by Isabella Colonna
For December we have selected Healey JS, Lopes RD, Granger CB, Alings M, Rivard L, McIntyre WF, Atar D, Birnie DH, Boriani G, Camm AJ, Conen D, Erath JW, Gold MR, Hohnloser SH, Ip J, Kautzner J, Kutyifa V, Linde C, Mabo P, Mairesse G, Benezet Mazuecos J, Cosedis Nielsen J, Philippon F, Proietti M, Sticherling C, Wong JA, Wright DJ, Zarraga IG, Coutts SB, Kaplan A, Pombo M, Ayala-Paredes F, Xu L, Simek K, Nevills S, Mian R, Connolly SJ; ARTESIA Investigators. Apixaban for Stroke Prevention in Subclinical Atrial Fibrillation. N Engl J Med. 2023 Nov 12. doi: 10.1056/NEJMoa2310234. Epub ahead of print. PMID: 37952132.
Subclinical atrial fibrillation is short-lasting, asymptomatic or paucisymptomatic and usually detected only by long-term, continuous cardiac rhythm monitoring. Although it has been associated with increased risk of stroke, the role of oral anticoagulation in this pathological condition is uncertain.
This study presents the results of the Apixaban for the Reduction of Thrombo-Embolism in Patients with Device-Detected Subclinical Atrial Fibrillation (ARTESIA) trial; a multicentre, double-blind, randomised clinical trial investigating whether apixaban, compared to aspirin, would be associated with reduced risk of stroke or systemic embolism, with a tolerably low risk of major bleeding. Eligible study participants were patients with a CHA2DS2VAsc score of 3 or higher and with at least an episode of subclinical atrial fibrillation lasting between 6 minutes and 24 hours, detected by a defibrillator, an implanted pacemaker, or a cardiac monitor.
After screening for eligibility, a total of 4,012 patients were randomised to receive 5mg apixaban twice a day (n=2015) or aspirin at a dose of 81mg daily (n=1997). If subclinical atrial fibrillation persisted longer than 24 hours or if clinical atrial fibrillation occurred, the trial drug was stopped and an open-label anticoagulation was started.
The primary efficacy outcome (stroke or systemic embolism) was evaluated in the intention-to-treat analysis, whereas the primary safety outcome (major bleeding) was assessed in the on-treatment population.
Stroke or systemic embolism occurred in 55 (0.78% per patient-year) and in 86 (1.24% per patient-year) patients who were treated with apixaban and aspirin, respectively, after a mean follow-up of 3.5±1.8 years (p=0.007). In line with this, the risk of disabling or fatal (mRS≥3) stroke reduced by 49% more in the apixaban than in the aspirin group.
Regarding safety, the occurrence of major bleeding was significantly greater in the individuals who received apixaban (1.71% per patient-year) than in those treated with aspirin (0.94% per patient-year). However, the majority of the bleeding events improved with supportive care; fatal bleeding occurred only in 5 and in 8 patients in the apixaban and aspirin group, respectively.
In conclusion, the results of this trial suggest that, in patients with subclinical atrial fibrillation and risk factors for stroke, treatment with apixaban, in comparison to aspirin, is associated with lower risk of stroke or systemic embolism but greater risk of major bleeding.
