Early aspirin discontinuation and transition to a P2Y12 inhibitor monotherapy may lower bleeding risk in those at low ischaemic risk after myocardial infarction (MI), a randomised trial has found.
The findings of the TARGET-FIRST trial were presented at the European Society of Cardiology (ESC) Congress 2025 and simultaneously published in the New England Journal of Medicine.
Current ESC Guidelines recommend 12 months of dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor after percutaneous coronary intervention as standard therapy in patients with acute MI.
The TARGET-FIRST trial considered the impact of early aspirin discontinuation and compared 11 months of P2Y12 inhibitor monotherapy with continued DAPT in acute MI patients who had achieved early complete revascularisation by stenting and completed one month of uneventful DAPT.
P2Y12 inhibitor monotherapy benefits
The researchers found P2Y12 inhibitor monotherapy was noninferior to dual antiplatelet therapy for cardiovascular and cerebrovascular outcomes, and was superior in reducing clinically relevant bleeding, supporting de-escalation in carefully selected low-risk patients.
‘No randomised trials have previously assessed early aspirin discontinuation in acute MI patients who achieve early, complete revascularisation with modern stents,’ explained principal investigator, Professor Giuseppe Tarantini, head of the Interventional Cardiology Unit within the Department of Cardiac, Thoracic and Vascular Sciences at the University of Padua Medical School in Padua, Italy.
‘In such cases, bleeding risk may outweigh residual ischaemic risk, making antiplatelet therapy de-escalation attractive,’ he said.
The open-label randomised controlled trial was conducted at 40 European centres. Eligible adults with an ST-segment elevation MI (STEMI) or non-STEMI underwent complete revascularisation within seven days using a contemporary drug-eluting stent, and completed one month of DAPT without adverse events.
Among the 2,246 patients who enrolled for the trial, 1,942 underwent 1:1 randomisation. A total of 981 continued dual antiplatelet therapy and 961 received a P2Y12 inhibitor as monotherapy for 11 months. The mean age of the participants was 61 years and 21.6% were women.
The primary endpoint was a composite of all-cause death, myocardial infarction, stent thrombosis, stroke or major bleeding, which was defined by the Bleeding Academic Research Consortium (BARC) as a bleeding event of type 3 or 5 bleeding, at 11 months following randomisation. Noninferiority was defined as an absolute difference of 1.25 percentage points in the upper bound of the two-sided 95% confidence interval (CI).
Optimal medical therapy
A primary endpoint event occurred in 2.10% of patients (n=20) in the P2Y12 inhibitor monotherapy group and 2.18% of patients (n=21) in the DAPT group (difference, -0.09 percentage points; 95% CI – 1.39 to 1.20; p=0.021 for noninferiority).
MI occurred in 0.7% versus 1.1%, definite/probable stent thrombosis in 0.1% versus 0.0%, and ischaemic stroke in 0.3% versus 0.2%, respectively. BARC-type 3 or 5 bleeding occurred in 0.7% in each group.
Stent thrombosis was infrequent, the trial authors noted, and the incidence was similar in the two groups. The incidence of serious adverse events also appeared to be similar in the two groups, they added.
The main secondary endpoint was BARC-type 2, 3 or 5 bleeding (clinically relevant bleeding). This occurred in 2.6% of patients in the P2Y12 inhibitor monotherapy group, and 5.6% of those in the dual antiplatelet therapy group (hazard ratio [HR] 0.46; 95% CI 0.29 to 0.75; p=0.002 for superiority).
Patient-oriented composite outcomes, including all-cause death, MI, stent thrombosis, stroke, repeat ischaemia-driven revascularisation or BARC-type 2, 3 or 5 bleeding, occurred in 4.5% in the monotherapy group and 7.2% in the DAPT group (HR 0.61; 95% CI 0.42 to 0.89).
Therapy adherence at 11 months was high in both groups, with 86.9% on monotherapy and 88.6% on DAPT).
Professor Tarantini said: ‘In low-risk acute myocardial infarction patients with early complete revascularisation and no complications after one month of DAPT, switching to P2Y12 inhibitor monotherapy maintained protection from ischaemic events and reduced bleeding.
‘These results reflect the benefits of modern stents, high procedural success and optimal medical therapy, making early aspirin discontinuation feasible in this selected population.’
