Time in therapeutic range inwarfarin-treated patients is very good good enough?

Rod Passman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

118 Scopus citations


IMPORTANCE Vitamin K antagonist (eg, warfarin) use is nowadays challenged by the non-Vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in atrial fibrillation (AF). NOAC studies were based on comparisons with warfarin arms with times in therapeutic range (TTRs) of 55.2%to 64.9%, making the results less credible in health care systems with higher TTRs. OBJECTIVES To evaluate the efficacy and safety of well-managed warfarin therapy in patients with nonvalvular AF, the risk of complications, especially intracranial bleeding, in patients with concomitant use of aspirin, and the impact of international normalized ratio (INR) control. DESIGN, SETTING, AND PARTICIPANTS A retrospective, multicenter cohort study based on Swedish registries, especially AuriculA, a quality register for AF and oral anticoagulation, was conducted. The register contains nationwide data, including that from specialized anticoagulation clinics and primary health care centers. A total of 40 449 patients starting warfarin therapy owing to nonvalvular AF during the study period were monitored until treatment cessation, death, or the end of the study. The study was conducted from January 1, 2006, to December 31, 2011, and data were analyzed between February 1 and November 15, 2015. Associating complications with risk factors and individual INR control, we evaluated the efficacy and safety of warfarin treatment in patients with concomitant aspirin therapy and those with no additional antiplatelet medications. EXPOSURES Use of warfarin with and without concomitant therapy with aspirin. MAIN OUTCOMES AND MEASURES Annual incidence of complications in association with individual TTR (iTTR), INR variability, and aspirin use and identification of factors indicating the probability of intracranial bleeding. RESULTS Of the 40 449 patients included in the study, 16 201 (40.0%)werewomen; mean (SD) age of the cohortwas 72.5 (10.1) years, and the mean CHA2DS2-VASc (cardiac failure or dysfunction, hypertension, age ≥75 years [doubled], diabetes mellitus, stroke [doubled]-vascular disease, age 65-74 years, and sex category [female]) scorewas 3.3 at baseline. The annual incidence, reported as percentage (95%CI) of all-cause mortalitywas 2.19% (2.07-2.31) and, for intracranial bleeding, 0.44%(0.39-0.49). Patients receiving concomitant aspirin had annual rates of any major bleeding of 3.07%(2.70-3.44) and thromboembolism of 4.90%(4.43-5.37), and those with renal failurewere at higher risk of intracranial bleeding (hazard ratio, 2.25; 95%CI, 1.32-3.82). Annual rates of any major bleeding and any thromboembolism in iTTR less than 70%were 3.81% (3.51-4.11) and 4.41%(4.09-4.73), respectively, and, in high INR variability,were 3.04%(2.85-3.24) and 3.48%(3.27-3.69), respectively. For patients with iTTR 70%or greater, the level of INR variability did not alter event rates. CONCLUSIONS AND RELEVANCEWell-managedwarfarin therapy is associated with a low risk of complications and is still a valid alternative for prophylaxis of AF-associated stroke. Therapy should be closely monitored for patients with renal failure, concomitant aspirin use, and poor INR control.

Original languageEnglish (US)
Pages (from-to)872-873
Number of pages2
JournalJAMA - Journal of the American Medical Association
Issue number8
StatePublished - Aug 23 2016

ASJC Scopus subject areas

  • General Medicine


Dive into the research topics of 'Time in therapeutic range inwarfarin-treated patients is very good good enough?'. Together they form a unique fingerprint.

Cite this