Frailty elements, direct oral anticoagulants and mortality risk in atrial fibrillation patients aged ≥ 80 or ≥ 90 years from the nationwide Italian START registry: a propensity score matching analysis

: This study aims to investigate the use of direct oral anticoagulants (DOACs) in elderly frail patients with atrial fibrillation (AF). In 4244 patients aged ≥ 80 years and 533 aged ≥ 90 years from the nationwide START registry, we examined factors associated with DOACs use (vs warfarin) and its association with all-cause and cardiovascular (CV) death, CV events (CVEs) and bleeding. Propensity score-matching (PSM) analysis was also performed. Mean age was 84.8 years, 54.9% were women and 64% received DOACs. Frailty elements as tendency to falls (odds ratio [OR] 0.66, p = 0.030), living alone (OR 0.74, p = 0.027) and lack of familial/social support (OR 0.74, p < 0.001) were inversely associated with DOACs use, while wheelchair use was directly associated (OR 1.57, p = 0.014). During a mean of 686 ± 538 days follow-up, 492 all-cause deaths, 110 CV deaths, 548 CVEs and 221 bleedings occurred. Multivariable Cox regression and Fine-Gray analyses showed that DOAC use inversely associated with all-cause mortality (hazard ratio [HR] 0.35, p < 0.001), CV death (subdistribution HR [sHR] 0.43, p < 0.001), CVEs (sHR 0.46, p < 0.001) but not with bleeding. These associations were confirmed after PSM and persisted between sexes, in patients with Charlson Comorbidities Index > 5 or aged ≥ 90 years. At 24 months, the number needed to treat (NNT) for all-cause, CV death and CVEs were 11.0, 40.2 and 13.4. In patients aged ≥ 90 years, NNTs were 4.2, 4.5 and 12.0. In very elderly AF patients, DOACs prescription is influenced by frailty elements. DOACs inversely associated with mortality and CVEs risk independently from age, sex and comorbidities burden.