Escalated Single Platelet Inhibition for One Month Plus Direct Oral Anticoagulation in Patients With Atrial Fibrillation and acUte coRonary Syndrome Undergoing percutaneoUS Coronary Intervention (EPIDAURUS)

doi:10.1038/s41591-026-04629-7

EPIDAURUS

Patient / Population Intervention / Exposure Comparison Outcome

In 602 patients with atrial fibrillation and ACS after PCI, one month of a potent P2Y12 inhibitor plus a NOAC did not reduce major ischaemic events at 6 weeks compared with clopidogrel plus a NOAC.

N

602patients

Design

Investigator-initiated, multicentre, randomised, open-label trial with blinded outcome assessment (sponsor LMU Munich); 1:1 randomisation within 24 hours of successful PCI; co-primary endpoints at 6 weeks tested for superiority (ischaemic composite) and non-inferiority (death or bleeding)

Endpoint

Co-primary at 6 weeks — (1) major ischaemic events, the composite of all-cause death, myocardial infarction, definite or probable stent thrombosis, ischaemic stroke, systemic thromboembolism or urgent revascularisation (superiority); (2) death or BARC type 2 or higher bleeding (non-inferiority)

Relevance

3Supporting — context rather than must-know.

ResultStopped early after 602 of a planned 1,474 patients. BARC type 3 or higher bleeding more than tripled with the potent P2Y12 inhibitor (HR 3.54, 95% CI 1.15-10.85; P = 0.028). No difference in cardiovascular death, myocardial infarction or stroke at 6 weeks or 6 months.

Rizas KD, et al. Presented at ESC Congress 2026, Hot Line 3, 29 August; simultaneously published in Nat Med. 10.1038/s41591-026-04629-7

Discussion & critique

A question asked and answered in the direction nobody wanted: adding prasugrel or ticagrelor rather than clopidogrel to a NOAC after infarction tripled major bleeding and bought nothing ischaemic. The trial stopped at 602 of 1,474 patients, so the ischaemic comparison is underpowered and the bleeding interval is wide — 1.15 to 10.85 — but the direction is unambiguous and the harm is the one that shows up first. Read as a boundary on the potent P2Y12 inhibitors in anticoagulated patients, not as a precise estimate.