Abbreviated Dual Antiplatelet Therapy with Prasugrel: 4D-ACS

The optimal duration of dual antiplatelet therapy (DAPT) in acute coronary syndrome (ACS) remains subject to controversy. While current guidelines recommend 12 months of DAPT with aspirin and a strong P2Y12 inhibitor, concerns about bleeding risk have driven shortening and de-escalation strategies, especially in populations at high bleeding risk.

In this context, Youngwoo Jang et al. conducted the 4D-ACS study, an open-label, randomized clinical trial that evaluated 1-month DAPT with standard-dose prasugrel, followed by prasugrel 5 mg monotherapy, compared to conventional 12-month DAPT using reduced-dose prasugrel.

The study included 656 patients with ACS (ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, and unstable angina) who underwent percutaneous coronary intervention (PCI) with BioFreedom Ultra stents (Biosensors). Participants were randomized to two strategies: 1-month DAPT followed by reduced-dose prasugrel (1M-DAPT) versus conventional 12-month DAPT (12M-DAPT).

The primary endpoint (PFP) was the 12-month incidence of net adverse clinical events (NACE), defined as a composite of all-cause mortality, non-fatal myocardial infarction, ischemia-driven revascularization, stroke, and major bleeding (BARC type 3 or 5).

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In the intention-to-treat analysis, the incidence of NACE was significantly lower in the 1M-DAPT group (4.9% vs. 8.8%; hazard ratio [HR] 0.51; p = 0.034), driven primarily by a 77-% reduction in major bleeding (BARC 3–5) (0.6% vs. 4.6%; HR 0.13; p = 0.007), without compromising ischemic safety (no differences in MI, revascularization, stroke, or stent thrombosis).

In subgroups of patients with very high bleeding risk, the benefit was even more pronounced, with a lower incidence of NACE (HR 0.44; 95% confidence interval [CI]: 0.21–0.89).

These findings add to the growing body of evidence supporting DAPT shortening in ACS and suggest that combining ultra-short duration with pharmacological de-escalation may optimize the balance between ischemic and bleeding risks, especially in populations more susceptible to bleeding, such as Asians.

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Regarding clinical practice, this strategy emerges as a viable alternative for ACS patients at high bleeding risk undergoing PCI with next-generation stents, aligning with the trend toward shorter and more personalized therapies.

Conclusions

An ultra-short 1-month DAPT strategy with de-escalation to reduced-dose prasugrel in ACS patients significantly reduced net clinical events, primarily due to lower bleeding incidence, without increasing the risk of ischemic events. This approach appears safe and effective, particularly in Asian patients at high bleeding risk.

Original Title: One-month dual antiplatelet therapy followed by Prasugrel monotherapy at a reduced dose: the 4D-ACS randomised trial.

Referenec: Jang Y, Park SD, Lee JP, Choi SH, Kong MG, Won YS, Kim M, Lee KH, Han SH, Kwon SW, Suh J, Kang WC. One-month dual antiplatelet therapy followed by prasugrel monotherapy at a reduced dose: the 4D-ACS randomised trial. EuroIntervention. 2025 Jul 21;21(14):e796-e809. doi: 10.4244/EIJ-D-25-00331. PMID: 40392195; PMCID: PMC12285397.