A one-month course of dual antiplatelet therapy (DAPT) followed by reduced-dose prasugrel monotherapy significantly reduced bleeding events without increasing ischaemic risk compared to standard 12-month DAPT in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), according to the 4D-ACS randomised trial, presented at EuroPCR 2025 in Paris, France.
The management of patients with ACS after PCI has traditionally relied on prolonged DAPT to minimise the risk of stent thrombosis and other ischaemic complications, but this comes at the cost of increased bleeding, which can be life-threatening and negatively impact long-term outcomes. There has been growing interest in tailoring antiplatelet regimens to individual patient risk, particularly by shortening DAPT duration or reducing drug intensity. The 4D-ACS trial was designed to test whether a de-escalation strategy – one month of DAPT with aspirin and prasugrel, followed by prasugrel 5 mg monotherapy – could offer similar ischaemic protection with fewer bleeding complications compared to the conventional 12-month DAPT protocol.
In this multicentre, double-blind trial, 656 East Asian patients with ACS were randomised immediately post-PCI with a biolimus-coated drug-eluting stent to either the 1M-DAPT group (one month DAPT then prasugrel 5 mg monotherapy) or the 12M-DAPT group (twelve months DAPT with aspirin and prasugrel 5 mg). The primary endpoint was net adverse clinical events (NACE) at 12 months, a composite of death, non-fatal myocardial infarction, stroke, ischaemia-driven target vessel revascularisation, and BARC type 2-5 bleeding. Results showed NACE occurred in 4.9% of the 1M-DAPT group versus 8.8% in the 12M-DAPT group, demonstrating both non-inferiority and superiority. Major bleeding was significantly reduced in the 1M-DAPT group (0.6% vs 4.6%, HR 0.13; p=0.007), while ischaemic outcomes remained similar between groups.
These findings support a shift towards more individualised antiplatelet therapy, particularly for patients at high risk of bleeding. For clinical practice, a one-month DAPT regimen followed by low-dose prasugrel monotherapy may offer enhanced safety without compromising ischaemic protection, especially in selected populations. However, further studies are needed in more diverse patient groups and with different stent types before widespread adoption. Clinicians should consider patient-specific bleeding and ischaemic risks when choosing antiplatelet strategies, moving towards a more dynamic, risk-adapted approach in ACS management.
Reference
Kang WC et al. One-month DAPT followed by dose reduction of prasugrel after drug-coated stent insertion in Acute Coronary Syndrome. EuroPCR 2025, 20-23 May, 2025.
