What is the clinical evidence from this study?

Study design: Observational. Population: Nonvalvular atrial fibrillation (n=285292). Intervention: Apixaban, dabigatran, or rivaroxaban vs. Warfarin. Primary outcome: Stroke/systemic embolism (SE) (Apixaban vs Warfarin) (HR 0.61, 95% CI 0.54-0.69).

December 1, 2018Open Access

Effectiveness and Safety of Oral Anticoagulants Among Nonvalvular Atrial Fibrillation Patients

Key Result

Apixaban (HR 0.61), dabigatran (HR 0.80), and rivaroxaban (HR 0.75) reduced the risk of stroke or systemic embolism compared to warfarin in patients with nonvalvular atrial fibrillation.

Study Design

Type

Observational (n=285,292)

Multicenter

Yes

Structured PICO

Do NOACs (apixaban, dabigatran, rivaroxaban) reduce stroke/systemic embolism and major bleeding compared to warfarin in patients with nonvalvular atrial fibrillation in real-world practice?

Population

285,292 patients with nonvalvular atrial fibrillation (NVAF) pooled from US Medicare and 4 commercial claims databases, mean age ~71-74 years, ~54-59% male. Key inclusion: ≥1 pharmacy claim for apixaban, dabigatran, rivaroxaban, or warfarin between January 1, 2013, and September 30, 2015; continuous enrollment for ≥12 months. Key exclusion: prior OAC treatment within 12 months, valvular heart disease, venous thromboembolism, transient AF, heart valve replacement/transplant, pregnancy, or recent hip/knee replacement.

Intervention

Non-vitamin K antagonist oral anticoagulants (NOACs) including apixaban, dabigatran, or rivaroxaban (standard or lower doses based on index prescription).

Comparator

Warfarin (and head-to-head comparisons between NOACs), matched 1:1 using propensity scores based on demographics, Charlson Comorbidity Index, baseline bleeding/stroke history, comorbidities, and comedications.

Outcome

Time to first stroke/systemic embolism (including ischemic stroke, hemorrhagic stroke, and systemic embolism) and time to first major bleeding (including gastrointestinal bleeding, intracranial hemorrhage, and major bleeding at other key sites).hard clinical

In a large real-world cohort of patients with nonvalvular atrial fibrillation, NOACs were associated with lower rates of stroke/systemic embolism compared to warfarin, with varying safety profiles regarding major bleeding.

Main Result

Effect estimate: HR 0.61 (95% CI 0.54-0.69)

Limitations

Retrospective observational design using healthcare claims data, subject to residual confounding.
Outcome measures based on ICD-9-CM codes without clinical adjudication.
Lack of laboratory values (e.g., INR) and clinical data (e.g., body weight, serum creatinine) to evaluate dose reduction criteria or time in therapeutic range.
Inability to measure actual drug-taking behaviors.
May not be generalizable to uninsured patients or those solely covered by other public health insurance plans.

Abstract

Background and Purpose- This ARISTOPHANES study (Anticoagulants for Reduction in Stroke: Observational Pooled Analysis on Health Outcomes and Experience of Patients) used multiple data sources to compare stroke/systemic embolism (SE) and major bleeding (MB) among a large number of nonvalvular atrial fibrillation patients on non-vitamin K antagonist oral anticoagulants (NOACs) or warfarin. Methods- A retrospective observational study of nonvalvular atrial fibrillation patients initiating apixaban, dabigatran, rivaroxaban, or warfarin from January 1, 2013, to September 30, 2015, was conducted pooling Centers for Medicare and Medicaid Services Medicare data and 4 US commercial claims databases. After 1:1 NOAC-warfarin and NOAC-NOAC propensity score matching in each database, the resulting patient records were pooled. Cox models were used to evaluate the risk of stroke/SE and MB across matched cohorts. Results- A total of 285 292 patients were included in the 6 matched cohorts: 57 929 apixaban-warfarin, 26 838 dabigatran-warfarin, 83 007 rivaroxaban-warfarin, 27 096 apixaban-dabigatran, 62 619 apixaban-rivaroxaban, and 27 538 dabigatran-rivaroxaban patient pairs. Apixaban (hazard ratio HR, 0.61; 95% CI, 0.54-0.69), dabigatran (HR, 0.80; 95% CI, 0.68-0.94), and rivaroxaban (HR, 0.75; 95% CI, 0.69-0.82) were associated with lower rates of stroke/SE compared with warfarin. Apixaban (HR, 0.58; 95% CI, 0.54-0.62) and dabigatran (HR, 0.73; 95% CI, 0.66-0.81) had lower rates of MB, and rivaroxaban (HR, 1.07; 95% CI, 1.02-1.13) had a higher rate of MB compared with warfarin. Differences exist in rates of stroke/SE and MB across NOACs. Conclusions- In this largest observational study to date on NOACs and warfarin, the NOACs had lower rates of stroke/SE and variable comparative rates of MB versus warfarin. The findings from this study may help inform the discussion on benefit and risk in the shared decision-making process for stroke prevention between healthcare providers and nonvalvular atrial fibrillation patients. Clinical Trial Registration- URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT03087487.

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