M Cecilia Bahit1, Christopher B Granger2, John H Alexander2, Hillary Mulder2, Daniel M Wojdyla2, Michael Hanna3, Shinya Goto4, Denis Xavier5, Freek W A Verheugt6, Fernando Lanas7, Ziad Hijazi8, Lars Wallentin8, Renato D Lopes9. 1. INECO Neurociencias Oroño, Rosario, Santa Fe, Argentina. 2. Duke Clinical Research Institute, Durham, NC, United States of America. 3. Bristol-Myers Squibb, Princeton, NJ, United States of America. 4. Tokai University School of Medicine, Isehara, Japan. 5. St. John's Medical College, Bangalore, India. 6. Department of Cardiology, Onze Lieve Vrouwe Gasthuis (OLVG), Amsterdam, Netherlands. 7. Universidad de la Frontera, Temuco, Chile. 8. Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden. 9. Duke Clinical Research Institute, Durham, NC, United States of America. Electronic address: renato.lopes@duke.edu.
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.
RCT Entities:
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.
Authors: Tymon Pol; Ziad Hijazi; Johan Lindbäck; John H Alexander; M Cecilia Bahit; Raffaele De Caterina; J W Eikelboom; Michael D Ezekowitz; Bernard J Gersh; Christopher B Granger; Elaine M Hylek; Renato Lopes; Agneta Siegbahn; Lars Wallentin Journal: Open Heart Date: 2021-03