OAC-ALONE: Don't Drop Antiplatelets in AF Post-Stenting Just Yet

Neil Osterweil

October 04, 2018

SAN DIEGO — Do patients with atrial fibrillation need oral anticoagulation (OAC) with a single antiplatelet therapy (APT) a year or more after receiving a coronary stent, or would OAC alone suffice? A trial involving 111 Japanese centers tried to answer that question, but failed to overcome a statistical hurdle.

Investigators in the randomized Optimizing Antithrombotic Care in Patients with Atrial Fibrillation and Coronary Stent (OAC-ALONE) noninferiority trial calculated that they needed to enroll 2000 patients over a 1-year period to get adequate statistical power, and planned to follow the patients over 18 months.

But patient enrollment moved at a glacial pace, and the investigators eventually gave in when after 3 years only 696 patients had been enrolled, reported Yukiko Nakano, MD, Kyoto University Graduate School of Medicine, Japan.

"Noninferiority of OAC alone to combined OAC and single APT was not established for the composite primary end point of death, myocardial infarction (MI), stroke, and systemic embolism because of insufficient sample size. Therefore, the primary hypothesis of the present study was inconclusive," she said here at Transcatheter Cardiovascular Therapeutics 2018.

The study was published online in Circulation to coincide with the presentation of the data during a late-breaking clinical science session.

Although the investigators were unable to prove the noninferiority of oral anticoagulation alone in the aforementioned primary end point, the OAC-alone strategy did meet noninferiority for a secondary composite end point of the primary end point and major bleeding defined by the International Society on Thrombosis and Hemostasis (ISTH), Nakano said.

The OAC-ALONE trial was designed to answer the question of whether it's safe to forego antiplatelet therapy in patients with atrial fibrillation (AF) more than a year after coronary stenting.

Nakano noted that European Society of Cardiology guidelines consistently recommend OAC alone without antiplatelet therapy a year after stenting, on the theory that late-bleeding risk outweighs the additional risk for a cardiovascular event that could occur when antiplatelet therapy is tapered off.

Across the Atlantic, North American expert consensus documents recommend OAC alone in patients with AF who are at low risk for ischemia or thrombosis and high risk for bleeding.

However, the OAC-alone strategy in this patient population had never been studied in a randomized clinical trial, prompting the investigators to look into the question, Nakano said.

As previously noted, the investigators eventually enrolled 696 patients with AF (mean age, 75 years; 85% male) who had received coronary stents more than a year (mean, 4.5 years) before the start of OAC-ALONE.

The patients were randomly assigned to receive OAC alone or in combination with a single antiplatelet therapy, either aspirin 81 to 324 mg/day or clopidogrel 75 mg/day.

OAC could be warfarin-titrated to either a predefined International Normalized Ratio (INR) of 2.0 to 3.0 for patients younger than 70 years and 1.6 to 2.6 for patients 70 years and older, in accordance with to Japanese guidelines, or to direct oral anticoagulants (dabigatran 150 mg or 110 mg twice daily, rivaroxaban 15 mg or 10 mg once daily, apixaban 5 mg or 2.5 mg twice daily, or edoxaban 60 mg or 30 mg once daily).

On the basis of revised enrollment criteria, the protocol was amended to set a noninferiority margin of 1.5 on the hazard ratio scale for the primary and secondary end points.

The rate of primary end point events (death, MI, stroke, or systemic embolism) was 15.7% in the OAC-alone group and 13.6% in the OAC/APT group, translating into a hazard ratio of 1.16 (P for noninferiority = .20; P for superiority = .45).

The major secondary end point (the primary end point events and ISTH major bleeding) occurred in 19.5% of patients in the OAC-alone group and in 19.4% in the OAC/APT group.

In this analysis, the noninferiority definition for OAC alone was met, with a hazard ratio of 0.99 (P for noninferiority = .016; P for superiority = .96).

ISTH major bleeding occurred in 27 patients (7.8%) in the OAC-alone group and 36 patients (10.4%) in the OAC/APT group, but this difference was not statistically significant.

"There are some good reasons to think that stopping antiplatelets might be okay at 1 year," said C. Michael Gibson, MS, MD, Beth Israel-Deaconess Medical Center, Boston, the moderator of the session.

Other studies have suggested that "the platelets tend to calm down over time. On the other hand, we do know that in ACS [acute coronary syndrome] patients, thrombin generation continues to be excessive compared with normal patients," he said.

Discussant John A. Ambrose, MD, University of California, San Francisco, Fresno, said that the results "demonstrate something that I've seen over and over again, kind of a yin–yang phenomenon that you have; you reduce ischemia and thrombosis and you increase bleeding."

"There's a lot of bleeding that's under the radar. It's very annoying to the patient and perhaps they will stop the drug, although it is not listed in many of the trials because it's not 'major bleeding'," he added.

"I wouldn't actually alter clinical practice based on the trial, but I think it sets a nice platform to test this important question in an appropriately powered study," said discussant Deepak L. Bhatt, MD, MPH, Brigham & Women's Hospital, Boston.

"It does confirm, is consistent with, other studies. If you're on two agents, you're going to bleed more," he said, adding that "in the interim, it's not an unreasonable thing to continue a full-dose anticoagulant in the afib patient 12 months after a stent procedure has been performed, and drop the antiplatelet factor."

Bhatt noted that he is already comfortable prescribing anticoagulants only after 12 months in these patients, barring unusual circumstances.

OAC-ALONE was funded by Daiichi Sankyo. Nakano reported no relevant disclosures. Multiple coauthors disclosed financial relationships with Daiichi Sankyo and other companies. Gibson disclosed grant/research support, and consultant fees/honoraria/speakers bureau participation for multiple companies. Ambrose reported having nothing to disclose. Bhatt reported grant support/contract research from Daiichi Sankyo and financial support from other companies.

Transcatheter Cardiovascular Therapeutics (TCT) 2018. Presented September 24, 2018.

Circulation. Published online September 24, 2018. Abstract

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