Canadian Journal of Cardiology



      Various approaches to dual antiplatelet therapy (DAPT) management exist to balance thrombotic and bleeding risks following acute coronary syndrome (ACS). The aim of this study was to compare and rank different DAPT management strategies in patients with ACS with or without percutaneous coronary intervention (PCI).

      Methods and Results

      We conducted a systematic review with network meta-analysis of randomized controlled trials (RCTs) comparing DAPT strategies in patients with ACS. We searched MEDLINE, Embase, and CENTRAL (2007-July 2021) for RCTs that enrolled patients with ACS (or PCI with outcomes reported separately for ACS subgroup) comparing ≥2 DAPT strategies, including comparisons between P2Y12 inhibitors, empiric P2Y12 inhibitor de-escalation (switching from prasugrel- or ticagrelor-based DAPT after 1 month to clopidogrel-based DAPT to complete 12 months DAPT duration), pharmacogenomic- or platelet-function testing-guided P2Y12 inhibitor selection, or short-duration DAPT (1-3 months of DAPT followed by P2Y12 inhibitor monotherapy) with intended follow-up ≥12 months. The primary outcome was major adverse cardiovascular events (MACE). Secondary outcomes included all-cause death and major bleeding. We performed Bayesian network meta-analyses to compare all interventions simultaneously using the Markov-chain Monte Carlo method, conducted under the assumption of transitivity. We generated odds ratios (ORs) with 95% credible intervals (CrI) from the medians and 2.5th and 97.5th percentiles of the posterior distributions using a hierarchical Bayesian framework, using a random-effects model with informative priors for between-study heterogeneity based on pharmacological interventions with semi-objective outcomes (MACE or bleeding) or death. To rank interventions for each outcome, we calculated the mean surface under the cumulative ranking (SUCRA) curve. From 5941 articles, we included 24 RCTs enrolling 89,620 patients. Both clopidogrel- and ticagrelor-based DAPT increased MACE compared with pharmacogenomics-guided P2Y12 inhibitor selection (odds ratio [OR] 1.37, 95% credible interval [CrI] 1.08-1.74 and 1.35, 1.05-1.79, respectively) and empiric P2Y12 inhibitor de-escalation (OR 1.53, 95% CrI 1.00-2.30 and 1.51, 1.00-2.27, respectively). Compared with short-duration DAPT, standard DAPT duration with all P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor) and pharmacogenomics-guided P2Y12 inhibitor selection increased major bleeding. Ticagrelor-based DAPT increased major bleeding compared with platelet function testing-guided DAPT (OR 1.60, 95% CrI 1.00-2.55). Empiric P2Y12 inhibitor de-escalation ranked best for MACE (SUCRA 0.89), whereas short-duration DAPT ranked best for death (SUCRA 0.89) and major bleeding (SUCRA 0.93).