Regional variation in clinical characteristics and outcomes in patients with atrial fibrillation: Findings from the ARISTOTLE trial

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Highlights

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    In patients with AF, there are differences in patient characteristics and practice patterns by region.

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    Patients in the Asia Pacific region had worse outcomes than patients in other regions.

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    There is an even greater benefit of less bleeding with apixaban than warfarin in patients from Asia Pacific.

Abstract

Background

Variation in patient characteristics and practice patterns may influence outcomes at a regional level.

Methods

We assessed differences in demographics, practice patterns, outcomes, and the effect of apixaban compared with warfarin in ARISTOTLE (n = 18,201) by prespecified regions: North America, Latin America, Europe, and Asia Pacific. The primary outcomes were stroke/systemic embolism and major bleeding.

Results

Compared with other regions, patients from Asia Pacific were younger, more women were enrolled in Latin America. Coronary artery disease was more prevalent in Europe and Asia Pacific had the highest rate of prior stroke and renal impairment. Over 50% of patients in North America were taking ≥9 drugs at randomization, compared with 10% in Latin America. North America had the highest rates of temporary study drug discontinuation and procedures. Time in therapeutic range (INR 2.0–3.0) on warfarin was highest in North America and lowest in Asia Pacific. After adjustment and compared with Europe, patients in Asia Pacific had 2-fold higher risk of stroke/systemic embolism and 3-fold higher risk of intracranial hemorrhage. Patients in Latin America had 2-fold increased risk of all-cause death compared with Europe. The benefits of apixaban compared with warfarin were consistent across regions; there was a pronounced reduction in major bleeding in patients from Asia Pacific compared with other regions (p-interaction = 0.03).

Conclusions

Patients with AF enrolled in prespecified regions in ARISTOTLE had differences in clinical baseline characteristics and practice patterns. After adjustment, patients in Asia Pacific and Latin America had worse outcomes than patients from other regions. The relative benefits of apixaban compared with warfarin were consistent across regions with an even greater treatment effect in the reduction of bleeding in patients from Asia Pacific.

Introduction

Atrial fibrillation (AF) is the most common sustained arrhythmia in the world and is associated with an increased risk of stroke and mortality [1]. There is evidence of progressive increases in overall burden, incidence, prevalence, and AF-associated mortality, with significant public health implications [2]. Significant variations in clinical characteristics and patterns of care in different regions of the world have been described. Since differences in patient characteristics and clinical management may influence outcomes at a regional level, we decided to assess the regional variation in the international multicenter ARISTOTLE trial [3,4], which included 18,201 patients with AF from 37 countries. We aimed to describe differences in demographic, clinical characteristics, and practice patterns by region of the world, categorized as North America, Latin America, Europe, and Asia Pacific and sought to determine if there were differences in clinical outcomes by region.

Section snippets

Methods

The design and results of the ARISTOTLE trial have been published previously [3,4]. Patients were randomly assigned to receive treatment with either apixaban 5 mg twice daily or warfarin (target international normalized ratio 2.0–3.0 [median time in therapeutic range (TTR) of 66%]) for a median of 1.8 years. A reduced dose of apixaban 2.5 mg twice daily was used for patients who met ≥2 of the following dose-reduction criteria: age ≥ 80 years, body weight ≤ 60 kg, or creatinine ≥1.5 mg/dL.

Results

Definition of geographical regions and patient enrollment in the ARISTOTLE study are shown in Fig. 1. Baseline characteristics of the 18,201 patients enrolled in ARISTOTLE are presented according to region in Table 1. The most prevalent comorbidities were hypertension (varying from 89.5% in Europe to 80.6% in Asia Pacific) and diabetes (varying from 31.8% in North America to 20.2% in Latin America). The mean CHADS2 score was highest in Europe (2.2) and similar in the rest of the regions (2.1)

Discussion

We found that patients from the ARISTOTLE trial differed according to major world regions with respect to baseline characteristics and practice patterns, and that even after adjustment for clinical factors and biomarkers, patients from the Asia Pacific region and Latin America had worse outcomes. Interestingly, for safety outcomes including intracranial hemorrhage, patients from Asia Pacific as compared with those from other regions seemed to benefit most from apixaban compared with warfarin.

Funding source

The ARISTOTLE trial was funded by Bristol-Myers Squibb, Co., Princeton, NJ, USA and Pfizer Inc., New York, NY, USA.

Disclosures

Bahit: Educational grant from Boehringer Ingelheim; honoraria from Merck & Co (for role as national coordinator). Granger: Consulting fees/Honoraria: AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, Gilead Sciences, Inc., GlaxoSmithKline, Hoffman LaRoche, Janssen, Medtronic Inc., Novartis, Pfizer, The Medicines Company, Verseon; Research grants: Armetheon, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi,

CRediT authorship contribution statement

M. Cecilia Bahit: Conceptualization, Data curation, Investigation, Writing - original draft. Christopher B. Granger: Data curation, Investigation, Writing - review & editing, Supervision. John H. Alexander: Data curation, Investigation, Writing - review & editing, Supervision. Hillary Mulder: Methodology, Software, Formal analysis, Writing - review & editing. Daniel M. Wojdyla: Methodology, Software, Formal analysis, Writing - review & editing. Michael Hanna: Data curation, Writing - review &

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Employee of Bristol-Myers Squibb during trial conduct.

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© 2019 Published by Elsevier B.V.