In patients with subclinical AF, apixaban reduces stroke risk, raises bleeding risk
Click Here to Manage Email Alerts
Key takeaways:
- In patients with subclinical atrial fibrillation, apixaban lowered risk for stroke and systemic embolism vs. aspirin.
- Apixaban increased major, but not fatal or intracranial, bleeding compared with aspirin.
PHILADELPHIA — In patients with subclinical atrial fibrillation, apixaban lowered risk for stroke but increased risk for bleeding compared with aspirin, according to the results of the ARTESIA trial.
“Subclinical atrial fibrillation ... refers to brief episodes of atrial fibrillation [that] are asymptomatic and detected only with long-term continuous monitoring, typically via a pacemaker or implanted defibrillator,” Jeff S. Healey, MD, senior scientist at the Population Health Research Institute, a joint research institute of McMaster University and Hamilton Health Sciences in Hamilton, Ontario, Canada, said during a press conference at the American Heart Association Scientific Sessions. “These are present in approximately one-third of individuals with these devices and are associated with a 2.5-fold increase in the risk of stroke. This is a lower relative risk increase than seen with clinical atrial fibrillation; thus, we have questioned the value for oral anticoagulation to treat this type of atrial arrhythmia.”
Image: Adobe Stock
The researchers randomly assigned 4,012 patients (mean age, 77 years; 36% women; mean CHA2DS2-VASc score, 3.9) with subclinical AF lasting 6 minutes to 24 hours to apixaban (Eliquis, Bristol Myers Squibb/Pfizer) 5 mg twice daily (or 2.5 mg twice daily if indicated) or aspirin 81 mg daily.
If a patient developed subclinical AF lasting more than 24 hours or clinical AF, their trial medication was stopped and anticoagulation was started, Healey said.
The researchers assessed the primary efficacy endpoint of stroke or systemic embolism in an intention-to-treat population consisting of all patients who underwent randomization and assessed the primary safety endpoint of major bleeding in an on-treatment population consisting of all patients who underwent randomization and received at least one dose of the assigned trial drug, with follow-up censored 5 days after permanent discontinuation of trial medication for any reason. Mean follow-up was 3.5 years.
The results were simultaneously published in The New England Journal of Medicine.
During the study period, the primary efficacy outcome occurred at a rate of 0.78% per patient-year in the apixaban group and 1.24% per patient-year in the aspirin group (HR = 0.63; 95% CI, 0.45-0.88; P = .007), Healey said during the press conference, noting severe strokes (modified Rankin Scale score, 3-6) were reduced by about half (HR = 0.51; 95% CI, 0.29-0.88).
The primary safety outcome occurred at a rate of 1.71% per patient-year in the apixaban group and 0.94% per patient-year in the aspirin group (HR = 1.8; 95% CI, 1.26-2.57; P = .001), he said.
Fatal bleeding was infrequent, occurring in five patients from the apixaban group and eight from the aspirin group, he said. The HR for major bleeding in the intention-to-treat analysis was 1.36 (95% CI, 1.01-1.82; P = .04).
CV death did not differ between the groups (HR = 0.96; 95% CI, 0.73-1.25), according to the researchers.
In a benefit-to-risk analysis, apixaban was linked to 4.6 fewer strokes/emboli per 1,000 patient-years and 4.1 more major bleeds per 1,000 patient-years in the intention-to-treat population and to 5.8 fewer strokes/emboli per 1,000 patient-years and 7.7 more major bleeds per 1,000 patient-years in the as-treated population.
He noted that apixaban reduced permanently disabling or fatal strokes by 49% compared with aspirin.
“Compared to aspirin, the ARTESIA trial shows that apixaban can, in fact, reduce stroke among patients with subclinical atrial fibrillation, and it reduces the more severe types of stroke by approximately half,” Healey said during the press conference. “There is an increase in major bleeding, but no measured increase in intracranial bleeding or fatal bleeding. Overall, given the balance of events, we felt that anticoagulation should be considered among patients with subclinical atrial fibrillation and additional stroke risk factors.”
Reference:
Perspective
Back to Top
Christine M. Albert, MD, MPH, FHRS, FACC
There are a lot of questions that remain for this issue. I was not surprised that the researchers found a benefit of oral anticoagulation on stroke in this population. If you look at the NOAH-AFNET 6 study, the researchers found a similar effect, but they had half the endpoints. It’s pretty clear that with AF, if you anticoagulate it, you get less stroke. What is left to question is that the number needed to treat/number needed to harm does not work out too well in a broad population because the risk for stroke was so low. Was there a group inside that has a higher risk for stroke in whom you would want to initiate that therapy?
Clinical AF has five times the risk for stroke as subclinical AF. This is a very different population. In some ways, it is reassuring to be able to talk to a patient, show them these data and tell them that their risk for stroke is probably pretty low. What I am hesitant about is that the control arm was not placebo, it was aspirin. And aspirin causes bleeding, so I can’t really say to a patient that they should switch from something that already causes bleeding to something that causes more bleeding. It’s a tough issue.
Collapse
Healey JS, et al. LBS.05. Shocking decisions in AFib care. Presented at: American Heart Association Scientific Sessions; Nov. 11-13, 2023; Philadelphia.
Click Here to Manage Email Alerts