Despite advances in therapy, the choice and duration of antiplatelet therapy following percutaneous coronary intervention (PCI) remains an area of active debate. While it has been postulated that long-term dual antiplatelet therapy (DAPT) are associated with reduced rates of thrombotic events, these benefits have been offset by increased bleeding risk.
In the initial STOPDAPT-2 trial, which included patients with stable coronary artery disease (CAD) and with acute coronary syndrome (ACS) undergoing PCI, a strategy of 1 month of dual antiplatelet therapy (DAPT) followed by clopidogrel monotherapy was associated with significant reduction in the composite of cardiovascular and bleeding events when compared to standard-of-care 12 months of DAPT. While the net clinical benefit was observed in the overall population, the trial was not sufficiently powered to compare the effect of the 2 treatment strategies among ACS patients alone.
To address this concern, the subsequent STOPDAPT-2 ACS trial, which was protocoled in a similar fashion to the original STOPDAPT-2 trial, enrolled exclusively ACS patients. Notably, the trial was designed to demonstrate, with sufficient statistical power, the safety and efficacy of a 1-month DAPT strategy followed by clopidogrel monotherapy. Nonetheless, while the initial STOPDAPT-2 trial demonstrated non-inferiority and superiority of 1-month DAPT, its sister ACS trial fell short for the same primary endpoint and failed to match the original results.
The present pooled analysis combined the total cohort of ACS patients, who were enrolled in both the original STOPDAPT-2 trial and the subsequent STOPDAPT-2 ACS trial. A total of nearly 6,000 patients were included, one-third of whom were considered of high-bleeding risk. The primary endpoint was the combination of thrombotic and bleeding outcomes, namely CV death, MI, stent thrombosis, and TIMI major/minor bleeding.
The total cohort analysis of STOPDAPT-2 was presented as a late-breaking clinical trial at TCT 2021 in Orlando, FL in a joint presentation by Dr. Yuki Obayashi, MD and Dr. Ko Yamamoto (Kyoto University Hospital, Japan). Compared with 12 months of DAPT, there was a numerical increase in the rate of CV thrombotic events in the 1-month DAPT group, but notably this increase did not reach statistical significance, and the 2 strategies were therefore considered non-inferior to one another. With regards to bleeding risk, the 1-month DAPT strategy – as expected – was associated with significantly fewer major bleeding events. Furthermore, subgroup analyses, particularly high-bleeding risk status and PCI complexity, demonstrated no significant variation compared to the the overall findings.
According to the investigators, the non-inferiority observed with 1-month DAPT with regards to CV events was, at least in part, attributed to the expanded use of newer generation drug-eluting stents that generally require less duration of DAPT compared to their older counterparts. While the overall analysis favored the 1-month DAPT strategy, the investigators nonetheless also acknowledged the need for additional studies to further explore the optimal duration of DAPT in the post-ACS setting.