PDF: ARTESIA
(2024)Objective
Apixaban versus aspirin in patients with device-detected subclinical atrial fibrillation (SCAF), with a subgroup analysis of those with prior stroke or TIA.
Study Summary
Intervention
Randomized, double-blind, double-dummy trial conducted across 247 sites in 16 countries. N=4012 adults aged ≥55 years with device-detected subclinical AF (6 min to 24 h) and CHA2DS2-VASc score ≥3. Patients were randomized to: • Apixaban 5 mg BID • Aspirin 81 mg daily Subgroup analysis conducted on 346 participants with prior stroke or TIA.
Study Design
Arms: Apixaban 5 mg BID (n=2015) vs Aspirin 81 mg daily (n=1997)
Outcome
• Without prior stroke/TIA: 0.74% vs. 1.07%; HR 0.69; absolute risk reduction 1%
• Major bleeding (prior stroke/TIA): 2.26% (apixaban) vs. 1.16% (aspirin); HR 1.94
• Major bleeding (no prior stroke/TIA): 1% absolute risk increase with apixaban
• Benefit-risk profile favors apixaban for secondary prevention in subclinical AF with prior cerebrovascular events
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 was terminated early due to slow enrollment and a lower-than-expected event rate, preventing it from reaching its planned sample size and potentially limiting its power to detect smaller but 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.