PDF: ARTESIA
(2024)Objective
Determine whether apixaban results in a lower risk of stroke or systemic embolism than aspirin, with an acceptably low risk of major bleeding, in patients with device-detected subclinical atrial fibrillation (SCAF).
Study Summary
Intervention
Randomized, double-blind, double-dummy trial conducted at 247 sites in 16 European and North American countries. N=4012 adults with device-detected subclinical AF (at least one episode 6 min to 24 h) and CHA2DS2-VASc score ≥3 (minimum age 55; patients ≥75 years or with prior stroke could enroll without additional risk factors). Randomized to: • Apixaban 5 mg BID (2.5 mg BID when indicated) — n=2015 • Aspirin 81 mg daily — n=1997 Mean follow-up 3.5±1.8 years.
Study Design
Arms: Apixaban 5 mg BID (n=2015) vs Aspirin 81 mg daily (n=1997)
Outcome
• Ischemic or unknown-cause stroke: HR 0.62 (95% CI 0.43–0.91)
• Stroke from any cause: HR 0.64 (95% CI 0.46–0.90)
• Disabling or fatal stroke (mRS 3–6): 18/55 (33%) apixaban vs 36/84 (43%) aspirin; HR 0.51 (95% CI 0.29–0.88)
• Primary safety — major bleeding (on-treatment): apixaban 1.71%/yr vs aspirin 0.94%/yr; HR 1.80 (95% CI 1.26–2.57); P=0.001
• Fatal bleeding (on-treatment): 5 apixaban vs 8 aspirin
• Symptomatic intracranial hemorrhage (on-treatment): 12 apixaban vs 15 aspirin
• GI bleeding (ITT, major): HR 1.76 (95% CI 1.13–2.74)
• No significant subgroup interactions observed
Bottom Line
Among patients with subclinical atrial fibrillation, apixaban significantly reduced the risk of stroke or systemic embolism compared to aspirin, but it was associated with a higher risk of major bleeding. The choice between apixaban and aspirin should be individualized based on the patient's bleeding risk.
Major Points
- 4012 patients with subclinical atrial fibrillation lasting 6 minutes to 24 hours were randomly assigned to apixaban (5 mg twice daily or 2.5 mg twice daily when indicated) or aspirin (81 mg daily).
- Mean follow-up was 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) (HR, 0.63; 95% CI, 0.45 to 0.88; P=0.007).
- The rate of major bleeding in the on-treatment population was 1.71% per patient-year in the apixaban group and 0.94% per patient-year in the aspirin group (HR, 1.80; 95% CI, 1.26 to 2.57; P=0.001).
- Fatal bleeding occurred in 5 patients in the apixaban group and 8 patients in the aspirin group.
- The risk of disabling or fatal stroke was lower by 49% with apixaban than with aspirin (HR, 0.51; 95% CI, 0.29 to 0.88).
- The data strongly suggest apixaban prevents stroke in this population, despite a high rate of trial-drug discontinuation.
- No significant subgroup interactions were observed.
Study Design
- Study Type
- Randomized, double-blind, double-dummy, controlled trial
- Randomization
- Yes
- Blinding
- Double-blind (patients received matching placebos for the alternate treatment; committees adjudicating outcomes were unaware of trial-group assignments).
- Sample Size
- 4012
- Follow-up
- Mean 3.5±1.8 years
- Centers
- 247
- Countries
- 16 European and North American countries
Primary Outcome
Definition: Composite of stroke and systemic embolism, assessed in the intention-to-treat population (with censoring of follow-up once subclinical atrial fibrillation lasting >24 hours or clinical atrial fibrillation developed).
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 86 patients (1.24% per patient-year) | 55 patients (0.78% per patient-year) | 0.63 (0.45 to 0.88) | 0.007 |
Limitations & Criticisms
- The trial did not reach its target of 248 primary-outcome events: although planned enrollment of 4000 was exceeded (4012 randomized), slow accrual and a lower-than-expected event rate meant the event goal was unmet, and final follow-up visits were triggered when trial medication could no longer be resupplied — potentially limiting power to detect smaller clinically relevant differences.
- The primary efficacy outcome analysis censored follow-up once subclinical AF lasting >24 hours or clinical AF developed, which could potentially bias the results.
- The study primarily included patients with pacemakers, defibrillators, or cardiac monitors, which may limit generalizability to patients without such implanted devices.
- The risk of major bleeding was higher with apixaban, which must be carefully balanced against the benefit in stroke prevention.
- The trial's findings may not be fully generalizable to younger patients, as the mean age was 76.8 years.
Citation
N Engl J Med 2024;390:107-17.