Written by Samuel Rouleau
A meta-analysis of over 70,000 patients found that non-vitamin-K antagonists (NOACs) were slightly more effective at preventing systemic embolic events (SEE) than warfarin in patients with atrial fibrillation (AF).
Clots, clots, clots—everywhere!
Typically, ischemic stroke risk is the focus in patients with AF, but SEE can have similar morbidity and mortality. In fact, the 30-day mortality rate for patients after SEE was 18%, compared to 17% after ischemic stroke. For this meta-analysis, SEE was defined as acute arterial insufficiency with confirmed (clinical or radiographic) evidence of arterial obstruction not due to progressive peripheral arterial disease or instrumentation. Embolic events in the CNS (stroke), eye, heart (MI), and pulmonary circulation (PE) were NOT defined as SEEs.
Out of the 71,683 patients from included RCTs (RE-LY, ROCKET AF, ARISTOTLE, ENGAGE AF-TIMI 48), 188 patients had an SEE, approximately 8.5% of all arterial thromboembolic events. Patients on standard dose of NOAC had lower event rate per year compared to warfarin, which just met statistical significance (0.10% vs. 0.15% patient/year, HR 0.71, 95%CI 0.51–0.99, p = 0.04). Mortality after SEE in those who had been on NOACs was slightly lower than those on warfarin, which was not statistically significant (0.01% vs. 0.03% patient/year, HR 0.43, 95% CI0.18–1.05,p = 0.070). Notably, low-dose NOACs performed worse compared to standard dose with regard to SEE frequency and mortality.
How will this change my practice?
This study is a good reminder that outside of stroke, MI, and PE, we need to have a low threshold to suspect other types of arterial occlusion events in patients with AF. Standard dose NOACs continue to show good performance compared to warfarin and are largely recommended over warfarin outside specific populations (i.e. antiphospholipid syndrome).
Source
Systemic Embolic Events in Atrial Fibrillation: An Individual Patient Data Meta-analysis of 71 683 Participants Randomized to NOAC Versus Warfarin. Circulation. 2026 Feb 24;153(8):567-575. doi: 10.1161/CIRCULATIONAHA.125.075275. Epub 2026 Jan 30. PMID: 41614257.
