Prof. Lars Wallentin,
Dr. Jean-Philippe Collet ,
Presenter | see Discussant report
Lars Wallentin (Sweden)Presentation webcastPresentation slides
List of Authors: Lars Wallentin, Renato D. Lopes, Michael Hanna, Hussein R. Al-Khalidi, Sunil Nepal, Elaine M. Hylek, Sana M. Al-Khatib, John H. Alexander, Marco Alings, John Amerena, Jack Ansell, Philip Aylward, Jozef Bartunek, Patrick Commerford, Raffaele De Caterina, Cetin Erol, Veli Pekka Harjola, Claes Held, John Horowitz, Kurt Huber, Steen Husted, Matyas Keltai, Fernando Lanas, Liu Lisheng, John J. V. McMurray, Byung-Hee Oh, Mårten Rosenqvist, Witold Ruzyllo, Philippe Gabriel Steg, Dragos Vinereanu, Denis Xavier, and Christopher B. Granger, on behalf of the ARISTOTLE Investigators.
Background: Efficacy and safety of warfarin for stroke prevention in patients with atrial fibrillation are related to time in therapeutic range (TTR) with International Normalized Ratio (INR) between 2.0 and 3.0. The ARISTOTLE trial showed that, compared with warfarin, apixaban reduced stroke and systemic embolism, major bleeding, and mortality. We analyzed these treatment effects in relation to centres’ quality of INR control. Methods: The trial randomized 18,201 patients in 1034 centres in 39 countries to double blind, doubledummy treatment with apixaban 5 mg twice daily versus warfarin. INR was monitored at least monthly by an encrypted point-of-care device to maintain the double blind. Each centre’s TTR was calculated as the median of all individuals’ TTRs in the warfarin treated patients by the Rosendaal method. The treatments’ effects on outcomes were compared across quartiles of centres’ TTR with tests of interaction adjusted for differences in baseline characteristics. Results: Median for centres’ TTR was 65.7% (interquartile limits 58.0% and 72.2%). Across centres’ TTR quartiles there were consistently lower rates of stroke and systemic embolism and major bleeding with apixaban than warfarin. In the lowest and highest centres’ TTR quartiles, hazard ratios (HR) were respectively 0.77 (95%CI 0.56 – 1.06) and 0.81 (95%CI 0.52 - 1.26) for stroke or systemic embolism and 0.53 (95%CI 0.39 - 0.72) and 0.72 (95%CI 0.55 - 0.93) for major bleeding. Conclusion: The benefits of apixaban compared with warfarin in preventing stroke or systemic embolism and for causing less bleeding are consistent irrespective of centres’ quality of INR control.
Discussant | see Presenter abstract
Jean-Philippe Collet (France)
Most important findings:
The benefit of apixaban over warfarin was observed irrespective of the level of INR and therefore is not affected by local standard of care. Strengths:
Implementation issues: Would anti-Xa measurements in addition to TTR help to better discriminate who would benefit from apixaban over warfarin in low TTR center?
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Clinical Trial Update I - Drug treatment
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