Comparison of Clopidogrel Monotherapy After One to Two Months of Dual Antiplatelet Therapy With 12 Months of Dual Antiplatelet Therapy in Patients with Acute Coronary Syndrome The STOPDAPT-2 ACS Randomized Clinical Trial

Comparison of Clopidogrel Monotherapy After One to Two Months of Dual Antiplatelet Therapy With 12 Months of Dual Antiplatelet Therapy in Patients with Acute Coronary Syndrome The STOPDAPT-2 ACS Randomized Clinical Trial
Sabrina Wolfe, PharmD, Essentia Health

Background: Due to increasing concerns with bleeding events associated with prolonged dual antiplatelet therapy (DAPT), there is speculation over the idea of decreasing the duration of dual therapy. Specifically, this study was looking at acute coronary syndrome (ACS) patients for this extended therapy regimen. With limited recent comprehensive studies, this is an area to re-evaluate for safety and efficacy of extended treatment.

Purpose: This non-inferiority study looked at the safety and efficacy of DAPT for one to two months followed by clopidogrel as monotherapy versus 12 months of DAPT in patients with ACS.

Study Design: This multicenter study was completed in 96 centers around Japan between December 2015 through June 2020. Patients were randomly assigned to one of two open label treatment arms after receiving percutaneous coronary intervention (PCI): DAPT for one year or DAPT for one to two months with clopidogrel monotherapy continued for one year. Patients were assigned in a one-to-one stratified fashion.  Assessing a hazard ratio margin of 50% for cardiovascular events pertaining to cardiovascular death, myocardial infarction (MI), any stroke, or definite stent thrombosis or bleeding (major or minor) events at 12 months was the primary endpoint. The secondary endpoints assessed were cardiovascular and bleeding components related to the primary end point. Inclusion criteria was identical to the STOPDAPT-2 trial inclusion criteria with the addition of the following exclusion criteria: continued use of oral anticoagulants and previous history of hemorrhagic stroke. Stratification was done by the center before discharge from the hospital. Study group assignments were blinded to everyone: statisticians, members of the independent clinical event committee, steering committee, and Abbott Medical (the sponsor).

Results: Patients who were enrolled were noted to be younger with fewer comorbidities than patients who were not enrolled. A total of 4136 completed the study with an average age of 66.8 (11.9) years old and 856 (21%) were women. Patients were on clopidogrel (52%) or prasugrel (47%). At the one year clinical follow-up, the shorter duration of DAPT failed to prove  non-inferiority criteria when compared to those who completed a year of DAPT. Shorter duration of DAPT was associated with a reduction in major bleeding events. There was not a difference between these two arms when it came to primary and major secondary cardiovascular and bleeding end points. One to two months of DAPT was found to be inferior to a year of DAPT relating to the primary end point (absolute difference, 0.37% [95% CI −0.68% to 1.42%]; HR, 1.14 [95% CI 0.80-1.62]; P for non-inferiority = .06)

Conclusion: Shortened duration (one to two months) of DAPT failed to show non-inferiority when compared to the standard 12 month of DAPT for ACS patients post PCI. For now, there is not enough evidence to fully support using a shortened duration of DAPT for ACS patients and further clinical trials are needed.

Key Points/Clinical Impact:

  • One-to-two-months of DAPT did not demonstrate noninferiority to 12 months of DAPT for composite cardiovascular or bleeding events.
  • Shortened DAPT was associated with a reduction in major bleeding events but increased cardiovascular events.

References

  1. Watanabe H, Morimoto T, Natsuaki M et al. Comparison of Clopidogrel Monotherapy After 1 to 2 Months of Dual Antiplatelet Therapy With 12 Months of Dual Antiplatelet Therapy in Patients With Acute Coronary Syndrome. JAMA Cardiol. 2022;7(4):407. doi:10.1001/jamacardio.2021.5244