Direct Oral Anticoagulants for Stroke Prevention in Patients With Device-Detected Atrial Fibrillation: A Study-Level Meta-Analysis of the NOAH-AFNET 6 and ARTESiA Trials

Abstract

Background: Device-detected atrial fibrillation (AF) (also known as subclinical AF or atrial high-rate episodes) is a common finding in patients with an implanted cardiac rhythm device and is associated with an increased risk of ischemic stroke. Whether oral anticoagulation is effective and safe in this patient population is unclear. Methods: We performed a systematic review of MEDLINE and Embase for randomized trials comparing oral anticoagulation to antiplatelet or no antithrombotic therapy in adults with device-detected AF recorded by a pacemaker, implantable cardioverter-defibrillator, cardiac resynchronization therapy device or implanted cardiac monitor. We used random-effects models for meta-analysis and rated the quality of evidence using the GRADE framework. The review was pre-registered (PROSPERO CRD42023463212). Results: From 785 unique citations, we identified two randomized trials with relevant clinical outcome data; NOAH-AFNET 6 (2,536 participants) evaluated edoxaban and ARTESiA (4,012 participants) evaluated apixaban. Meta-analysis demonstrated that oral anticoagulation with these agents reduced ischemic stroke (relative risk [RR] 0.68, 95% confidence interval [CI] 0.50-0.92; high-quality evidence). The results from the two trials were consistent (I 2 statistic for heterogeneity=0%). Oral anticoagulation also reduced a composite of cardiovascular death, all-cause stroke, peripheral arterial embolism, myocardial infarction or pulmonary embolism (RR 0.85, 95% CI 0.73-1.00, I 2 =0%; moderate-quality evidence). There was no reduction in cardiovascular death (RR 0.95, 95% CI 0.76-1.17, I 2 =0%; moderate-quality evidence) or all-cause mortality (RR 1.08, 95% CI 0.96-1.21 I 2 =0%; moderate-quality evidence). Oral anticoagulation increased major bleeding (RR 1.62, 95% CI 1.05-2.5 I ² =61%; high-quality evidence). Conclusions: The results of the NOAH-AFNET 6 and ARTESiA trials are consistent with each other. Meta-analysis of these two large randomized trials provides high-quality evidence that oral anticoagulation with edoxaban or apixaban reduces the risk of stroke in patients with device-detected AF and increases the risk of major bleeding.

What Do We Really Know About the Effect of Prolonged Heart Rhythm Monitoring After Stroke?

“…As with NOAH-AFNET 6, the rate of ischemic stroke was low at only 1.2% per year in the comparator arm, which was also confirmed by a study-level meta-analysis of the 2 trials. 13 Together, LOOP, NOAH-AFNET 6, and ARTESiA confirm that the most common type of AF detected on an ILR—subclinical AF—confers a lower stroke risk and less clear net benefit from OAC compared with clinically diagnosed AF.…”

Embolic strokes of undetermined source: a clinical consensus statement of the ESC Council on Stroke, the European Association of Cardiovascular Imaging and the European Heart Rhythm Association of the ESC

“… 62 , 63 In the study-level meta-analysis of these two trials, there was significant reduction in the rate of ischaemic stroke with OAC [relative risk (RR) 0.68; 95% CI 0.50–0.92, with no sign of heterogeneity) and significant increase in the rate of major bleeding (RR 1.62; 95% CI 1.05–2.5). 67 The duration of AHRE did not interact with the efficacy or safety of anticoagulation, either using the 24-h threshold or as a continuous covariate in the NOAH-AFNET 6 trial. 68 Only 9.4% of included patients had previous stroke/TIA or systemic embolism.…”

Straining the Limits: Atrial Imaging to Predict Subclinical Atrial Fibrillation

“…The ARTESIA trial (Apixaban for the Reduction of Thrombo-Embolism in Patients with Device-Detected Subclinical Atrial Fibrillation Trial) and concomitant systematic meta-analysis demonstrated a lower risk of stroke or systemic embolism (albeit a higher risk of major bleeding) with oral anticoagulation in patients with SCAF. 9,10 The role of screening for SCAF using left atrial strain or any other imaging approach (as opposed to detecting SCAF with monitoring), however, is unclear. 11,12 In patients with cryptogenic stroke, where the rate of SCAF is likely ≈30%, oral anticoagulation did not decrease the risk of recurrent stroke.…”