Cerebral Microbleeds, Anemia, and Estimated Net Benefit of DOACs versus Warfarin in Older Atrial Fibrillation: A Single-Center MRI-Selected Cohort.

BACKGROUND

Randomized trials favor direct oral anticoagulants (DOACs) over warfarin for eligible atrial fibrillation (AF), but whether cerebral microbleeds (CMBs) and anemia identify older patients with narrower benefit-harm margins remain uncertain. We estimated 2-year net clinical benefit (NCB) overall and by CMB/anemia strata.

METHODS

This single-center, MRI-selected prospective observational cohort included patients aged ≥65 years with non-valvular AF receiving a DOAC or warfarin. Follow-up began at susceptibility MRI; CMB presence (0 vs ≥1) was rated by two blinded raters, and anemia used World Health Organization hemoglobin thresholds. DOAC-warfarin associations were estimated using propensity-score overlap weighting and competing-risk models for ischemic stroke/systemic embolism (IS/SE) and intracranial hemorrhage (ICH). Two-year NCB was expressed as net events prevented per 1000 with bootstrap 95% confidence intervals (CIs).

RESULTS

Among 797 patients (DOAC n=517; warfarin n=280), 31.0% had ≥1 CMB and 33.8% had anemia. During 2463 person-years, 40 first IS/SE events, 22 first ICH events, and 89 deaths occurred as first components of net adverse clinical events (NACE). After weighting, DOAC use was associated with lower NACE (2-year risk 14.9% vs 21.8%; hazard ratio 0.69, 95% CI 0.52-0.91), ICH (1.4% vs 4.3%; subdistribution hazard ratio 0.39, 95% CI 0.21-0.72), and IS/SE (3.9% vs 6.4%; subdistribution hazard ratio 0.63, 95% CI 0.41-0.96). Estimated NCB favored DOACs overall (67.0/1,000; 95% CI 28.4-102.7) and was attenuated in patients with both CMBs and anemia (38.0/1,000; 95% CI 4.2-71.5).

CONCLUSIONS

DOAC use was associated with a favorable estimated 2-year NCB vs warfarin in this MRI-selected cohort. Combined CMB/anemia findings are exploratory and hypothesis-generating and should not guide prescribing without multicenter validation.