Reviwer: Dr. Emrah Erdoğan

Name of the Study: One-month Dual Antiplatelet Therapy Followed by Clopidogrel Monotherapy in Acute Coronary Syndrome: STOPDAPT-2 ACS Trial

Published Congress: ESC 2021

Link:

Background:

The current European guidelines recommend dual antiplatelet therapy (DAPT)  for at least 12 months after percutaneous coronary intervention(PCI) in acute coronary syndrome(ACS). Recent trials and meta-analyses demonstrated the benefit of very short DAPT (1-3M) and subsequent P2Y12i monotherapy in reducing bleeding without increasing cardiovascular events after ACS-PCI. However, the dominant strategy in these trials was monotherapy with newer P2Y12i after very short DAPT. So the benefit of very short DAPT and subsequent clopidogrel monotherapy is not addressed yet in ACS patients.

Objectives: 

The present study sought to explore the efficacy of 1-month of DAPT compared with the standard 12 months of DAPT after cobalt-chromium everolimus-eluting stent (CoCr-EES) implantation in patients with ACS.

Methods:

The STOPDAPT-2 ACS  trial was a multicenter, open-label, randomized clinical trial, designed to compare one month of DAPT and subsequent clopidogrel monotherapy with 12 months of DAPT after CoCr-EES implantation in patients with ACS. To generate sufficient statistical power, the STOPTDAPT-2 ACS trial enrolled 2988 ACS patients and pooled the results with the 1148 ACS patients in STOPDAPT-2 trial for a total of 4136 patients. Both trials used the same protocol. The primary endpoint was a composite of cardiovascular ( cardiovascular death, myocardial infarction, definite stent thrombosis, or any stroke)  and bleeding( TIMI major/minör bleeding)  events. The two major secondary endpoints were cardiovascular composite endpoint and bleeding endpoint at one year.  

Results:

Among 4169 patients randomized, 33 withdrew consent; of 4136 remaining completed the trial. One-month DAPT and subsequent clopidogrel therapy was failed to attest noninferiority to  12-month DAPT for the primary endpoint. The cumulative event rates of 3.2% in the 1-month DAPT group and 2.83% in the 12-month group were observed, which was not statistically different (HR 1.15; 95% CI 0.80-1.62). Moreover, while cumulative rates of TIMI major and minor bleeding were significantly lower with 1-month DAPT (0.54% vs 1.17%, HR 0.46; 95% CI: 0.23-0.94), the myocardial infarction rate was significantly higher (1.59% vs 0.85%, HR 1.91; 95% CI 1.06-3.44).

Conclusion:

Clopidogrel monotherapy after 1-month DAPT compared with standard 12-month DAPT failed to attest noninferiority for the primary endpoint.  There was a trend toward an increase in cardiovascular events despite a reduction in major bleeding events.

Interpretations:

While the rates of the primary endpoint, the major secondary CV endpoint, and major secondary bleeding endpoint all favored the shorter DAPT duration in the earlier STOPDAPT-2 trial (62% of patients had stable coronary artery disease and 38% had ACS), all three endpoints went in the opposite direction for STOPDAPT-2 ACS. Therefore in patients undergoing PCI for ACS, the totality of clinical evidence available continues to support 12-mont duration of DAPT as the preferred default approach.