Clinical Outcomes and History of Fall in Patients with Atrial Fibrillation Treated with Oral Anticoagulation: Insights From the ARISTOTLE Trial - 21/12/17

Doi : 10.1016/j.amjmed.2017.10.036

Meena P. Rao, MD, MPH ^a, Dragos Vinereanu, MD, PhD ^b,^* , Daniel M. Wojdyla, MS ^c, John H. Alexander, MD, MHS ^c, Dan Atar, MD, PhD ^d, Elaine M. Hylek, MD, MPH ^e, Michael Hanna, MD ^f, Lars Wallentin, MD, PhD ^g, Renato D. Lopes, MD, PhD, MHS ^c, Bernard J. Gersh, MB, ChB, DPhil ^h, Christopher B. Granger, MD ^c
on behalf of the
Apixaban for Reduction in Stroke Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Investigators
^a Cape Fear Heart Associates, New Hanover Regional Medical Center, Wilmington, NC
^b University of Medicine and Pharmacy Carol Davila, University and Emergency Hospital of Bucharest, Romania
^c Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC
^d University of Oslo, Norway
^e Boston University School of Medicine, Mass
^f Bristol-Myers Squibb, Princeton, NJ
^g Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
^h Mayo Clinic College of Medicine, Rochester, Minn

^*Requests for reprints should be addressed to Dragos Vinereanu, MD, PhD, FRCP, Department of Cardiology, University and Emergency Hospital of Bucharest, 169 Splaiul Independentei, Sector 5, Bucharest 050098, Romania.Department of CardiologyUniversity and Emergency Hospital of Bucharest169 Splaiul Independentei, Sector 5Bucharest050098Romania

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Thursday 21 December 2017

Abstract

Purpose

We assessed outcomes among anticoagulated patients with atrial fibrillation and a history of falling, and whether the benefits of apixaban vs warfarin are consistent in this population.

Methods

Of the 18,201 patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) study, 16,491 had information about history of falling–753 with history of falling and 15,738 without history of falling. The primary efficacy outcome was stroke or systemic embolism; the primary safety outcome was major bleeding.

Results

When compared with patients without a history of falling, patients with a history of falling were older, more likely to be female and to have dementia, cerebrovascular disease, depression, diabetes, heart failure, osteoporosis, fractures, and higher CHA₂DS₂-VASc (Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, prior Stroke or TIA or thromboembolism, Vascular disease, Age 65-74 years, Sex category female) and HAS-BLED (Hypertension, Abnormal renal and liver function, Stroke, Bleeding, Labile international normalized ratio, Elderly, Drugs or alcohol) scores. Patients with a history of falling had higher rates of major bleeding (adjusted hazard ratio [HR] 1.39; 95% confidence interval [CI], 1.05-1.84; P = .020), including intracranial bleeding (adjusted HR 1.87; 95% CI, 1.02-3.43; P = .044) and death (adjusted HR 1.70; 95% CI, 1.36-2.14; P < .0001), but similar rates of stroke or systemic embolism and hemorrhagic stroke. There was no evidence of a differential effect of apixaban compared with warfarin on any outcome, regardless of history of falling. Among those with a history of falling, subdural bleeding occurred in 5 of 367 patients treated with warfarin and 0 of 386 treated with apixaban.

Conclusions

Patients with atrial fibrillation and a history of falling receiving anticoagulation have a higher risk of major bleeding, including intracranial, and death. The efficacy and safety of apixaban compared with warfarin were consistent, irrespective of history of falling.

Le texte complet de cet article est disponible en PDF.

Keywords : Anticoagulation, Apixaban, Atrial fibrillation, Bleeding, History of falls, Stroke, Warfarin

Plan

Baseline Characteristics

Outcomes

Treatment Effect of Apixaban vs Warfarin

Discussion

Study Limitations

Conclusion

	Clinical Trial Registration: ClinicalTrials.gov: NCT00412984.
	Funding: This study was sponsored by Bristol-Myers Squibb and Pfizer. All analyses were conducted at the Duke Clinical Research Institute (Durham, NC), and the authors had full access to all data. The Duke Clinical Research Institute coordinated the trial and managed the database. An academic steering committee designed the trial and was responsible for oversight of study conduct and reporting of all results and takes responsibility for the accuracy and completeness of data analyses. The authors are fully responsible for the study design, data collection, analysis and interpretation of the data, and writing of the manuscript. The sponsor played no role in the decision to submit the manuscript for publication.
	Conflicts of Interests: MPR, DMW: None. DV: Research grants and speaker fees from Bristol-Myers Squibb, Pfizer, Boehringer Ingelheim, Bayer. JHA: Research grants from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, CryoLife, CSL Behring, Food and Drug Administration, National Institutes of Health, Sanofi, and Tenax Therapeutics. Consulting fees/honoraria from Cempra, CryoLife, CSL Behring, Duke Private Diagnostic Clinic, Merck, Pfizer, Portola Pharmaceuticals, VA Cooperative Studies Program, VasoPrep Surgical, and Zafgen. DA: Consulting fees/honoraria from Bayer HealthCare Pharmaceuticals, Sanofi, AstraZeneca Pharmaceuticals LP, BMS/Pfizer, Boehringer Ingelheim, Merck/MSD. EMH: Consulting/advisory board for Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Armetheon, Daiichi Sankyo, Janssen, Medtronic, Pfizer, Portola. MH: Employee of Bristol-Myers Squibb during the ARISTOTLE trial. LW: Research grants from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, GlaxoSmithKline, Merck/Schering-Plough, Roche Diagnostics; Consulting fees/Honoraria from Abbott, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, GlaxoSmithKline. RDL: Research grants from Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer; Consulting fees/Honoraria from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Medtronic, Merck & Co., Pfizer, Portola. BJG: Consultant/advisory board for Medtronic, Janssen Scientific Affairs, and Janssen Research & Development. CBG: Institutional research grants from Armetheon, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, US Food and Drug Administration, GlaxoSmithKline, Janssen Pharmaceuticals, The Medicines Company, Medtronic Foundation, Novartis, Pfizer, Sanofi Aventis, and Takeda.
	Consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Daiichi Sankyo, Gilead, GlaxoSmithKline, Merck, Janssen Pharmaceuticals, Medtronic, National Institutes of Health, Novartis, Pfizer, Sanofi Aventis, and Takeda.