Impact of frailty models on the prescription of oral anticoagulants and on the incidence of stroke, bleeding, and mortality in older patients with atrial fibrillation: a systematic review

Background: Frailty is common in older patients with atrial fibrillation (AF). Current guidelines recommend oral anticoagulant therapy (OAT) except in case of severe frailty or reduced life expectancy, but definitive evidence on which "frailty" tools may help to identify older AF patients expected to derive little or no benefit from OAT is still lacking. Some persistent uncertainties may derive from the different clinical implications that the two major models of frailty, namely the frail phenotype (FP) and the deficit accumulation model (DAM), underlie. We thus conducted a systematic review of published studies to examine the association of the presence of frailty, cate-gorized according to the FP and DAM, with 1) OAT prescription and 2) incidence of clinical outcomes (all-cause mortality, stroke and/or systemic embolism and major or clinically relevant non-major bleeding) in patients receiving OAT.Methods: Embase and MEDLINE were searched from inception until May 31st, 2022, for studies using a validated tool to identify frailty in subjects aged 65 years or older with a diagnosis of non-valvular AF; only studies on patients prescribed an OAT were considered eligible for the analyses involving clinical outcomes. The protocols for each review question have been registered in PROSPERO database (CRD42022308623 and CRD42022308628).Findings: Twenty-three studies exploring the association between frailty and OAT prescription on a total of 504 719 subjects were included. Patients with increasing severity of DAM frailty showed consistently lower OAT prescription rates than non-frail patients, whereas use of OAT did not significantly differ between patients with the FP compared with non-frail subjects. Eleven studies exploring the association between frailty and clinical outcomes on a total of 41 985 individuals receiving oral anticoagulation were included. Compared with non-frail subjects, a higher risk of all-cause mortality and clinical outcomes could be observed for AF patients prescribed with OAT with severe frailty according to the DAM, with inconclusive findings for the FP. High levels of het-erogeneity were observed in both groups of studies; therefore, a meta-analysis was not performed.Conclusions: Due to the great heterogeneity among different validated frailty measures, indiscriminately relying on "frailty" should not be regarded as the gold standard for clinical decision-making about stroke prevention in older AF patients. Present findings suggest that severe frailty according to the DAM is associated with less use of OAT and increased risk of all-cause mortality, thereby representing at the moment the most reasonable tool to efficiently recognize patients with limited life expectancy and for whom there is so far scant, if any, evidence of a clinical benefit of OAT.