P2Y12 inhibitor monotherapy was noninferior to 1 month of dual antiplatelet therapy (DAPT) in low-risk patients with acute myocardial infarction (AMI), according to new data from the TARGET FIRST trial. Giuseppe Tarantini, MD, PhD, from the University of Padova, Italy, presented these findings during a Hot Line session on Sunday at the European Society of Cardiology (ESC) Congress 2025 in Madrid. To date, no randomized controlled trials have examined the potential differences between complete revascularization and duration of DAPT in low-risk patients with AMI. The TARGET FIRST trial, an open-label randomized study, took place across 40 sites in the European Union, and the investigators examined alternatives to 12-month DAPT treatment in patients with AMI. A composite of all-cause death, MI, stent thrombosis, stroke or Bleeding Academic Research Consortium (BARC) type 3/5 bleeding at 11-months was the primary endpoint for TARGET FIRST. Patients were randomized 1:1 to continue with DAPT for 11 months after the initial first month of DAPT, or switch to P2Y12 inhibitor monotherapy for the remainder of the time. A total of 1,942 patients were randomized (mean age=61 years, 21.6% women). In the P2Y12 monotherapy group, the primary endpoint occurred in 2.10% of patients, and 2.18% of patients in the continued DAPT group experienced the primary endpoint (hazard ratio [HR]=0.46, 95% confidence interval [CI]: -1.39 to 1.20, p for noninferiority=0.021). Rates of MI and stent thrombosis were comparable between the two groups. Adherence to therapy at 11-months was also similar and high (P2Y12 group=86.9%, DAPT group=88.6%). The main secondary endpoint, however, was significantly lower in the P2Y12 group (BARC type 2/3/5 bleeding; P2Y12 group=2.65% versus DAPT group=5.57%; HR=0.46; 95% CI=0.29-0.75; p=0.002). Overall, low-risk patients who switched to P2Y12 inhibitor monotherapy after undergoing early complete revascularization plus one month of DAPT saw the same benefits, and less bleeding, than patients who underwent 12 months of standard DAPT treatment. Image Credit: European Society of Cardiology (ESC) Congress 2025 Press Office