OPTIMA-AF
(2026)Objective
To compare the efficacy and safety of 1-month versus 12-month dual antithrombotic therapy (DOAC plus P2Y12 inhibitor) followed by DOAC monotherapy after percutaneous coronary intervention in patients with atrial fibrillation.
Study Summary
• 1-month therapy was superior for the primary safety endpoint of major or clinically relevant non-major bleeding (4.5% vs 8.8%; absolute difference −4.4 percentage points [95% CI −7.3 to −1.4]; HR 0.50 [95% CI 0.30–0.81]; p=0.0041)
• Overall net clinical profile favored the 1-month strategy, though efficacy findings warrant caution given lower-than-anticipated event rates and a fixed absolute non-inferiority margin
Intervention
1-month DOAC plus P2Y12 inhibitor (clopidogrel 75 mg or prasugrel 3.75 mg daily) followed by DOAC monotherapy, versus 12-month DOAC plus P2Y12 inhibitor followed by DOAC monotherapy, after PCI with intravascular imaging guidance using an everolimus-eluting stent
Inclusion Criteria
Age ≥20 years with non-valvular atrial fibrillation, CHADS2 score ≥1, undergoing PCI for native coronary lesions for chronic coronary syndrome or unstable angina, with planned post-PCI DOAC treatment
Study Design
Arms: 1-month dual antithrombotic therapy (DOAC + P2Y12 inhibitor) then DOAC monotherapy (n=542) vs 12-month dual antithrombotic therapy then DOAC monotherapy (n=537)
Patients per Arm: 542 vs 537
Outcome
• Primary safety (ISTH major or clinically relevant non-major bleeding at 12 months): 24 vs 47 patients (4.5% vs 8.8%; difference −4.4 pp [95% CI −7.3 to −1.4]; HR 0.50 [0.30–0.81]; p=0.0041 for superiority)
• Superiority for efficacy was not demonstrated
Bottom Line
In patients with atrial fibrillation and predominantly chronic coronary syndrome undergoing imaging-guided PCI, 1-month dual antithrombotic therapy (DOAC plus P2Y12 inhibitor) followed by DOAC monotherapy was non-inferior to 12-month dual therapy for death or thromboembolic events and halved major or clinically relevant non-major bleeding, supporting earlier de-escalation to DOAC monotherapy — though efficacy findings warrant caution given lower-than-anticipated event rates and a fixed absolute non-inferiority margin.
Major Points
- 1-month dual antithrombotic therapy was non-inferior to 12-month therapy for the primary efficacy endpoint of all-cause death or thromboembolic events at 12 months (5.4% vs 4.3%; absolute difference 1.1 pp [95% CI −1.5 to 3.6], upper limit below the 5.0 pp non-inferiority margin; HR 1.25 [95% CI 0.73–2.17])
- 1-month dual therapy was superior for the primary safety endpoint of ISTH major or clinically relevant non-major bleeding at 12 months (4.5% vs 8.8%; absolute difference −4.4 pp [95% CI −7.3 to −1.4]; HR 0.50 [95% CI 0.30–0.81]; p=0.0041)
- Fixed-sequence hierarchical testing: non-inferiority for efficacy met, superiority for safety met; superiority for efficacy was not demonstrated
- All PCI was performed with intravascular imaging guidance (OCT or IVUS) using the Xience everolimus-eluting stent, limiting generalizability to non-imaging-guided PCI
- Population was predominantly chronic coronary syndrome (acute coronary syndrome limited to unstable angina; STEMI and NSTEMI excluded); applicability to ACS populations requires further trials
- Event rates were lower than anticipated (assumed 10% control efficacy event rate vs observed 4.3%), so the fixed 5.0 pp non-inferiority margin warrants cautious interpretation of efficacy results
Study Design
- Study Type
- Prospective, investigator-initiated, multicentre, open-label, blinded-endpoint, active-control, randomised, hybrid non-inferiority and superiority trial
- Randomization
- Yes
- Blinding
- Open-label (patients and physicians unmasked); clinical events adjudicated by an independent committee masked to treatment allocation
- Sample Size
- 1088
- Follow-up
- Median 540 days (IQR 517–559); primary assessment at 12 months (censored at day 360); visits at 1, 12, and 18 months
- Centers
- 75
- Countries
- Japan
Primary Outcome
Definition: Composite of all-cause death or thromboembolic events (myocardial infarction, definite stent thrombosis, stroke, or systemic embolism)
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 23 patients (Kaplan–Meier estimate 4.3%) in 12-month dual therapy group | 29 patients (Kaplan–Meier estimate 5.4%) in 1-month dual therapy group | 1.25 (0.73–2.17) |
Limitations & Criticisms
- Event rates were lower than anticipated (observed ~4–5% vs assumed 10%), making the fixed 5.0 percentage point absolute non-inferiority margin generous relative to observed risk; efficacy findings require cautious interpretation
- Open-label design (patients and treating physicians unmasked), although endpoint adjudication was blinded
- Population restricted to Japan and likely predominantly east Asian; generalizability to other populations uncertain
- STEMI and NSTEMI excluded (ACS limited to unstable angina), limiting applicability to acute coronary syndrome populations
- All PCI required intravascular imaging guidance and a single stent platform (Xience everolimus-eluting stent), which may limit generalizability to routine practice
- Point estimate for efficacy numerically favored the 12-month group (HR 1.25) with a wide confidence interval (0.73–2.17)
Citation
Sotomi Y, Kozuma K, Higuchi Y, et al. 1-month versus 12-month dual antithrombotic therapy after percutaneous coronary intervention in patients with atrial fibrillation (OPTIMA-AF): a multicentre, open-label, hybrid non-inferiority and superiority, randomised, controlled trial. Lancet. Published online July 15, 2026. doi:10.1016/S0140-6736(26)00665-3