One month of dual antithrombotic therapy may be enough for patients with atrial fibrillation (AF) and stable coronary artery disease undergoing percutaneous coronary intervention (PCI), according to a new trial conducted in Japan.

Results from the trial, dubbed OPTIMA-AF, showed 1 month of dual therapy with a P2Y12 inhibitor antiplatelet agent and a direct-acting oral anticoagulant (DOAC), followed by ongoing therapy with a DOAC alone, was noninferior to 12 months of dual therapy for prevention of thromboembolic events. However, the shorter duration of dual therapy was associated with a lower bleeding risk.

“Our results show a 0.9% difference in compromising efficacy with the 1-month dual therapy but a 4.7% reduction in bleeding safety events at 1 year, suggesting that the short-term strategy has a net clinical benefit,” Yohei Sotomi, MD, from The University of Osaka in Suita, Japan, concluded.

Sotomi presented the OPTIMA-AF trial at the recent American Heart Association (AHA) Scientific Sessions 2025.

Manesh Patel, MD, chief of the Division of Cardiology at Duke University Medical Center in Durham, North Carolina, expressed some caution in interpreting the results. He pointed out that all-cause mortality was numerically increased in the short-duration dual-therapy group and the bleeding reduction was driven by nonmajor clinically relevant bleeds.

Patel, who served as a discussant for the trial, concluded that patients with acute coronary syndrome (ACS), who were generally excluded from the trial, should still receive 12 months of dual antiplatelet/anticoagulant therapy if their bleeding risk is low, but that in patients with AF with stable coronary disease undergoing PCI, shorter duration of dual therapy could now be considered.

“We need to think about the patient’s risk overall for both ischemic and bleeding risks as to exactly when to stop the P2Y12 inhibitor,” he added.

Minimizing Antithrombotic Therapy Desirable

Sotomi explained that patients with AF undergoing PCI are at an increased risk for bleeding due to the concomitant use of oral anticoagulants and antiplatelets. He noted minimizing antithrombotic therapy would be desirable, but the optimal antithrombotic regimen within 1 year after PCI for this population has not been fully investigated.

The OPTIMA-AF trial included 1088 AF patients with coronary artery disease undergoing PCI for stable angina, unstable angina, or silent myocardial ischemia who were recruited from 75 sites in Japan.

Triple therapy consisting of aspirin, a P2Y12 inhibitor, and a DOAC was prescribed at the time of the procedure, and patients were then randomized to dual therapy with a DOAC plus a P2Y12 inhibitor for 1 month, followed by DOAC alone, or dual therapy with a DOAC plus a P2Y12 inhibitor for 12 months.

Researchers assessed primary efficacy and safety endpoints at 1 year. The primary efficacy endpoint was a composite of death or thromboembolic events, including myocardial infarction (MI), definite stent thrombosis, stroke, or systemic embolism. The primary safety endpoint was bleeding, including International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding.

The trial first aimed to show noninferiority of the shorter-duration dual therapy and, if that was achieved, then potential superiority. The noninferiority margin was set at 5%.

Of the P2Y12 inhibitors used, approximately half the patients received clopidogrel and half received prasugrel.

The most commonly used DOAC was edoxaban (46%), followed by apixaban (26%) and rivaroxaban (23%).

A primary outcome event occurred in 4.5% of the patients in the 12-month dual therapy group vs 5.4% of those in the 1-month dual therapy group, translating to an absolute difference of 0.9% with a 95% CI ranging from -1.7% to 3.5%, which was within the prespecified noninferiority margin of 5% (P = .002 for noninferiority).

A primary safety outcome event occurred in 9.5% of those in the 12-month dual-therapy group vs 4.8% of those in the 1-month dual-therapy group, giving an absolute difference of 4.7%, with a hazard ratio of 0.50 (95% CI, 0.31-0.8). The P value of .004 indicated superiority for the shorter course of dual therapy.

However, results did not demonstrate superiority for 1 month vs 12 months of dual therapy with respect to the primary efficacy endpoint.

Sotomi acknowledged several limitations of the trial, including its open-label design. He also noted almost all PCI procedures were performed with intracoronary guidance, which may limit generalizability to angiography-guided PCI. The event rate was also lower than expected, leading Sotomi to say that “the efficacy findings warrant cautious interpretation.” The trial’s East Asian population, which is recognized for having a distinct predisposition to ischemic and bleeding complications compared to Western populations, is a limitation as well.

Potential Clinical Implications

In his discussion of the OPTIMA-AF findings, Patel noted it is generally recommended that these patients receive 1 week of triple therapy, consisting of a DOAC, a P2Y12 inhibitor, and aspirin, followed by dropping aspirin and continuing dual therapy for some time. However, it is not clear for how long dual therapy is needed.

“While the trial did show noninferiority, I was a bit concerned that there was a numerical increase in all-cause death of 1.1% with the shorter-duration dual therapy, which gives me a bit of pause,” he commented.

“And while there was a large reduction in bleeding, this was not driven by major bleeding,” Patel added.

“So this trial shows no difference in MI, stroke, stent thrombosis, numerically maybe a little less major bleeding, but a dramatic reduction in clinically relevant nonmajor bleeding,” he said.

On how these results may translate into clinical practice, Patel said he would continue to use 12 months of dual therapy in patients with AF who were receiving a stent because of ACS if their bleeding risk was low.

“But in elective PCI patients, now we have some information on potentially stopping the P2Y12 inhibitor sooner,” he said.

Noting that other trial data had suggested 3 months as a possible optimal duration for dual therapy in these patients, Patel concluded, “Sometime between 1 and 3 months could be appropriate depending on the patient’s overall ischemic and bleeding risks.”

Sotomi reported receiving research/speaker fees from Abbott Medical Japan, Bristol-Myers Squibb, Bayer, Daiichi Sankyo, and Boehringer Ingelheim. Patel reported receiving research funding from Regeneron and Idorsia.