Relationship between time in therapeutic range and comparative treatment effect of rivaroxaban and warfarin: results from the ROCKET AF trial.

Published online

Journal Article

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 (cTTR) 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. INRs 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 cTTR and by cTTR as a continuous function. Centers with the highest cTTRs by quartile had lower-risk patients as reflected by lower CHADS2 scores (P<0.0001) and a lower prevalence of prior stroke or transient ischemic attack (P<0.0001). Sites with higher cTTR 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 cTTRs (P value for interaction=0.71). The hazard of major and non-major clinically relevant bleeding increased with cTTR (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 cTTR values. CONCLUSIONS: The treatment effect of rivaroxaban compared with warfarin for the prevention of stroke and systemic embolism is consistent regardless of cTTR.

Full Text

Duke Authors

Cited Authors

  • Piccini, JP; Hellkamp, AS; Lokhnygina, Y; Patel, MR; Harrell, FE; Singer, DE; Becker, RC; Breithardt, G; Halperin, JL; Hankey, GJ; Berkowitz, SD; Nessel, CC; Mahaffey, KW; Fox, KAA; Califf, RM; ROCKET AF Investigators,

Published Date

  • April 22, 2014

Published In

Volume / Issue

  • 3 / 2

Start / End Page

  • e000521 -

PubMed ID

  • 24755148

Pubmed Central ID

  • 24755148

Electronic International Standard Serial Number (EISSN)

  • 2047-9980

Digital Object Identifier (DOI)

  • 10.1161/JAHA.113.000521

Language

  • eng

Conference Location

  • England