麻豆传媒

BOSTON -- In deciding on anticoagulation with apixaban (Eliquis) for patients with device-detected, subclinical atrial fibrillation (SCAF), one key number appeared to distinguish those for whom the benefit would outweigh the bleeding risk, an ARTESiA trial subanalysis showed.

The 39% of trial participants who had a CHA₂DS₂-VASc score under 4 had just 0.04 strokes prevented by use of apixaban versus aspirin for 3.5 years at the cost of 1.28 bleeds per 100 treated patients for a number needed to treat (NNT) of 2,500 versus a number needed to harm (NNH) of 78.

Thus, "these patients generally should not receive oral anticoagulation," Jeff Healey, MD, of McMaster University in Hamilton, Ontario, reported at the . The findings were also published in the .

For the 34% with a risk score right at 4, the numbers were flipped: 2.25 strokes prevented at the cost of just 0.05 bleeds per 100 patients treated, for an NNT of 44 versus NNH of 2,000. This group requires individualized decision making based on patient preference, Healey said.

The 27% of trial participants with a risk score over 4 had a larger benefit from apixaban but also greater risk, with 3.95 strokes prevented and 1.70 bleeds per 100 treated patients (NNT 25, NNH 59). "These patients should generally receive oral anticoagulation," Healey concluded.

"We're looking hard for [atrial fibrillation], we're finding little bits of it," he said at the late-breaking clinical trial session. "And the same is also true of the risk factors that make up the CHA₂DS₂-VASc scores. We are much more aggressive at diagnosis and treating these risk factors. So I think this analysis from ARTESiA is a good place to start."

Putting all the evidence together, session panelist Taya V. Glotzer, MD, of Hackensack University Medical Center in New Jersey, noted the big difference between clinical and subclinical atrial fibrillation (Afib or AF) in terms of risk and benefit from anticoagulation.

"The main point is that the stroke rate in the device [detected subclinical AF] trials is very, very low. The treated patients with clinical Afib had a stroke rate of 1.6%, and the untreated patients in these trials had a stroke rate lower than the treated patients [in the SCAF trials]," she said. "Prior to 2024, we knew what was black and white, we knew who to anticoagulate and who not to anticoagulate. Now we are in a gray zone, trying to balance the risk of stroke and bleeding. And I think we have to individualize. We're hoping for some studies, perhaps CHA₂DS₂-VASc scores or other information about the left atrium to help us make a decision in these patients. It's not just going to be black and white."

The main ARTESiA trial results had showed a small absolute gain from treating subclinical Afib detected by a pacemaker or defibrillator. Apixaban cut risk of stroke or systemic embolism by a relative 37% compared with low-dose aspirin over a mean follow-up of 3.5 years, but the absolute rates were 0.78% versus 1.24% per patient-year. Major bleeding counterbalanced that benefit, at 1.71% per patient-year with apixaban versus 0.94% per patient-year with aspirin in the as-treated population with Afib episodes of 6 minutes to 24 hours and elevated stroke risk characteristics.

Subclinical Afib events are detected in about one-third of patients with implanted cardiac devices. Guidelines don't recommend any anticoagulation, even though studies have suggested a slight increased stroke risk.

"However, since the average absolute risk of stroke in patients with SCAF is only 1.0-1.5% per year, clinicians are seeking more guidance on how to manage these patients," the researchers wrote. "This analysis from ARTESiA shows that the CHA₂DS₂-VASc score, the current standard for guiding the treatment of clinical AF, stratifies risk in a way that may be helpful to guide OAC [oral anticoagulation] therapy for patients with SCAF."

"However, instead of a treatment threshold for clinical AF of 1 in males and 2 in females, our results suggest a threshold of >4 for both sexes to recommend OAC for patients with SCAF," they added. Together with the recommendation against use for those with scores under 4, that gives a clear and simple guidance for nearly 70% of patients that fit the ARTESiA entry criteria.

The ARTESiA trial included 4,012 patients randomly assigned to double-blind, double-dummy treatment with apixaban (5 mg twice daily, or 2.5 mg twice daily when indicated) or aspirin (81 mg daily). Enrollment criteria included SCAF detected by an implanted pacemaker, defibrillator, or cardiac monitor; at least one episode of ≥6 minutes, but no episodes >24 hours; age at least 55 years; CHA₂DS₂-VASc score of ≥3, or any score if the patient had a history of stroke or was age 75 years or older. Patients were excluded if they had a history of clinical AF, an ongoing indication for OAC, a history of uncorrected major bleeding in the prior 6 months, or low creatinine clearance.

Mean age was 76.8, and 36% of participants were women. Mean CHA₂DS₂-VASc score was 3.9 on the 9-point scale. Subclinical atrial fibrillation lasting more than 24 hours or development of clinical atrial fibrillation prompted discontinuation of trial medication to ensure patients were on anticoagulation.

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