Apixaban in Comparison With Warfarin in Patients With Atrial Fibrillation and Valvular Heart Disease: Findings From the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial

doi:10.1161/CIRCULATIONAHA.114.014807

Randomized Controlled Trial

. 2015 Aug 25;132(8):624-32.

doi: 10.1161/CIRCULATIONAHA.114.014807. Epub 2015 Jun 23.

Apixaban in Comparison With Warfarin in Patients With Atrial Fibrillation and Valvular Heart Disease: Findings From the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial

Alvaro Avezum¹, Renato D Lopes², Phillip J Schulte², Fernando Lanas², Bernard J Gersh², Michael Hanna², Prem Pais², Cetin Erol², Rafael Diaz², M Cecilia Bahit², Jozef Bartunek², Raffaele De Caterina², Shinya Goto², Witold Ruzyllo², Jun Zhu², Christopher B Granger², John H Alexander²

Affiliations

¹ From Research Division, Dante Pazzanese Institute of Cardiology, São Paulo, Brazil (A.A.); Duke Clinical Research Institute, Duke Medicine, Durham, NC (R.D.L., P.J.S., C.B.G., J.H.A.); Universidad de La Frontera, Temuco, Chile (F.L.); Mayo Clinic College of Medicine, Rochester, MN (B.J.G.); Bristol-Myers Squibb, Princeton, NJ (M.H.); St. John's Medical College & Research Institute, Bangalore, India (P.P.); Ankara University School of Medicine, Turkey (C.E.); ECLA Estudios Cardiológicos Latinoamérica, Rosario, Argentina (R.D.); INECO Neurociencias Oroño, Rosario, Santa Fe, Argentina (M.C.B.); Cardiovascular Center Aalst, OLV Hospital, Aalst, Belgium (J.B.); G. d'Annunzio University, Chieti, Italy and Fondazione Toscana G. Monasterio, Pisa, Italy (R.D.C.); Tokai University School of Medicine, Isehara, Japan (S.G.); National Institute of Cardiology, Warsaw, Poland (W.R.); and Fu Wai Hospital, Beijing, China (J.Z.). avezum@dantepazzanese.org.br.
² From Research Division, Dante Pazzanese Institute of Cardiology, São Paulo, Brazil (A.A.); Duke Clinical Research Institute, Duke Medicine, Durham, NC (R.D.L., P.J.S., C.B.G., J.H.A.); Universidad de La Frontera, Temuco, Chile (F.L.); Mayo Clinic College of Medicine, Rochester, MN (B.J.G.); Bristol-Myers Squibb, Princeton, NJ (M.H.); St. John's Medical College & Research Institute, Bangalore, India (P.P.); Ankara University School of Medicine, Turkey (C.E.); ECLA Estudios Cardiológicos Latinoamérica, Rosario, Argentina (R.D.); INECO Neurociencias Oroño, Rosario, Santa Fe, Argentina (M.C.B.); Cardiovascular Center Aalst, OLV Hospital, Aalst, Belgium (J.B.); G. d'Annunzio University, Chieti, Italy and Fondazione Toscana G. Monasterio, Pisa, Italy (R.D.C.); Tokai University School of Medicine, Isehara, Japan (S.G.); National Institute of Cardiology, Warsaw, Poland (W.R.); and Fu Wai Hospital, Beijing, China (J.Z.).

PMID: 26106009
DOI: 10.1161/CIRCULATIONAHA.114.014807

Randomized Controlled Trial

Apixaban in Comparison With Warfarin in Patients With Atrial Fibrillation and Valvular Heart Disease: Findings From the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial

Alvaro Avezum et al. Circulation. 2015.

. 2015 Aug 25;132(8):624-32.

doi: 10.1161/CIRCULATIONAHA.114.014807. Epub 2015 Jun 23.

Authors

Affiliations

¹ From Research Division, Dante Pazzanese Institute of Cardiology, São Paulo, Brazil (A.A.); Duke Clinical Research Institute, Duke Medicine, Durham, NC (R.D.L., P.J.S., C.B.G., J.H.A.); Universidad de La Frontera, Temuco, Chile (F.L.); Mayo Clinic College of Medicine, Rochester, MN (B.J.G.); Bristol-Myers Squibb, Princeton, NJ (M.H.); St. John's Medical College & Research Institute, Bangalore, India (P.P.); Ankara University School of Medicine, Turkey (C.E.); ECLA Estudios Cardiológicos Latinoamérica, Rosario, Argentina (R.D.); INECO Neurociencias Oroño, Rosario, Santa Fe, Argentina (M.C.B.); Cardiovascular Center Aalst, OLV Hospital, Aalst, Belgium (J.B.); G. d'Annunzio University, Chieti, Italy and Fondazione Toscana G. Monasterio, Pisa, Italy (R.D.C.); Tokai University School of Medicine, Isehara, Japan (S.G.); National Institute of Cardiology, Warsaw, Poland (W.R.); and Fu Wai Hospital, Beijing, China (J.Z.). avezum@dantepazzanese.org.br.
² From Research Division, Dante Pazzanese Institute of Cardiology, São Paulo, Brazil (A.A.); Duke Clinical Research Institute, Duke Medicine, Durham, NC (R.D.L., P.J.S., C.B.G., J.H.A.); Universidad de La Frontera, Temuco, Chile (F.L.); Mayo Clinic College of Medicine, Rochester, MN (B.J.G.); Bristol-Myers Squibb, Princeton, NJ (M.H.); St. John's Medical College & Research Institute, Bangalore, India (P.P.); Ankara University School of Medicine, Turkey (C.E.); ECLA Estudios Cardiológicos Latinoamérica, Rosario, Argentina (R.D.); INECO Neurociencias Oroño, Rosario, Santa Fe, Argentina (M.C.B.); Cardiovascular Center Aalst, OLV Hospital, Aalst, Belgium (J.B.); G. d'Annunzio University, Chieti, Italy and Fondazione Toscana G. Monasterio, Pisa, Italy (R.D.C.); Tokai University School of Medicine, Isehara, Japan (S.G.); National Institute of Cardiology, Warsaw, Poland (W.R.); and Fu Wai Hospital, Beijing, China (J.Z.).

PMID: 26106009
DOI: 10.1161/CIRCULATIONAHA.114.014807

Abstract

Background: Apixaban is approved for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. However, the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial included a substantial number of patients with valvular heart disease and only excluded patients with clinically significant mitral stenosis or mechanical prosthetic heart valves.

Methods and results: We compared the effect of apixaban and warfarin on rates of stroke or systemic embolism, major bleeding, and death in patients with and without moderate or severe valvular heart disease using Cox proportional hazards modeling. Of the 18 201 patients enrolled in ARISTOTLE, 4808 (26.4%) had a history of moderate or severe valvular heart disease or previous valve surgery. Patients with valvular heart disease had higher rates of stroke or systemic embolism and bleeding than patients without valvular heart disease. There was no evidence of a differential effect of apixaban over warfarin in patients with and without valvular heart disease in reducing stroke and systemic embolism (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.51-0.97 and HR, 0.84; 95%, CI 0.67-1.04; interaction P=0.38), causing less major bleeding (HR, 0.79; 95% CI, 0.61-1.04 and HR, 0.65; 95% CI, 0.55-0.77; interaction P=0.23), and reducing mortality (HR, 1.01; 95% CI, 0.84-1.22 and HR, 0.84; 95% CI, 0.73-0.96; interaction P=0.10).

Conclusions: More than a quarter of the patients in ARISTOTLE with nonvalvular atrial fibrillation had moderate or severe valvular heart disease. There was no evidence of a differential effect of apixaban over warfarin in reducing stroke or systemic embolism, causing less bleeding, and reducing death in patients with and without valvular heart disease.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984.

Keywords: apixaban; atrial fibrillation; heart diseases; hemorrhage; oral anticoagulant; stroke; valvular heart disease.

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Apixaban in Comparison With Warfarin in Patients With Atrial Fibrillation and Valvular Heart Disease: Findings From the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial

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Apixaban in Comparison With Warfarin in Patients With Atrial Fibrillation and Valvular Heart Disease: Findings From the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial

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