Risk of both intracerebral haemorrhage and ischaemic stroke, in elderly individual with non-valvular haemorrhage taking direct oral anticoagulants compared with warfarin; analysis of the ANAFIE Registry.

Background and AimsElderly patients with nonvalvular atrial fibrillation (NVAF) might have a higher risk of intracerebral haemorrhage. To investigate this we compared the incidence of intracranial hemorrhage and its subtypes, as well as ischemic stroke, in patients taking direct oral anticoagulants (DOACs) compared with warfarin in a real world setting. We also determined the baseline characteristics associated with both ICH and ischaemic stroke. each endpoint in elderly patients with nonvalvular atrial fibrillation (NVAF).MethodsPatients aged ≥75 years with documented NVAF enrolled in the prospective, multicenter, observational All Nippon Atrial Fibrillation in the Elderly Registry between October 2016 and January 2018 were evaluated. The co-primary endpoints were the incidence of ischemic stroke and intracranial hemorrhage. Secondary endpoints included subtypes of intracranial hemorrhage.ResultsOf 32,275 patients (13,793 women; median age, 81.0 years) analyzed, 21,585 (66.9%) were taking DOACs and 8,233 (25.5%) were taking warfarin. During the median 1.88-year follow-up, 743 patients (1.24/100 person-years) developed ischemic stroke and 453 (0.75/100 person-years) developed intracranial hemorrhage (intracerebral hemorrhage, 189; subarachnoid hemorrhage, 72; subdural/epidural hemorrhage, 190; unknown subtype, 2). The incidence of ischemic stroke (adjusted hazard ratio [aHR] 0.82, 95% confidence interval [CI] 0.70-0.97), intracranial hemorrhage (0.68, 0.55-0.83), and subdural/epidural hemorrhage (0.53, 0.39-0.72) were lower in DOAC users vs warfarin users. The incidence of fatal intracranial hemorrhage and fatal subarachnoid hemorrhage were also lower in DOAC users vs warfarin users. Several baseline characteristics other than anticoagulants were also associated with the incidence of the endpoints. Of these, history of cerebrovascular disease (aHR 2.39, 95% CI 2.05-2.78), persistent NVAF, (1.90, 1.53-2.36), and long-standing persistent/permanent NVAF (1.92, 1.60-2.30) were strongly associated with ischemic stroke; severe hepatic disease (2.67, 1.46-4.88) was strongly associated with overall intracranial hemorrhage; and history of fall within 1 year was strongly associated with both overall intracranial hemorrhage (2.29, 1.76-2.97) and subdural/epidural hemorrhage (2.90, 1.99-4.23).ConclusionsPatients aged ≥75 years with NVAF taking DOACs had lower risks of ischemic stroke, intracranial hemorrhage, and subdural/epidural hemorrhage than those taking warfarin. Fall was strongly associated with the risks of intracranial and subdural/epidural hemorrhage.Data access statementThe individual deidentified participant data and study protocol will be shared for up to 36 months after publication of the article. Access criteria for data sharing (including requests) will be decided on by a committee led by Daiichi-Sankyo. To gain access, those requesting data access will need to sign a data access agreement. Requests should be directed to yamt-tky@umin.ac.jp.