Dataset Information

Oral Anticoagulants in Very Elderly Nonvalvular Atrial Fibrillation Patients With High Bleeding Risks : ANAFIE Registry

ABSTRACT:

Background

Data on the effectiveness and safety of oral anticoagulant (OAC) agents in very elderly nonvalvular atrial fibrillation patients with high bleeding risk are lacking.

Objectives

This study examined 2-year outcomes and effects of OAC agents among these patients using the ANAFIE (All Nippon Atrial Fibrillation in the Elderly) registry (N = 32,275) data.

Methods

Patients were classified into high-risk (age: ≥80 years; CHADS2 score: ≥2; and presence of ≥1 bleeding risk factor: creatinine clearance of 15-30 mL/minute, prior bleeding at critical sites, body weight of ≤45 kg, or continuous antiplatelet use) and reference groups.

Results

In the high-risk (n = 7,104) and reference (n = 25,171) group patients, 89.0% and 93.4%, respectively, used OAC agents. Of these, respectively, 30.1% and 24.2% used warfarin, and 58.9% and 69.1% used direct-acting OAC (DOAC) agents. Compared with the reference group, the high-risk group had higher incidences of stroke/systemic embolism, major bleeding, intracranial hemorrhage, gastrointestinal bleeding, cardiovascular events, and all-cause death. In the high-risk group, DOAC agent use vs nonuse of OAC agents was associated with reduced incidences of stroke/systemic embolism (HR: 0.53; 95% CI: 0.36-0.79) and all-cause death (HR: 0.65; 95% CI: 0.52-0.81) but not with major bleeding (HR: 1.09; 95% CI: 0.63-1.89). DOAC agents were superior to warfarin in effectiveness and safety. For high-risk patients, history of major bleeding, severe liver dysfunction, and falls within 1 year were independent risk factors for major bleeding.

Conclusions

High-risk elderly nonvalvular atrial fibrillation patients had higher event incidences. DOAC agents were associated with reduced risk of stroke/systemic embolism and all-cause death vs nonuse of OAC agents or warfarin. (Prospective Observational Study in Late-Stage Elderly Patients With Nonvalvular Atrial Fibrillation [ANAFIE registry]; UMIN000024006) Central Illustration

SUBMITTER: Okumura K

PROVIDER: S-EPMC9700004 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Project description:BackgroundWe determined the long-term event incidence among elderly patients with nonvalvular atrial fibrillation in terms of history of stroke/transient ischemic attack (TIA) and oral anticoagulation.MethodsPatients aged ≥75 years with documented nonvalvular atrial fibrillation enrolled in the prospective, multicenter, observational All Nippon Atrial Fibrillation in the Elderly Registry between October 2016 and January 2018 were divided into 2 groups according to history of stroke/TIA. The primary end point was the occurrence of stroke/systemic embolism within 2 years, and secondary end points were major bleeding and all-cause death within 2 years. Cox models were used to determine whether there was a difference in the hazard of each end point in patients with/without history of stroke/TIA, and in ischemic stroke/TIA survivors taking direct oral anticoagulants versus those taking warfarin.ResultsOf 32 275 evaluable patients (13 793 women [42.7%]; median age, 81.0 years), 7304 (22.6%) had a history of stroke/TIA. The patients with previous stroke/TIA were more likely to be male and older and had higher hazard rates of stroke/systemic embolism (adjusted hazard ratio, 2.25 [95% CI, 1.97-2.58]), major bleeding (1.25, 1.05-1.49), and all-cause death (1.13, 1.02-1.24) than the other groups. Of 6446 patients with prior ischemic stroke/TIA, 4393 (68.2%) were taking direct oral anticoagulants and 1668 (25.9%) were taking warfarin at enrollment. The risk of stroke/systemic embolism was comparable between these 2 groups (adjusted hazard ratio, 0.90 [95% CI, 0.71-1.14]), while the risk of major bleeding (0.67, 0.48-0.94), intracranial hemorrhage (0.57, 0.39-0.85), and cardiovascular death (0.71, 0.51-0.99) was lower among those taking direct oral anticoagulants.ConclusionsPatients aged ≥75 years with nonvalvular atrial fibrillation and previous stroke/TIA more commonly had subsequent ischemic and hemorrhagic events than those without previous stroke/TIA. Among patients with previous ischemic stroke/TIA, the risk of hemorrhagic events was lower in patients taking direct oral anticoagulants compared with warfarin.RegistrationURL: https://www.Clinicaltrialsgov; Unique Identifier: UMIN000024006.

Project description:Background and aimsElderly patients with nonvalvular atrial fibrillation (NVAF) might have a higher risk of intracerebral hemorrhage. To investigate this, we compared the incidence of intracranial hemorrhage (ICH) 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 ischemic stroke.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 ICH. Secondary endpoints included subtypes of ICH.ResultsOf 32,275 patients (13,793 women; median age, 81.0 years) analyzed, 21,585 (66.9%) were taking DOACs and 8233 (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 ICH (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), ICH (aHR 0.68, 95% CI 0.55-0.83), and subdural/epidural hemorrhage (aHR 0.53, 95% CI 0.39-0.72) was lower in DOAC users versus warfarin users. The incidence of fatal ICH and fatal subarachnoid hemorrhage was also lower in DOAC users versus 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, (aHR 1.90, 95% CI 1.53-2.36), and long-standing persistent/permanent NVAF (aHR 1.92, 95% CI 1.60-2.30) was strongly associated with ischemic stroke; severe hepatic disease (aHR 2.67, 95% CI 1.46-4.88) was strongly associated with overall ICH; and history of fall within 1 year was strongly associated with both overall ICH (aHR 2.29, 95% CI 1.76-2.97) and subdural/epidural hemorrhage (aHR 2.90, 95% CI 1.99-4.23).ConclusionPatients aged ⩾ 75 years with NVAF taking DOACs had lower risks of ischemic stroke, ICH, 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 de-identified participant data and study protocol will be shared for up to 36 months after the 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.

Project description:BackgroundAdvancing age, decreasing renal function, and atrial fibrillation are strongly associated. Real-world evidence of direct oral anticoagulant (DOAC) use among elderly patients ≥75 years of age with nonvalvular atrial fibrillation and renal dysfunction is limited.ObjectivesThis study sought to assess 2-year outcomes and anticoagulant treatment, stratified by renal function.MethodsEnrolled patients were divided into 4 subgroups by creatinine clearance (CrCl) to determine the impact of renal dysfunction on clinical outcomes.ResultsOf 32,275 patients, 26,202 with CrCl data were analyzed (median follow-up 2.00 [IQR: 1.92-2.00] years); 1.3% of patients had CrCl <15 mL/min, 10.7% had CrCl 15 to <30 mL/min, 33.4% had CrCl 30 to <50 mL/min, 35.8% had CrCl ≥50 mL/min, and 18.9% had unknown CrCl. Cumulative incidences of stroke/systemic embolic events, major bleeding, major plus clinically relevant nonmajor bleeding, cardiovascular death, all-cause death, and net clinical outcomes increased with decreasing CrCl. In multivariable Cox regression analysis, lower CrCl emerged as an independent risk factor for these clinical outcomes, except for major bleeding, compared with CrCl ≥50 mL/min. The effectiveness and safety of DOACs over warfarin were similar or better across 3 CrCl subgroups with CrCl 15 mL/min or more. DOAC use was associated with a lower risk of stroke/systemic embolic events, major bleeding, cardiovascular death, all-cause death, and net clinical outcome compared with warfarin in patients with CrCl 30 to <50 mL/min.ConclusionsIncidences of major clinical outcomes increased with decreasing renal function in elderly nonvalvular atrial fibrillation patients. DOACs were effective and safe even in patients with renal dysfunction (CrCl 15-<50 mL/min). (Prospective Observational Study in Late-Stage Elderly Patients with Non-Valvular Atrial Fibrillation: All Nippon AF In Elderly Registry [ANAFIE Registry]; UMIN000024006).

Project description:ImportanceMany patients with nonvalvular atrial fibrillation (NVAF) are at a high risk of gastrointestinal (GI) bleeding due to conditions including older age; stage III to V chronic kidney disease (CKD); HAS-BLED (hypertension, kidney or liver disease, stroke history, prior bleeding, unstable international normalized ratio, age >65, drug or alcohol use) score of 3 or greater; corticosteroid, antiplatelet or nonsteroidal anti-inflammatory drug (NSAID) use; or GI conditions.ObjectiveTo compare the risk of stroke and/or systemic embolism (SE) and major bleeding (MB) among patients with NVAF and high risk of GI bleeding who received non-vitamin K antagonist oral anticoagulants (NOACs) vs those who received warfarin.Design, setting, and participantsThis retrospective cohort study included patients with NVAF who were 75 years and older; had stage III to V CKD; had an HAS-BLED score of 3 or greater; used corticosteroids, antiplatelets, or NSAIDs; or had GI conditions. Data were collected from the Centers for Medicare & Medicaid Services and 4 commercial insurance databases between January 1, 2012, and September 30, 2015. Data analysis was conducted from January 2012 to September 2015.ExposuresNew prescription for apixaban, dabigatran, rivaroxaban, or warfarin between January 1, 2013, and September 30, 2015 (identification period).Main outcomes and measuresSix propensity score-matched cohorts were created to compare between study drugs. For the primary objective, Cox models were used to estimate stroke and/or SE and MB hazard ratios (HRs).ResultsA total of 381 054 patients (187 489 [49.2%] women) with NVAF and at least 1 high-risk GI bleeding factor were identified (HAS-BLED score ≥3: 284 527 [74.7%]; aged ≥75 years: 252 835 [66.4%]; corticosteroid, antiplatelet, or NSAID therapy: 107 675 [28.3%]; prior GI bleeding conditions: 74 818 [19.6%]; and stage III-V CKD: 56 892 [14.9%]). All NOACs were associated with a lower risk of stroke and/or SE vs warfarin (apixaban: HR, 0.60; 95% CI, 0.52-0.68; dabigatran: HR, 0.75; 95% CI, 0.64-0.88; rivaroxaban: HR, 0.79; 95% CI, 0.73-0.86). Compared with warfarin, apixaban and dabigatran were associated with a lower risk of MB (apixaban: HR, 0.59; 95% CI, 0.56-0.63; dabigatran: HR, 0.78; 95% CI, 0.70-0.86), while rivaroxaban was associated with a higher risk (HR, 1.11; 95% CI, 1.05-1.16).Conclusions and relevanceIn this study of patients with NVAF and high risk of GI bleed, NOACs were associated with lower rates of stroke and/or SE, but NOACs had varying risks of MB compared with warfarin. These results may help inform treatment options in this patient population.