Two major clinical trials presented at ESC Congress 2025 are challenging the current standard of 12 months of dual antiplatelet therapy (DAPT) following myocardial infarction, with both studies suggesting that shorter treatment durations may offer comparable efficacy with improved safety profiles.
DUAL-ACS Trial: Three Months May Be Sufficient
The DUAL-ACS trial, an open-label, investigator-initiated randomized study, compared 3 months versus 12 months of DAPT in a real-world population of 5,052 patients with myocardial infarction. Led by Professor David Newby from the University of Edinburgh, the study recruited patients from Scotland, England, and New Zealand who had experienced a type 1 MI within 12 weeks.
"In patients after a heart attack, the first 1–3 months is associated with the highest risk of recurrent events. Evidence indicates that compared to the guideline recommendations of 12 months of DAPT, shorter DAPT durations have equivalent efficacy in reducing recurrent events, with a lower risk of major bleeding and a trend towards lower death rates in MI patients treated with stents," explained Professor Newby.
The trial population had a mean age of 63 years with 27% female participants. Following the index admission, 23% received medical management only, 70% underwent percutaneous coronary intervention, and 6% had coronary artery bypass graft surgery.
After 15 months of follow-up, the primary endpoint of all-cause mortality occurred in 2.7% of patients in the 3-month DAPT group compared to 3.4% in the 12-month group (hazard ratio 0.78; 95% confidence interval 0.57 to 1.07; p=0.1232). There was no difference in cardiovascular death or non-fatal MI between groups (HR 1.04; 95% CI 0.87 to 1.26; p=0.6149).
Importantly, fatal and non-fatal major bleeding occurred in 3.2% of patients receiving 3 months of DAPT versus 4.0% in the 12-month group (HR 0.78; 95% CI 0.58 to 1.06; p=0.0977).
TARGET-FIRST Trial: Early Aspirin Discontinuation Strategy
The TARGET-FIRST trial took a different approach, examining early transition to P2Y12 inhibitor monotherapy in carefully selected low-risk patients. This open-label randomized controlled trial, conducted at 40 European centers and led by Professor Giuseppe Tarantini from the University of Padua, enrolled 1,942 patients with acute MI who achieved early complete revascularization and completed one month of uneventful DAPT.
"No randomised trials have previously assessed early aspirin discontinuation in acute MI patients who achieve early, complete revascularisation with modern stents. In such cases, bleeding risk may outweigh residual ischaemic risk, making antiplatelet therapy de-escalation attractive," Professor Tarantini explained.
Patients were randomized 1:1 to continue DAPT or switch to P2Y12 inhibitor monotherapy for 11 months. The study population had a mean age of 61 years with 21.6% women.
The primary composite endpoint of all-cause death, MI, stent thrombosis, stroke, or major bleeding occurred in 2.10% of the monotherapy group versus 2.18% of the continued DAPT group (difference −0.09 percentage points; 95% CI −1.39 to 1.20; p=0.021 for noninferiority), meeting the noninferiority threshold.
Significant Bleeding Reduction with Monotherapy
The most striking finding from TARGET-FIRST was the significant reduction in clinically relevant bleeding. The main secondary endpoint of BARC type 2/3/5 bleeding was significantly lower with P2Y12 inhibitor monotherapy (2.65% vs. 5.57%; hazard ratio 0.46; 95% CI 0.29 to 0.75; p=0.002).
The patient-oriented composite outcome, which included all-cause death, MI, stent thrombosis, stroke, repeat ischemia-driven revascularization, or clinically relevant bleeding, occurred in 4.5% of the monotherapy group compared to 7.2% in the DAPT group (HR 0.61; 95% CI 0.42 to 0.89). Therapy adherence remained high in both groups at 11 months (86.9% with monotherapy and 88.6% with DAPT).
Clinical Implications and Future Guidelines
Both trials suggest that current ESC Guidelines recommending 12 months of DAPT after percutaneous coronary intervention for MI may need revision. The DUAL-ACS investigators noted that while their study recruited only 30% of planned participants and couldn't definitively address the primary question, "there was no evidence that DAPT given for 12 months conferred any additional benefit."
Professor Newby concluded that "the trends for lower mortality and bleeding risk with 3 months of DAPT are consistent with prior meta-analyses and suggest that limiting DAPT duration to 3 months may be safer in a real-world contemporary population."
Similarly, Professor Tarantini emphasized that the TARGET-FIRST results "reflect the benefits of modern stents, high procedural success and optimal medical therapy, making early aspirin discontinuation feasible in this selected population."
Both studies were simultaneously published in major medical journals, with TARGET-FIRST appearing in the New England Journal of Medicine, underscoring their potential impact on clinical practice and future guideline development.
