Controversy remains regarding the optimal antiplatelet regimen in patients with
acute coronary syndrome (ACS). This study sought to investigate the efficacy and safety of P2Y12 inhibitor monotherapy compared with conventional dual antiplatelet
therapy (
DAPT) and
aspirin monotherapy in patients with ACS undergoing
percutaneous coronary intervention. Data on 4,453 patients were pooled from SMART-DATE and SMART-CHOICE randomized trials. Antiplatelet
therapy regimens were categorized as P2Y12 inhibitor monotherapy (P2Y12 inhibitor monotherapy after 3-month
DAPT), conventional
DAPT (12-month or longer
DAPT), and
aspirin monotherapy (
aspirin monotherapy after 6-month
DAPT). The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE, a composite of all-cause death,
myocardial infarction, and
stroke). Inverse-probability of treatment-weighted (IPTW) analysis was performed. At 1 year, patients in the P2Y12 inhibitor monotherapy had a comparable risk of MACCE compared with those in the conventional
DAPT (IPTW-adjusted hazard ratio [HR], 0.655; 95% confidence interval [CI] 0.393 to 1.094; p = 0.106), and tended to have a lower risk of MACCE than those in the
aspirin monotherapy (IPTW-adjusted HR, 0.606; 95% CI, 0.347 to 1.058; p = 0.078). The adjusted hazard for the
Bleeding Academic Research Consortium (BARC) type 2 to 5
bleeding was significantly lower in P2Y12 inhibitor monotherapy than in conventional
DAPT (IPTW-adjusted HR, 0.341; 95% CI, 0.190 to 0.614; p < 0.001) and in
aspirin monotherapy (IPTW-adjusted HR, 0.359; 95% CI, 0.182 to 0.708; p = 0.003). In conclusion, among patients with ACS undergoing PCI, P2Y12 inhibitor monotherapy after 3-month
DAPT reduced risk of
bleeding compared with conventional
DAPT and
aspirin monotherapy after 6-month
DAPT without increasing MACCE.