One month of dual antiplatelet therapy (DAPT) reduced major bleeding events, without a significant increase in cardiovascular events, compared to 12-month DAPT after percutaneous coronary intervention (PCI), according to new trial data. The shorter regimen also was noninferior to standard DAPT, a pooled analysis of the STOPDAPT-2 trials shows. Yuki Obayashi, MD, and Ko Yamamoto, MD, both of the Kyoto University Graduate School of Medicine, Japan, presented these findings Friday at Transcatheter Cardiovascular Therapeutics (TCT) 2021 in Orlando, Florida. The STOPDAPT-2 ACS trial, which was presented in August at the European Society of Cardiology 2021 virtual congress, failed to show the noninferiority of 1-month DAPT with clopidogrel and aspirin, followed by 11 months of clopidogrel monotherapy, in comparison with 12-month DAPT in patients with acute coronary syndrome (ACS). The original STOPDAPT-2 trial, published in 2019, did establish both noninferiority and superiority of the shorter DAPT regimen to the standard regimen in terms of net clinical benefit. Both the original trial and STOPDAPT-2 ACS were underpowered, however, because event rates were lower than anticipated, Obayashi said Friday during his TCT presentation. Moreover, ACS presentation, patients with high bleeding risk (HBR) and the need for complex PCI are considered when clinicians decide on the duration of DAPT in real-world practice, he added. Therefore, the investigators sought to evaluate the safety and efficacy of clopidogrel monotherapy after 1 month of DAPT in the total STOPDAPT-2 cohort, pooling the populations of STOPDAPT-2 and STOPDAPT-2 ACS, and to explore the treatment-by-subgroup interaction for patients with ACS, HBR and the need for complex PCI. The primary endpoint in the pooled analysis was a composite of cardiovascular events (cardiovascular death, myocardial infarction, definite stent thrombosis or any stroke) and bleeding events (Thrombolysis in Myocardial Infarction [TIMI] major or minor bleeding). Secondary endpoints included the cardiovascular and bleeding endpoints. The rate of the primary composite endpoint was similar between the DAPT-duration groups (1-month DAPT 2.84% vs. 12-month DAPT 3.04%; hazard ratio [HR] 0.94; 95% confidence interval [CI] 0.70-1.27; log-rank p = 0.67). Shorter DAPT also demonstrated noninferiority (p for noninferiority = 0.001), but not superiority (p=0.68), to the longer regimen. The rate of the cardiovascular endpoint was also similar between the groups (short DAPT 2.4% vs. long DAPT 1.97%; HR 1.24; 95% CI 0.88-1.75). Bleeding was significantly lower in the short-DAPT group (0.5% vs. 1.31%; HR 0.38; 95% CI 0.21-0.70). An analysis of patients with ACS and those with chronic coronary syndrome (CCS) showed no difference in the primary and cardiovascular endpoints between the DAPT regimens. Bleeding was significantly lower in both the ACS and CCS subgroups on the shorter regimen (ACS: 1-month DAPT 0.54% vs. 12-month DAPT 1.17%, HR 0.46, 95% CI 0.23-0.94, p=0.03; CCS: 0.43% vs. 1.63%; HR 0.26; 95% CI 0.09-0.79, p=0.02), and there was nonsignificant interaction between these subgroups. Obayashi said the numerical increase in cardiovascular events in ACS patients on the shorter DAPT regimen warrants further studies of the optimal antithrombotic strategies for these patients. Similar patterns held in the HBR and non-complex PCI subgroups, but there was no significant difference in the bleeding endpoint between regimens among patients who underwent complex PCI or who were not HBR. Yamamoto noted that the absolute benefit of 1-month DAPT relative to 12-month DAPT was numerically greater in HBR patients (absolute difference, -1.61%) than in non-HBR patients (absolute difference, -0.42%). He added that given the lack of significant difference in the endpoints between DAPT regimens in the complex-PCI subgroup, “complex PCI might not be an appropriate determinant for DAPT duration after PCI.” The original STOPDAPT-2 trial was funded by Abbott Vascular, which did not supply the medications or devices, and the STOPDAPT-2 ACS trial was funded by Abbott Medical Japan.