Key Points:
- This trial randomized 6,000 patients with high bleeding risk or acute coronary syndrome undergoing planned PCI to a strategy of 3.75mg of prasugrel or DAPT with aspirin 81-100 mg and prasugrel 3.75mg, following a prasugrel load in both arms.
- At 1 month, prasugrel alone failed to demonstrate superiority for the co-primary endpoint of major bleeding. However, the aspirin-free strategy was non-inferior to DAPT for the co-primary endpoint of cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke).
- DAPT remains the standard strategy post-PCI even in the current era with the newest generation of drug-eluting stents.
Optimal Antiplatelet Strategy for ACS Patients with High Bleeding Risk: Examining the Pendulum Shift
For over a decade, the focus after percutaneous coronary interventions (PCI) has centered on reducing the risk of thrombosis. However, in recent times, there has been a significant shift towards mitigating bleeding risk in patients with acute coronary syndrome (ACS) and high bleeding risk (HBR). Trials have continually pushed the boundaries to determine the optimal duration of dual antiplatelet therapy (DAPT) for these patients post-PCI. The debate over the safety and effectiveness of an aspirin-free strategy following PCI has been intense. Researchers from the Kyoto University, Graduate School of Medicine, have remained at the forefront of such trials.
In a hotline session at the ESC Congress 2023 on August 26th, Dr. Masahiro Natsuaki of Saga University, Japan, presented findings from the STOPDAPT-3 trial. This trial compared prasugrel monotherapy to DAPT – aspirin and prasugrel, followed by aspirin monotherapy after 1 month post-PCI among HBR or ACS patients planned for PCI with the newest cobalt-chromium everolimus-eluting stents.
The trial enrolled 6,002 patients from 72 centers in Japan, randomly assigning them in a 1:1 fashion to prasugrel monotherapy (3.75 mg/day) or DAPT with aspirin (81-100 mg/day) and prasugrel, following a loading dose of prasugrel 20 mg in both groups. The mean age was 71.6 years, with 23.4% being women.
There was no difference between the groups for the co-primary bleeding endpoint of major bleeding events (defined as Bleeding Academic Research Consortium [BARC] type 3 or 5) at 1 month (4.47% vs. 4.71%; hazard ratio [HR], 0.95; 95% CI, 0.75-1.20, p=0.66). However, the prasugrel monotherapy group was non-inferior to DAPT for the co-primary cardiovascular endpoint (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) at 1 month (4.12% vs. 3.69%; HR, 1.12; 95% CI, 0.87-1.45; p for non-inferiority=0.01). Notably, the net clinical benefit, a composite of the primary co-primary bleeding and cardiovascular endpoints, was similar in both groups (7.14% vs. 7.38%). Likewise, the incidence of all-cause death was also comparable (2.28% vs. 2.11%).
While definite stent thrombosis didn’t differ between the two groups, there was a higher incidence of any coronary revascularization (1.15% vs. 0.57%) and definite or probable stent thrombosis (0.71% vs. 0.44%) in the aspirin-free group.
Dr. Masahiro Natsuaki concluded: “The aspirin-free strategy compared with the DAPT strategy failed to reduce major bleeding within 1 month after PCI, but it was non-inferior for the co-primary cardiovascular endpoint with a relative 50% margin. Aspirin used for a limited period of 1 month after PCI as part of DAPT might have provided protective effects on vulnerable coronary lesions, particularly in ACS patients, without significantly increasing major bleeding. DAPT should remain the standard strategy for PCI, even in the era of new-generation drug-eluting stents.”
