Apixaban’s Role in Stroke Prevention

American Heart Association Scientific Sessions 2023, latest scientific summary on LBS.05

Summary

Background

Subclinical atrial fibrillation is short-lived and asymptomatic and can usually only be detected by long-term continuous monitoring with pacemakers or defibrillators. Subclinical atrial fibrillation is associated with an increased risk of stroke by a factor of 2.5; however, the benefit of oral anticoagulation treatment is uncertain.

Methods

We conducted a trial with patients with subclinical atrial fibrillation that lasted from 6 minutes to 24 hours.

Patients were randomly assigned in a double-blind, double-dummy design to receive apixaban at a dose of 5 mg twice daily (2.5 mg twice daily when indicated) or aspirin at a dose of 81 mg daily. Trial medication was discontinued and anticoagulation initiated if subclinical atrial fibrillation lasting more than 24 hours or clinical atrial fibrillation developed.

The primary efficacy outcome, stroke or systemic embolism, was assessed in the intention-to-treat population (all patients who had been randomized); The primary safety outcome, major bleeding, was assessed in the treatment population (all patients who had undergone randomization and received at least one dose of assigned trial drug, with follow-up censored 5 days after permanent discontinuation). of trial medication for any reason).

Results

4,012 patients were included with a mean age (± SD) of 76.8 ± 7.6 years and a mean CHA 2 DS 2 -VASc score of 3.9 ± 1.1 (scores range between 0 and 9, and higher scores indicate a higher risk of stroke); 36.1% of the patients were women.

After a mean follow-up of 3.5 ± 1.8 years, stroke or systemic embolism occurred in 55 patients in the apixaban group (0.78% per patient-year) and in 86 patients in the aspirin group (1, 24% per patient-year) (hazard ratio, 0.63; 95% confidence interval [CI], 0.45 to 0.88; P = 0.007).

In the treatment population, the rate of major bleeding was 1.71% per patient-year in the apixaban group and 0.94% per patient-year in the aspirin group (hazard ratio, 1.80; 95% CI, 1.26 to 2.57; P = 0.001).

Fatal hemorrhage occurred in 5 patients in the apixaban group and 8 patients in the aspirin group.

(Funded by the Canadian Institutes of Health Research and others; ARTESIA ClinicalTrials.gov number, NCT01938248. opens in new tab.)

Comments

The blood-thinning drug apixaban reduced the rate of strokes and blood clots among adults with implanted cardiac devices who experienced brief episodes of asymptomatic, irregular heart rhythms compared with adults who took aspirin, according to a breaking report. science presented today at the American Heart Association’s 2023 Scientific Sessions. The meeting, to be held November 11-13 in Philadelphia, is a major global exchange of the latest scientific advances, research and evidence-based clinical practice updates in cardiovascular science. The full manuscript is also published simultaneously today in The New England Journal of Medicine.

The medication was associated with significant bleeding; However, it did not endanger his life.

Atrial fibrillation (AFib) is an irregular heartbeat that can cause blood clots, stroke, heart failure, or other heart-related complications. It may occur without symptoms or be so brief that it is difficult to detect. Subclinical atrial fibrillation is a brief, asymptomatic atrial fibrillation that is detected by pacemakers, implantable defibrillators, and heart monitors that record a person’s heart rate continuously and detect these brief episodes of irregular heartbeats.

Previous research has indicated that treatment with oral anticoagulant medications (also known as blood thinners) can prevent up to two-thirds of strokes in people diagnosed with atrial fibrillation. However, blood-thinning medications, including apixaban, cause an increased risk of serious bleeding, including blood in the stool or urine, and/or bleeding related to trauma.

"We have observed in previous research that the magnitude of stroke risk associated with short-duration, asymptomatic, subclinical atrial fibrillation was lower than that seen in people with longer duration, symptomatic atrial fibrillation," said study author Jeff Healey. , M.D., M.S. director of the division of cardiology and professor of medicine at McMaster University in Hamilton, Ontario, Canada. "So that’s a different risk-benefit consideration when prescribing blood thinners."

This phase 4 clinical trial, called “Apixaban for Reduction of Thromboembolism in Patients with Device-Detected Subclinical Atrial Fibrillation (ARTESIA),” examined the risk-benefit considerations of treating asymptomatic atrial fibrillation. Researchers enrolled more than 4,000 adults from 16 countries in North America and Europe who had been implanted with a pacemaker, a defibrillator, or a cardiac monitor that detected asymptomatic atrial fibrillation.

Half of the participants were randomly assigned to receive an anticoagulant (the standard treatment for patients with stroke risk factors who have clinical atrial fibrillation); specifically, 5 mg of apixaban, twice daily or 2.5 mg twice daily in patients who meet pre-established criteria for dose reduction, such as being over 80 years of age or weighing less than 132 pounds). The other half of the participants received 81 mg of aspirin daily. Neither the participants nor the researchers knew what medications the participants were taking. Researchers monitored study participants for an average of 3.5 years for strokes, blood clots and/or serious bleeding.

The investigation found:

People in the apixaban treatment group had an overall 37% reduction in the incidence of strokes or blood clots, driven primarily by a 51% reduction in fatal or disabling strokes.

Among patients actively taking study medication, the risk of major bleeding was 74% higher in the apixaban group compared with the aspirin group (1.69% per year vs. 0.96% per year).

Nominally, fewer major bleeds in the apixaban group presented with neurological symptoms or critically low blood pressure (18.5% vs. 26%) or were fatal at presentation (1.1% vs. 4%). Less than 10% of bleeds required life-saving intervention such as surgery (9.8% in the apixaban group and 8% in the aspirin group).

There were no differences in more serious bleeds between participants treated with aspirin and those treated with apixaban, such as fatal bleeds, bleeds that required surgery, or bleeds that required blood transfusion.

In this trial, the rate of major bleeding was 1.69% per year in the apixaban group, which is similar to or lower than expected based on previous major studies of these drugs to treat Fib, according to Healey.

“Currently, there is no consistent guidance on how to treat subclinical atrial fibrillation in people with implanted cardiac devices. “I think the ARTESIA results are strong enough to change the way we practice and lead to changes in management guidelines, so we recommend that many of these people who have subclinical AFib receive an anticoagulant,” Healy said. "The study findings will also help address current questions about the potential value of population screening for AFib."

Future studies by these researchers and others will delve into tailoring therapy by determining whether there are subgroups of people who are at higher or lower risk for stroke, blood clots, and/or bleeding.

Notably, this study did not directly address the question of whether the millions of people with consumer technologies, including smart watches, smart rings, and smartphones that can detect brief episodes of atrial fibrillation, should be treated with an anticoagulant. medicine.

Limitations of the study include that only people with implanted cardiac devices were enrolled in the trial and that the approach to aspirin therapy changed somewhat over the years of the trial. Aspirin used to be a recommended therapy for stroke prevention in people with atrial fibrillation, particularly those at lower risk, Healy explained. After the ARTESIA study was designed, this recommendation fell out of favor. Additionally, over the past 10 years, there has been a sharp decline in the combined use of aspirin in addition to oral anticoagulants, as other studies have shown no incremental benefit of aspirin but a doubling in the rate of major bleeding.