The Lancet August 01, 2026

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

Yohei Sotomi, Ken Kozuma, Yoshiharu Higuchi, Gaku Nakazawa, et al.

Bottom Line

In patients with atrial fibrillation undergoing percutaneous coronary intervention, one month of dual antithrombotic therapy followed by DOAC monotherapy was non-inferior to 12 months of dual therapy for ischemic events and superior for reducing bleeding.

Key Findings

1. The primary efficacy endpoint (composite of all-cause death or thromboembolic events) occurred in 5.4% of patients in the 1-month group versus 4.3% in the 12-month group (HR 1.25; absolute difference 1.1 percentage points; P=0.002 for non-inferiority).

2. The primary safety endpoint (major or clinically relevant non-major bleeding) occurred in 4.5% of the 1-month group versus 8.8% in the 12-month group (HR 0.50; absolute difference -4.4 percentage points; P=0.0041 for superiority).

3. All-cause mortality was numerically higher in the 1-month arm (4.1% vs. 2.8%), primarily driven by non-cardiovascular deaths.

4. The reduction in bleeding was predominantly driven by clinically relevant non-major bleeding (HR 0.26), while the incidence of major bleeding was statistically similar between the two groups (HR 0.77).

Study Design

Design

RCT

Open-Label

Sample

1,079

Patients

Duration

12 mo

Median

Setting

Multicenter, Japan

Population Patients with non-valvular atrial fibrillation undergoing percutaneous coronary intervention (94% with chronic coronary syndrome)

Intervention 1 month of dual antithrombotic therapy (DOAC plus a P2Y12 inhibitor) followed by DOAC monotherapy

Comparator 12 months of dual antithrombotic therapy (DOAC plus a P2Y12 inhibitor)

Outcome Coprimary endpoints of efficacy (composite of all-cause death or thromboembolic events for non-inferiority) and safety (ISTH major or clinically relevant non-major bleeding for superiority) at 12 months

Study Limitations

• The observed event rates were significantly lower than initially anticipated, making the fixed non-inferiority margin of 5% relatively wide, which necessitates cautious interpretation of the efficacy estimates.

• The trial enrolled a population comprising 94% chronic coronary syndrome patients, limiting its generalizability to patients presenting with acute coronary syndromes (ACS).

• The study was conducted exclusively in Japanese patients, which may limit extrapolation to more diverse global populations with different baseline bleeding and ischemic risk profiles.

• The open-label design carries an inherent risk of bias in the ascertainment and adjudication of softer clinical endpoints.

Clinical Significance

The OPTIMA-AF trial provides critical evidence supporting a 'less is more' approach for patients with atrial fibrillation undergoing PCI. By shortening dual antithrombotic therapy to just one month, clinicians can significantly reduce bleeding risks—specifically clinically relevant non-major bleeding—without an unacceptable increase in thromboembolic events compared to the traditional 12-month regimen, especially in stable patients.

Historical Context

The management of patients with atrial fibrillation who require PCI has historically been a clinical dilemma, balancing the high bleeding risk of triple therapy (oral anticoagulation plus dual antiplatelet therapy) against the risk of stent thrombosis and stroke. Landmark trials such as PIONEER AF-PCI, RE-DUAL PCI, AUGUSTUS, and ENTRUST-AF PCI established that dropping aspirin early (dual therapy with a DOAC and a P2Y12 inhibitor) was safer than prolonged triple therapy. OPTIMA-AF advances this paradigm by addressing the optimal duration of the dual therapy phase, showing that further de-escalation to DOAC monotherapy after only 1 month may be safe and effective.

Guided Discussion

High-yield insights from every perspective

Med Student

Medical Student

Why do patients with both atrial fibrillation and a recent coronary stent require two different types of antithrombotic medications initially, and what distinct pathophysiological pathways do these drugs target?

Key Response

Atrial fibrillation primarily causes stasis-related fibrin-rich 'red' clots, which are best targeted by oral anticoagulants (DOACs) inhibiting factor Xa or IIa. In contrast, coronary stents provoke platelet-rich 'white' clots, requiring antiplatelet agents like P2Y12 inhibitors. This dual mechanism explains the historical need for combined therapy, balancing systemic embolic protection with the prevention of local stent thrombosis.

Resident

A 72-year-old patient with persistent AF undergoes PCI with a drug-eluting stent. Based on the OPTIMA-AF trial, how might you adjust their antithrombotic regimen at the 1-month follow-up, and what clinical factors must you assess before making this change?

Key Response

Traditional management often continued dual antithrombotic therapy (DOAC plus a P2Y12 inhibitor) for 6 to 12 months. OPTIMA-AF suggests transitioning to DOAC monotherapy at 1 month is safe for ischemic outcomes and reduces bleeding. However, residents must actively weigh bleeding scores (e.g., HAS-BLED) against high ischemic risk factors (e.g., complex PCI, bifurcation stenting, or prior stent thrombosis) before routinely discontinuing the antiplatelet agent.

Fellow

The OPTIMA-AF trial demonstrated non-inferiority for ischemic events when dropping the antiplatelet agent at 1 month. How does coronary anatomical complexity impact your willingness to apply these results, and what pathophysiological risks persist beyond 1 month in these specific subsets?

Key Response

High-risk PCI subsets (e.g., left main disease, complex bifurcations, total stent length greater than 60mm) are often underrepresented in broad AF-PCI trials. Complete endothelialization of complex drug-eluting stents can take considerably longer than 1 month, maintaining a higher risk of late stent thrombosis. Fellows must critically evaluate whether the non-inferiority margin observed in the general trial population safely extends to these complex anatomical subsets.

Attending

With the shift towards very short (1-month) dual antithrombotic therapy in AF-PCI patients, how do we reconcile the standard requirement of 6-12 months of DAPT in non-AF patients with the apparent safety of DOAC monotherapy at 1 month in the OPTIMA-AF population?

Key Response

This highlights a major clinical paradox. If DOAC monotherapy sufficiently prevents stent thrombosis at 1 month in AF patients, it suggests either that DOACs possess adequate collateral antiplatelet-like effects, or that we are consciously accepting a marginally higher, yet statistically non-inferior, ischemic risk to avoid a devastating bleeding risk. Attendings must navigate and teach this complex risk-benefit calculus when discussing the evolution of antithrombotic paradigms.

Scholarly Review

Critical appraisal through the lens of expert reviewers and guideline development

PhD

OPTIMA-AF utilizes a hybrid non-inferiority (for ischemia) and superiority (for bleeding) design in an open-label setting. How does the open-label nature introduce potential ascertainment bias, and why is the distinction between intention-to-treat and per-protocol analyses critical for the non-inferiority endpoint?

Key Response

Open-label designs can lead to biased reporting of subjective endpoints like minor bleeding, heavily influencing the superiority outcome. For the non-inferiority ischemic endpoint, a standard intention-to-treat analysis can inherently bias the results towards the null (non-inferiority) due to crossovers or non-adherence. Therefore, a robust per-protocol analysis is statistically essential to ensure the non-inferiority margin wasn't met simply due to diluted intervention effects.

Journal Editor

As an editor evaluating the OPTIMA-AF manuscript, what specific concerns would you raise regarding the justification of the prespecified non-inferiority margin for ischemic events, and how might the inclusion of newer ultra-thin strut stents confound the historical event rates used for power calculations?

Key Response

A critical reviewer will heavily scrutinize the non-inferiority margin; if set too wide, an unacceptable absolute increase in myocardial infarction or stent thrombosis could be mathematically deemed 'non-inferior'. Additionally, modern ultra-thin strut stents inherently lower stent thrombosis rates compared to older platforms. Using older historical data to power the trial might inflate expected event rates, artificially making the 1-month experimental strategy appear safer than it is.

Guideline Committee

Current ACC/AHA and ESC guidelines generally recommend 6 months of dual antithrombotic therapy for AF patients post-uncomplicated PCI. Based on the OPTIMA-AF findings, how should these algorithms be revised, and what specific Class of Recommendation (COR) and Level of Evidence (LOE) would you assign to DOAC monotherapy at 1 month?

Key Response

Recent guidelines (e.g., 2020 ESC AF and 2021 ACC/AHA Revascularization) recommend early cessation of aspirin but typically continue a P2Y12 inhibitor alongside a DOAC for 6 months. OPTIMA-AF provides LOE B-R or A (depending on meta-analysis inclusion) supporting a shift to a Class I or IIa recommendation for transitioning to DOAC monotherapy at 1 month as the new default for patients without extreme ischemic risk, fundamentally shortening the standard duration of dual therapy.

Clinical Landscape

Noteworthy Related Trials

2016

PIONEER AF-PCI

n = 2,124 · NEJM

Tested

Rivaroxaban 15mg daily + P2Y12 inhibitor

Population

Patients with non-valvular AF undergoing PCI with stenting

Comparator

Standard triple therapy (VKA + DAPT)

Endpoint

Clinically significant bleeding

Key result: Rivaroxaban-based dual therapy significantly reduced the rate of clinically significant bleeding compared to standard triple therapy.

2017

RE-DUAL PCI

n = 2,725 · NEJM

Tested

Dabigatran (110mg or 150mg BID) + P2Y12 inhibitor

Population

Patients with non-valvular AF who had undergone PCI

Comparator

Warfarin triple therapy (VKA + aspirin + P2Y12 inhibitor)

Endpoint

ISTH major or clinically relevant nonmajor bleeding

Key result: Dabigatran dual therapy significantly reduced bleeding risk compared to warfarin triple therapy while being non-inferior for thromboembolic events.

2019

AUGUSTUS Trial

n = 4,614 · NEJM

Tested

Apixaban plus P2Y12 inhibitor without aspirin

Population

Patients with AF and a recent ACS or undergoing PCI

Comparator

Vitamin K antagonist and/or aspirin

Endpoint

ISTH major or clinically relevant nonmajor bleeding

Key result: An antithrombotic regimen of apixaban without aspirin resulted in significantly less bleeding and fewer hospitalizations than regimens containing VKA, aspirin, or both.

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