One Month of Dual Antithrombotic Therapy May Be Enough After PCI in AF Patients

A caveat to the OPTIMA-AF trial: event rates were much lower than expected, complicating interpretation.

NEW ORLEANS, LA—Among patients with atrial fibrillation (AF) undergoing PCI, 1 month of dual therapy with a direct oral anticoagulant (DOAC) and a P2Y12 inhibitor does not undermine efficacy and results in less bleeding when compared with maintaining the combination for a year, according to results of the OPTIMA-AF trial.

The rate of death or thromboembolic events at 1 year was 5.4% with short-duration therapy and 4.5% with treatment lasting a year, a difference that fell with the noninferiority margin of 5% (P = 0.002), Yohei Sotomi, MD, PhD (University of Osaka Graduate School of Medicine, Japan), reported here at the American Heart Association (AHA) 2025 Scientific Sessions.

ISTH major or clinically relevant nonmajor bleeding, the primary safety endpoint, was significantly reduced by shortening the duration of dual antithrombotic therapy (4.8% vs 9.5%; P = 0.004).

“Patients with atrial fibrillation who receive a stent may only need 1 month of dual antithrombotic therapy, instead of 1 year,” Sotomi said at an AHA press conference. “This shorter treatment is just as effective and much safer in terms of bleeding.”

Electrophysiologist Sana Al-Khatib, MD (Duke Clinical Research Institute, Durham, NC), discussing the results at the press conference, said the trial addresses an area of clinical importance. “If we are indeed able to reduce the period of treatment with an oral anticoagulant and P2Y12 agent from 12 months to 1 month while preserving efficacy, and as a result reduce bleeding, this would be extremely beneficial to our patients,” she said.

A limitation of the trial, however, was the lower-than-expected event rate, which came in at about half of what was planned for when designing the study. The demonstrated noninferiority is somewhat reassuring, “but I feel like we need more data to confirm that finding,” said Al-Khatib.

She also emphasized a limitation acknowledged by the trial investigators, which was the inclusion of East Asian patients, who have risks of ischemic stroke and intracranial bleeding that differ from other populations.

“From my perspective, I personally won’t change my own practice based on those results,” Al-Khatib said. “But I would love to see at least one other trial that is adequately powered and that enrolls diverse populations of patients to look at this very important question.”

The OPTIMA-AF Trial

Patients with AF who require PCI often have indications for both oral anticoagulation and antiplatelet therapy, and combining antithrombotic therapies increases bleeding risks. One way to maintain efficacy in preventing thromboembolic events while limiting bleeding risks is to reduce the duration of combination therapy.

That approach was tested OPTIMA-AF, which was conducted at 75 sites in Japan. Researchers enrolled 1,088 patients (mean age 75 years; 79% men) who had AF, CAD (stable angina, unstable angina, or silent myocardial ischemia, but not MI), and an indication for PCI. Patients were randomized to 1 month of dual antithrombotic therapy with a DOAC plus a P2Y12 inhibitor, followed by DOAC monotherapy, or to 1 year of dual therapy. Aspirin could be added for up to 1 month if treating physicians considered it appropriate.

PCI involved implantation of a Xience everolimus-eluting stent (Abbott), which was performed with OCT or IVUS in nearly all cases.

At baseline, median CHA2DS2-VASc score was 4. The P2Y12 inhibitor prescribed at discharge was clopidogrel in roughly half and prasugrel in the rest. About 5% of patients received aspirin. The most commonly used DOAC was edoxaban (Savaysa; Daiichi Sankyo), prescribed to 47% of patients.

The primary efficacy endpoint was a composite of all-cause death, MI, definite stent thrombosis, stroke, or systemic embolism. The absolute difference between the 1-month and 1-year treatment groups was 0.9% (95% CI -1.7% to 3.5%). There were no significant differences between trial arms for any of the individual components of the endpoint.

Since noninferiority was met on the primary efficacy endpoint, the researchers tested for superiority on the primary safety endpoint of ISTH, finding an advantage for shorter-duration dual antithrombotic therapy (HR 0.50; 95% CI 0.31-0.80).

The efficacy and safety findings were consistent across subgroups, including those defined by baseline CHA2DS2-VASc score, Sotomi said.

He acknowledged some additional limitations aside from the lower-than-expected event rate and homogeneous patient population, pointing to the open-label design and the use of intracoronary imaging guidance for nearly all PCIs.

Impact on Practice

Manesh Patel, MD (Duke Clinical Research Institute, Durham, NC), president-elect of the AHA, highlighted a common problem in current clinical trials at the press conference: “We see lower risks than anticipated in almost all the studies we see here today because care continues to improve.”

Because the noninferiority margin and the observed event rate in OPTIMA-AF were roughly the same, noninferiority was likely to be shown, Patel said, also pointing to differences in risks between East Asian and other populations.

In his formal discussion following Sotomi’s Main Event presentation, Patel also noted that there was a numerical increase in all-cause death with shorter-duration therapy (4.1% vs 3.0), which “gives me a bit of pause.” He pointed out the difference in the primary safety endpoint was driven primarily by less clinically relevant nonmajor bleeding, with no significant difference in major bleeds.

Patel noted that the latest US atrial fibrillation guidelines give a preference for DOACs over vitamin K antagonists, in combination with antiplatelet therapy, in patients who undergo PCI and recommend early discontinuation of aspirin and ongoing treatment with oral anticoagulation and a P2Y12 therapy after the procedure to limit bleeding risks.

Moving forward, Patel said at the press conference, “I suspect what’ll happen is that we will still use dual therapy, oral anticoagulation and P2Y12 [inhibition], based on the indications.” He predicted that for patients with AF and an ACS undergoing PCI, dual antithrombotic therapy will continue to be used for 12 months. For those without an ACS, however, “I think there’s going to be a lot of de-escalation strategies that the guidelines currently do recommend.”

Based on a patient’s clinical syndrome and bleeding risks, there is now rationale, Patel said, to think about opting for 1 to 3 months of dual antithrombotic therapy in patients with AF undergoing PCI.