IMPORTANCE Very short mandatory dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with a drug-eluting stent may be an attractive option. OBJECTIVE To test the hypothesis of noninferiority of 1 month of DAPT compared with standard 12 months of DAPT for a composite end point of cardiovascular and bleeding events. DESIGN, SETTING, AND PARTICIPANTS Multicenter, open-label, randomized clinical trial enrolling 3045 patients who underwent PCI at 90 hospitals in Japan from December 2015 through December 2017. Final 1-year clinical follow-up was completed in January 2019. INTERVENTIONS Patients were randomized either to 1 month of DAPT followed by clopidogrel monotherapy (n=1523) or to 12 months of DAPT with aspirin and clopidogrel (n=1522). MAIN OUTCOMES AND MEASURES The primary end point was a composite of cardiovascular death, myocardial infarction (MI), ischemic or hemorrhagic stroke, definite stent thrombosis, or major or minor bleeding at 12 months, with a relative noninferiority margin of 50%. The major secondary cardiovascular end point was a composite of cardiovascular death, MI, ischemic or hemorrhagic stroke, or definite stent thrombosis and the major secondary bleeding end point was major or minor bleeding. RESULTS Among 3045 patients randomized, 36 withdrew consent; of 3009 remaining, 2974 (99%) completed the trial. One-month DAPT was both noninferior and superior to 12-month DAPT for the primary end point, occurring in 2.36% with 1-month DAPT and 3.70% with 12-month DAPT (absolute difference, −1.34% [95% CI, −2.57% to −0.11%]; hazard ratio [HR], 0.64 [95% CI, 0.42-0.98]), meeting criteria for noninferiority (P < .001) and for superiority (P = .04). The major secondary cardiovascular end point occurred in 1.96% with 1-month DAPT and 2.51% with 12-month DAPT (absolute difference, −0.55% [95% CI, −1.62% to 0.52%]; HR, 0.79 [95% CI, 0.49-1.29]), meeting criteria for noninferiority (P = .005) but not for superiority (P = .34). The major secondary bleeding end point occurred in 0.41% with 1-month DAPT and 1.54% with 12-month DAPT (absolute difference, −1.13% [95% CI, −1.84% to −0.42%]; HR, 0.26 [95% CI, 0.11-0.64]; P = .004 for superiority). CONCLUSIONS AND RELEVANCE Among patients undergoing PCI, 1 month of DAPT followed by clopidogrel monotherapy, compared with 12 months of DAPT with aspirin and clopidogrel, resulted in a significantly lower rate of a composite of cardiovascular and bleeding events, meeting criteria for both noninferiority and superiority. These findings suggest that a shorter duration of DAPT may provide benefit, although given study limitations, additional research is needed in other populations.

BackgroundPrediction of thrombotic and bleeding risk is important to optimize antithrombotic therapy after percutaneous coronary intervention.Methods and ResultsWe developed the prediction rules for thrombotic and bleeding events separately in Japanese patients. Derivation and validation cohorts consisted of 4778 patients from CREDO‐Kyoto (Coronary Revascularization Demonstrating Outcome Study in Kyoto) registry cohort 2 and 4669 patients from RESET (Randomized Evaluation of Sirolimus‐Eluting Versus Everolimus‐Eluting Stent Trial) and NEXT (Nobori Biolimus‐Eluting Versus Xience/Promus Everolimus‐Eluting Stent Trial). Primary thrombotic and bleeding events were a composite of myocardial infarction, definite or probable stent thrombosis or ischemic stroke, and GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) moderate or severe bleeding. The prediction rule for thrombosis assigned 2 points for severe chronic kidney disease, atrial fibrillation, peripheral vascular disease, and anemia and 1 point for age ≥75 years, heart failure, diabetes mellitus, and chronic total occlusion. The prediction rule for bleeding assigned 2 points for thrombocytopenia, severe chronic kidney disease, peripheral vascular disease, and heart failure and 1 point for prior myocardial infarction, malignancy, and atrial fibrillation. In derivation and validation cohorts, area under the curve was 0.68 and 0.64, respectively, for thrombosis and 0.66 and 0.66, respectively, for bleeding. In the validation cohort, a high thrombosis risk score (≥4, n=682) was associated with higher 3‐year incidence of thrombotic events than a score that was intermediate (2–3, n=1178) or low (0–1, n=2809) (7.6%, 3.7%, versus 2.4%, respectively; P<0.0001). A high bleeding risk score (≥3, n=666) was associated with higher incidence of bleeding than scores that were intermediate (1–2, n=1802) or low (0, n=2201) (8.8%, 4.1%, versus 2.3%, respectively; P<0.0001). Among 682 patients at high thrombotic risk, only 39 (5.7%) had low bleeding risk, whereas 401 (58.8%) had high bleeding risk with very high incidence of bleeding (11.6%).Conclusions CREDO‐Kyoto thrombotic and bleeding risk scores demonstrated modest accuracy in stratifying thrombotic and bleeding risks; however, a large proportion of patients at high thrombotic risk also had high bleeding risk.

Objective To assess the risks and benefits of P2Y 12 inhibitor monotherapy compared with dual antiplatelet therapy (DAPT) and whether these associations are modified by patients’ characteristics. Design Individual patient level meta-analysis of randomised controlled trials. Data sources Searches were conducted in Ovid Medline, Embase, and three websites ( www.tctmd.com , www.escardio.org , www.acc.org/cardiosourceplus ) from inception to 16 July 2020. The primary authors provided individual participant data. Eligibility criteria Randomised controlled trials comparing effects of oral P2Y 12 monotherapy and DAPT on centrally adjudicated endpoints after coronary revascularisation in patients without an indication for oral anticoagulation. Main outcome measures The primary outcome was a composite of all cause death, myocardial infarction, and stroke, tested for non-inferiority against a margin of 1.15 for the hazard ratio. The key safety endpoint was Bleeding Academic Research Consortium (BARC) type 3 or type 5 bleeding. Results The meta-analysis included data from six trials, including 24 096 patients. The primary outcome occurred in 283 (2.95%) patients with P2Y 12 inhibitor monotherapy and 315 (3.27%) with DAPT in the per protocol population (hazard ratio 0.93, 95% confidence interval 0.79 to 1.09; P=0.005 for non-inferiority; P=0.38 for superiority; τ 2 =0.00) and in 303 (2.94%) with P2Y 12 inhibitor monotherapy and 338 (3.36%) with DAPT in the intention to treat population (0.90, 0.77 to 1.05; P=0.18 for superiority; τ 2 =0.00). The treatment effect was consistent across all subgroups, except for sex (P for interaction=0.02), suggesting that P2Y 12 inhibitor monotherapy lowers the risk of the primary ischaemic endpoint in women (hazard ratio 0.64, 0.46 to 0.89) but not in men (1.00, 0.83 to 1.19). The risk of bleeding was lower with P2Y 12 inhibitor monotherapy than with DAPT (97 (0.89%) v 197 (1.83%); hazard ratio 0.49, 0.39 to 0.63; P<0.001; τ 2 =0.03), which was consistent across subgroups, except for type of P2Y 12 inhibitor (P for interaction=0.02), suggesting greater benefit when a newer P2Y 12 inhibitor rather than clopidogrel was part of the DAPT regimen. Conclusions P2Y 12 inhibitor monotherapy was associated with a similar risk of death, myocardial infarction, or stroke, with evidence that this association may be modified by sex, and a lower bleeding risk compared with DAPT. Registration PROSPERO CRD42020176853.

Background: Recently, the Academic Research Consortium for High Bleeding Risk (ARC-HBR) has been proposed to standardize the definition of HBR, which was arbitrarily defined as a Bleeding Academic Research Consortium 3 or 5 bleeding ≥4% at 1-year. However, the prevalence and the expected bleeding event rate of HBR patients defined by ARC-HBR criteria are currently unknown in the real-world percutaneous coronary intervention practice. Methods: We applied the ARC-HBR criteria in the CREDO-Kyoto (Coronary Revascularization Demonstrating Outcome Study in Kyoto) registry cohort-2, a multicenter registry that enrolled 13 058 consecutive patients who underwent their first percutaneous coronary intervention. The primary bleeding end point was defined as the Global Utilization of Streptokinase and Tissue plasminogen activator for Occluded coronary arteries moderate/severe bleeding. There were 5570 patients (43%) in the HBR group and 7488 patients in the no-HBR group. Results: Cumulative incidence of the primary bleeding end point was much higher in the HBR group than in the no-HBR group (10.4% versus 3.4% at 1-year, and 18.9% versus 6.6% at 5-year, P <0.0001). Presence of each ARC-HBR major or even minor criterion, in isolation, with the exception of liver cirrhosis and prior ischemic stroke, was also associated with major bleeding risk higher than 4% at 1-year. Cumulative 5-year incidence of the primary bleeding end point got incrementally higher as the number of the ARC-HBR major criteria increased (≥3 majors: 49.9%, 2 majors: 30.6%, 1 major: 18.5%, ≥2 minors: 14.7%, and no-HBR: 6.6%, P <0.0001). Conclusions: ARC-HBR criteria successfully identified those patients with very HBR after percutaneous coronary intervention, who represented 43% of patients in this all-comers registry.

IMPORTANCEClopidogrel monotherapy after short dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) has not yet been fully investigated in patients with acute coronary syndrome (ACS).OBJECTIVE To test the hypothesis of noninferiority of 1 to 2 months of DAPT compared with 12 months of DAPT for a composite end point of cardiovascular and bleeding events in patients with ACS. DESIGN, SETTING, AND PARTICIPANTSThis multicenter, open-label, randomized clinical trial enrolled 4169 patients with ACS who underwent successful PCI using cobalt-chromium everolimus-eluting stents at 96 centers in Japan from December 2015 through June 2020. These data were analyzed from June to July 2021.INTERVENTIONS Patients were randomized either to 1 to 2 months of DAPT followed by clopidogrel monotherapy (n = 2078) or to 12 months of DAPT with aspirin and clopidogrel (n = 2091). MAIN OUTCOMES AND MEASURESThe primary end point was a composite of cardiovascular (cardiovascular death, myocardial infarction [MI], any stroke, or definite stent thrombosis) or bleeding (Thrombolysis in MI major or minor bleeding) events at 12 months, with a noninferiority margin of 50% on the hazard ratio (HR) scale. The major secondary end points were cardiovascular and bleeding components of the primary end point. RESULTS Among 4169 randomized patients, 33 withdrew consent. Of the 4136 included patients, the mean (SD) age was 66.8 (11.9) years, and 856 (21%) were women, 2324 (56%) had ST-segment elevation MI, and 826 (20%) had non-ST-segment elevation MI. A total of 4107 patients (99.3%) completed the 1-year follow-up in June 2021. One to 2 months of DAPT was not noninferior to 12 months of DAPT for the primary end point, which occurred in 65 of 2058 patients (3.2%) in the 1-to 2-month DAPT group and in 58 of 2057 patients (2.8%) in the 12-month DAPT group (absolute difference, 0.37% [95% CI, −0.68% to 1.42%]; HR, 1.14 [95% CI, 0.80-1.62]; P for noninferiority = .06). The major secondary cardiovascular end point occurred in 56 patients (2.8%) in the 1-to 2-month DAPT group and in 38 patients (1.9%) in the 12-month DAPT group (absolute difference, 0.90% [95% CI, −0.02% to 1.82%]; HR, 1.50 [95% CI, 0.99-2.26]). The major secondary bleeding end point occurred in 11 patients (0.5%) in the 1to 2-month DAPT group and 24 patients (1.2%) in the 12-month DAPT group (absolute difference, −0.63% [95% CI, −1.20% to −0.06%]; HR, 0.46 [95% CI, 0.23-0.94]). CONCLUSIONS AND RELEVANCEIn patients with ACS with successful PCI, clopidogrel monotherapy after 1 to 2 months of DAPT failed to attest noninferiority to standard 12 months of DAPT for the net clinical benefit with a numerical increase in cardiovascular events despite reduction in bleeding events. The directionally different efficacy and safety outcomes indicate the need for further clinical trials.