STOPDAPT-3 Trial in Japan Compares Monotherapy and DAPT After PCI With Stenting

August 26, 2023—Late-breaking research presented in a Hot Line session at the European Society of Cardiology (ESC) Congress 2023 showed that prasugrel monotherapy after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) is not superior to dual antiplatelet therapy (DAPT) for major bleeding but is noninferior for cardiovascular events in patients with acute coronary syndrome (ACS) or high bleeding risk (HBR).

According to the ESC press release, the findings were from the STOPDAPT-3 trial that investigated the efficacy and safety of aspirin-free prasugrel monotherapy compared with 1-month DAPT with aspirin and prasugrel in patients with ACS or HBR undergoing PCI with cobalt-chromium everolimus-eluting stents.

STOPDAPT-3 study investigator Masahiro Natsuaki, MD, of Saga University in Saga, Japan, presented the findings at the ESC Congress, which was held August 25-28 in Amsterdam, the Netherlands.

According to the ESC press release, the study enrolled 6,002 patients with ACS or HBR from 72 centers in Japan from January 2021 and April 2023. Just before PCI, patients were randomized (1:1) to prasugrel (3.75 mg/day) monotherapy or to DAPT with aspirin (81-100 mg/day) and prasugrel after a loading dose of prasugrel (20 mg) in both groups.

There were two primary endpoints:

1. Major bleeding events (defined as Bleeding Academic Research Consortium type 3 or 5) at 1 month for superiority
2. Cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) at 1 month for noninferiority

The major secondary endpoint was a composite of the coprimary bleeding and cardiovascular endpoints (cardiovascular death, myocardial infarction, definite stent thrombosis, stroke, or major bleeding) at 1 month representing the net clinical benefit.

The ESC press release advised that the population of the full analysis set was composed of 5,966 patients (no-aspirin group: 2,984 patients; DAPT group: 2,982 patients). The average age of patients was 71.6 years, and 23.4% were women.

Dr. Natsuaki reported the following, as noted in the press release:

• At 1 month, the no-aspirin strategy was not superior to DAPT for the coprimary bleeding endpoint (4.47% vs 4.71%; hazard ratio [HR], 0.95; 95% CI, 0.75-1.20; P for superiority = .66).
• The no-aspirin strategy was noninferior to DAPT with a relative 50% margin for the coprimary cardiovascular endpoint (4.12% vs 3.69%; HR, 1.12; 95% CI, 0.87-1.45; P for noninferiority = .01).
• There was no between-group difference in the incidence of all-cause death (no-aspirin group, 2.28% vs DAPT group, 2.11%).
• The major secondary endpoint occurred in 7.14% of patients in the no-aspirin group and 7.38% of patients in the DAPT group, with no between-group difference, indicating a similar effect on net clinical benefit for both groups.
• There was an excess of any coronary revascularization (1.15% vs 0.57%) and definite or probable stent thrombosis (0.71% vs 0.44%) in the no-aspirin group compared with the DAPT group.
• Definite stent thrombosis was not different between the two groups (0.47% vs. 0.37%).
• In a subgroup analysis stratified by ACS and non-ACS, the excess risk of cardiovascular events in the no-aspirin group compared with the DAPT group was seen in patients with ACS but not in those without ACS.

“The aspirin-free strategy compared with the DAPT strategy failed to reduce major bleeding within 1 month after PCI, but it was noninferior for the coprimary cardiovascular endpoint with a relative 50% margin,” commented Dr. Natsuaki in the ESC press release.

Dr. Natsuaki continued, “Aspirin used for a limited period of 1 month after PCI as a component of DAPT might have exerted a protective effect on vulnerable coronary lesions, particularly in patients with ACS, without a large increase in major bleeding. DAPT should remain the standard strategy for PCI even in the new-generation DES era.”

ESC guidelines recommend 6 months of DAPT in HBR patients with ACS and 12 months of DAPT in non-HBR patients with ACS after PCI. In patients with non-ACS, 1 to 3 months of DAPT is recommended in HBR patients after PCI, noted the ESC press release.