Abatement of potent P2Y12 antagonist-based dual antiplatelet therapy after coronary intervention: A network meta-analysis of randomized controlled trials

INTRODUCTION: Dual antiplatelet therapy (DAPT) including prasugrel or ticagrelor is recommended in patients with acute coronary syndromes (ACS) treated with coronary intervention (PCI). Acknowledging the importance of bleeding, multiple trials tested abatement schemes including uniform or guided de-escalation from the potent P2Y12 inhibitor (P2Y12-De) or P2Y12 inhibitor monotherapy (P2Y12-Mo) with heterogeneous results. We aimed to perform a systematic review and network meta-analysis of the impact of DAPT abatement strategies in patients with PCI. METHODS: Electronic databases were searched for relevant randomized clinical studies evaluating clinical outcomes of patients after PCI. The rate of adverse events was evaluated using a frequentist network metanalysis. The random-effects model was used to combine risk estimates across trials and risk ratio (RR) with 95% confidence intervals (95% CIs) served as summary statistics. The primary endpoints of interest were the rate of major cardiac adverse events (MACE, defined as the composite of cardiovascular mortality, myocardial infarction and stroke) and bleeding. RESULTS: Ten studies were identified randomizing 42511 patients. 6359 switched to the P2Y12-De and 13062 switched to the P2Y12-Mo. The risk of MACE, reflected a 24% reduction in the P2Y12-De and a 14% in the P2Y12-Mo in comparison with the DAPT strategy using potent P2Y12 inhibitors (RR: 0.76 [0.62, 0.94], and RR: 0.86 [0.75, 0.99], p < 0.05 both). A 35% risk reduction of major bleeding was seen with monotherapy (RR: 0.65 [0.46, 0.91],) contrasting the de-escalation trials where this effect was not significant (RR: 0.84 [0.57, 1.22]). All bleeding and minor bleeding events were reduced with both strategies. Indirect P2Y12-Mo versus P2Y12-De comparisons exhibited them as similar alternatives without significant differences. CONCLUSION: Our analysis suggests that both P2Y12-De and P2Y12-Mo reduce ischemic events and bleeding among PCI-treated ACS patients. Ischemic benefit was more expressed with P2Y12-De, however, reduction of major bleeding was only significant with P2Y12-Mo strategy. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021258502, identifier CRD42021258502.