| Summary: | The respective ischemic and bleeding risks of early aspirin discontinuation following an acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI) remain uncertain. We performed a prospero-registered review of randomized controlled trials (RCTs) comparing a P2Y<sub>12</sub> inhibitor-based single antiplatelet strategy following early aspirin discontinuation to a strategy of sustained dual antiplatelet therapy (DAPT) in ACS or PCI patients requiring, or not, anticoagulation for another indication (CRD42019139576). We estimated risk ratios (RR) and 95% confidence intervals (CI) using random effect models. We included nine RCTs comprising 40,621 patients. Compared to prolonged DAPT, major bleeding (2.2% vs. 2.8%; RR 0.68; 95% CI: 0.54 to 0.87; <i>p</i> = 0.002; I<sup>²</sup>: 63%), non-major bleeding (5.0 % vs. 6.1 %; RR: 0.66; 95% CI: 0.47 to 0.94; <i>p </i>= 0.02; I<sup>²</sup> : 87%) and all bleeding (7.4% vs. 9.9%; RR: 0.65; 95% CI: 0.53 to 0.79; <i>p</i> < 0.0001; I<sup>²</sup>: 88%) were significantly reduced with early aspirin discontinuation without significant difference for all-cause death (<i>p</i> = 0.60), major adverse cardiac and cerebrovascular events (MACE) (<i>p</i> = 0.60), myocardial infarction (MI) (<i>p</i> = 0.77), definite stent thrombosis (ST) (<i>p</i> = 0.63), and any stroke (<i>p</i> = 0.59). In patients on DAPT after an ACS or a PCI, early aspirin discontinuation prevents bleeding events with no significant adverse effect on the ischemic risk or mortality.
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