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PHILADELPHIA -- For patients with subclinical atrial fibrillation (Afib, AF) detected by their pacemaker or defibrillator, direct oral anticoagulation brought their already low stroke risk even lower -- but at a cost in bleeding events, the ARTESiA trial showed.

Apixaban (Eliquis) treatment cut risk of stroke or systemic embolism 37% compared with low-dose aspirin over a mean follow-up of 3.5 years, albeit with a small absolute difference (0.78% vs 1.24% per patient-year, P=0.007), Jeff S. Healey, MD, of McMaster University in Hamilton, Ontario, reported at the American Heart Association meeting annual meeting. The study was also published simultaneously in the .

But risk of major bleeding counterbalanced that benefit, at 1.71% per patient-year with apixaban versus 0.94% per patient-year with aspirin (HR 1.80, 95% CI 1.26-2.57) in the as-treated population with Afib episodes of 6 minutes to 24 hours and elevated stroke risk characteristics.

Benefit-to-risk analysis suggested that taking apixaban in lieu of aspirin would prevent 4.6 strokes or systemic embolic events at the cost of 4.1 major bleeds per 1,000 person-years.

"We feel that in patients with subclinical atrial fibrillation, clinicians should consider the use of oral anticoagulation in folks ... with additional stroke risk factors," Healey said.

These events are detected in about one-third of patients with implanted cardiac devices, and it's a common conundrum of how to treat them.

Guidelines don't recommend any anticoagulation, even though studies have suggested a slight increased stroke risk, noted late-breaking clinical trial session study discussant Christine M. Albert, MD, MPH, of Cedars-Sinai Medical Center in Los Angeles.

While the reduction in stroke risk appears real, "the question is, 'Is that worth it for the bleeding risk?'" she said at a press conference.

She pointed out that the greater bleeding risk of apixaban was in comparison to aspirin, which itself carries bleeding risk with a number needed to harm of about 210. "So the relative risk of bleeding will maybe even be higher" if compared to placebo.

Placebo was the comparator in the NOAH-AFNET 6 trial, which recently reported that edoxaban (Savaysa) didn't significantly improve outcomes for high-risk patients with subclinical Afib-like episodes detected by implanted cardiac devices.

Albert noted the similar hazard ratio in that trial (0.81) for a fairly similar design, albeit without an upper limit on the duration of an atrial rate of ≥170 bpm. Enrollment criteria were at least 6 minutes and at least one additional risk factor for stroke but no history of clinical Afib on electrocardiogram.

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). 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 so patients could be on definite anticoagulation.

Healey's group also presented a meta-analysis of NOAH-AFNET 6 and ARTESiA at the meeting, also published in , showing that oral anticoagulation significantly reduced risk of ischemic stroke (RR 0.68, 95% CI 0.50-0.92) and a composite of cardiovascular death, all-cause stroke, peripheral arterial embolism, myocardial infarction or pulmonary embolism (RR 0.85, 95% CI 0.73-1.00).

Regarding the difference between the trials, "[t]he most likely explanation is a lack of power in the prematurely ended NOAH-AFNET 6 trial, and the inclusion of death from cardiovascular cause in the composite outcome might have diluted effects on stroke outcome," noted Emma Svennberg, MD, PhD, of the Karolinska Institute in Stockholm in an accompanying the ARTESiA paper.

She argued for "shared decision making before oral anticoagulant treatment, management of modifiable bleeding risks and coexisting conditions, and close monitoring of progression to clinical atrial fibrillation."

When the ARTESiA trial session panel was asked about what they would do for these device-detected atrial high rate episodes after heading home from the meeting, the consensus was largely conservative.

"The only thing that will move me will be likely if there's a high risk or some other driver," said Manesh Patel, MD, of the Duke Clinical Research Institute in Durham, North Carolina. "We have 40% of patients with known clinical AF that aren't getting treated with oral anticoagulation ... So we have a lot of opportunity in patients in our practices to get those anticoagulated. Their risk is higher."

Alberts agreed, "Given the risk-benefit ratio, there needs to be pause and further consideration by expert guideline committees before implementing this therapy in patients with [subclinical Afib] less than 24 hours." With further study, though, it's possible that either a higher stroke-risk group or a lower bleeding risk group could be identified who should be treated, she suggested.

However, Elaine Hylek, MD, MPH, of Boston Medical Center, countered: "No one wants to have bleeding because that's when patients stop these agents. But I would just challenge that 1% is just too low to be thinking about treatment, because I think one in 100 isn't trivial."

Albert emphasized that the results do not apply to Afib detected on a smartwatch or similar wearable consumer device. The showed a net benefit from screening for Afib with such devices, but the "tiny, not impressive" benefit was in a vastly different population, she noted.

"My instructions are turn off the EKG monitor on your watch," she told 麻豆传媒, "because I don't know what to do with that."