Effect of 1-Month Dual Antiplatelet Therapy Followed by Clopidogrel vs 12-Month Dual Antiplatelet Therapy on Cardiovascular and Bleeding Events in Patients Receiving PCI

Abstract

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.

Platelet Function Test Use for Patients with Coronary Artery Disease in the Early 2020s

“…The primary endpoint (bleeding events) occurred less frequently in the monotherapy arm than in the DAPT arm (hazard ratio = 0.56, 95% CI 0.45-0.68, p < 0.001), with no difference in ischemic endpoints (p < 0.001 for non-inferiority). This strategy of short, uniform de-escalation, irrespective of PFT results, has also been supported by other recent trials involving several thousand patients and showing that rapid de-escalation of antiplatelet therapy was effective and associated with fewer bleeding events after ACS, including STEMI [75,76].…”

The efficacy and safety of P2Y12 inhibitor monotherapy in patients after percutaneous coronary intervention

“…As described in Figure 1 patients met our eligibility criteria. [11][12][13][14] Of these, 14 530 patients were randomized to monotherapy with a P2Y12 inhibitor, whereas 14 599 patients were randomized to standard dual antiplatelet therapy. Four trials tested P2Y12 inhibitor monotherapy after 1 to 3 month of DAPT vs P2Y12 inhibitor plus aspirin ( Table 1).…”

“…The findings of the SMART-CHOICE trial and the STOPDAPT-2 trial showed that monotherapy with a P2Y12 inhibitor after shortduration dual antiplatelet therapy was noninferior to 12-month DAPT in the Asian patients who were at lower risk for ischemic events. 12,13 There was no restriction on the type of P2Y12 inhibitors in the SMART-CHOICE trial. On the contrary, the STOPDAPT-2 trial is limited by the exclusive use of clopidogrel.…”

Early Aspirin Discontinuation Following Acute Coronary Syndrome or Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…In these circumstances, the benefit of sustained DAPT may translate into a smaller absolute ischemic event risk reduction, which might be potentially outweighed by the associated higher risk of bleeding [6]. Since aspirin yields limited additional platelet inhibition when associated with P2Y 12 inhibitors, aspirin-free strategies have been evaluated in several recent randomized controlled trials enrolling ACS or PCI patients; in some of these studies patients also had an indication for chronic oral anticoagulation (OAC) [7][8][9][10][11][12][13][14][15][16][17][18][19]. Most of these trials (but not all) reported lower rates of bleeding without aspirin, but all of them were underpowered as to properly evaluate the associated ischemic risk.…”