for atrial fibrillation patients receiving PCI or with ACS

Fig. 1. The antithrombotic strategies investigated in the NMA of randomized controlled trials for patients with AF with ACS or undergoing PCI. For each of these strategies, direct comparisons were made with previous trials, and NMA could further provide indirect comparisons to estimate the relative risk of the efficacy and safety outcomes. AF = atrial fibrillation; ACS = acute coronary syndrome; DAPT = dual antiplatelet therapy; NMA = network meta-analysis; NOAC = nonvitamin K oral anticoagulant; PCI = percutaneous coronary intervention; VKA = vitamin K antagonist.

Fig. 2. Forest plots for network comparison of the safety and efficacy outcomes. For each outcome, VKA + DAPT is the reference group. The odds ratio obtained from NMA is presented for different antithrombotic strategies, compared with VKA + DAPT. DAPT = dual antiplatelet therapy; NOAC = nonvitamin K oral anticoagulant; VKA = vitamin K antagonist.

Fig. 3. Pairwise meta-analysis and TSA of five trials evaluating the efficacy and safety of DAT against TAT. For TSA, the required information size (RIS) was calculated using different assumptions of the relative risk reduction (RRR) or relative risk increase (RRI), control event rate (CER), and model-estimated diversity for each outcome. We used an anticipated RRR of 35% for the safety outcomes and an RRI of 10% for cardiovascular death, 20% for myocardial infarction, and 35% for stent thrombosis. The cumulative Z curve (bold solid line) was constructed using a random effects model. The horizontal dashed line at cumulative Z = ± 1.96 indicates a conventional level of statistical significance. The converging dotted line and the divergent dotted line represent the trial sequential significance boundary and futility boundary, respectively. These monitoring boundaries were constructed based on the O’Brien-Fleming method. D = diversity; DAT = dual antithrombotic therapy; M-H = Mantel-Haenszel; TAT = triple antithrombotic therapy; TSA = trial sequential analysis.

Fig. 4. Dual vs. Triple antithrombotic therapy (DAT vs. TAT) for the safety and efficacy outcomes in patients with atrial fibrillation with acute coronary syndrome or undergoing percutaneous coronary intervention.