Open AccessRelationship Between Time in Therapeutic Range and Comparative Treatment Effect of Rivaroxaban and Warfarin: Results From the ROCKET AF Trial
Author(s) -
Piccini Jonathan P.,
Hellkamp Anne S.,
Lokhnygina Yuliya,
Patel Manesh R.,
Harrell Frank E.,
Singer Daniel E.,
Becker Richard C.,
Breithardt Günter,
Halperin Jonathan L.,
Hankey Graeme J.,
Berkowitz Scott D.,
Nessel Christopher C.,
Mahaffey Kenneth W.,
Fox Keith A. A.,
Califf Robert M.
Publication year - 2014
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.113.000521
Subject(s) - rivaroxaban , medicine , warfarin , stroke (engine) , quartile , hazard ratio , clinical endpoint , atrial fibrillation , embolism , randomized controlled trial , pulmonary embolism , anesthesia , cardiology , confidence interval , mechanical engineering , engineering
Background Time in therapeutic range ( TTR ) is a standard quality measure of the use of warfarin. We assessed the relative effects of rivaroxaban versus warfarin at the level of trial center TTR (c TTR ) since such analysis preserves randomized comparisons. Methods and Results TTR was calculated using the Rosendaal method, without exclusion of international normalized ratio ( INR ) values performed during warfarin initiation. Measurements during warfarin interruptions >7 days were excluded. INR s were performed via standardized finger‐stick point‐of‐care devices at least every 4 weeks. The primary efficacy endpoint (stroke or non‐central nervous system embolism) was examined by quartiles of c TTR and by c TTR as a continuous function. Centers with the highest c TTR s by quartile had lower‐risk patients as reflected by lower CHADS 2 scores ( P <0.0001) and a lower prevalence of prior stroke or transient ischemic attack ( P <0.0001). Sites with higher c TTR were predominantly from North America and Western Europe. The treatment effect of rivaroxaban versus warfarin on the primary endpoint was consistent across a wide range of c TTR s ( P value for interaction=0.71). The hazard of major and non‐major clinically relevant bleeding increased with c TTR ( P for interaction=0.001), however, the estimated reduction by rivaroxaban compared with warfarin in the hazard of intracranial hemorrhage was preserved across a wide range of threshold c TTR values. Conclusions The treatment effect of rivaroxaban compared with warfarin for the prevention of stroke and systemic embolism is consistent regardless of c TTR .