Most patients taking warfarin long-term do not maintain stable INR values

In a study appearing in the August 9 issue of JAMA, Sean D. Pokorney, M.D., M.B.A., Eric D. Peterson, M.D., M.P.H., of Duke University Medical Center, Durham, N.C., and colleagues examined whether patients receiving warfarin who have stable international normalized ratio (INR) values remain stable over time.

Warfarin substantially decreases stroke risk among patients with atrial fibrillation yet has a narrow therapeutic window (INR values of 2.0-3.0) and is associated with multiple drug and food interactions. Non-vitamin K oral anticoagulants do not require drug monitoring and have similar or improved safety and efficacy relative to warfarin but are more costly. Whether patients previously stable on warfarin should be switched to non-vitamin K oral anticoagulants remains controversial.

Data for this study were obtained from a prospective registry of patients with atrial fibrillation from 176 clinics who were enrolled June 2010 through August 2011 and followed up for 3 years through November 2014. Patients receiving warfarin at study entry with 3 or more INR values in the first 6 months and 6 or more in the subsequent year were included. Stability was defined as 80 percent or more INRs in therapeutic range (2.0-3.0).

Of 10,132 registry patients, 6,383 were not taking warfarin or had insufficient INR values and were excluded. Among 3,749 patients taking warfarin (average age, 75 years), 968 (26 percent) had 80 percent or more of INR values in 2.0-3.0 range during the first 6 months. Of patients with stable INRs during the first 6 months, 34 percent remained stable over the subsequent year. Stability during the baseline period had limited predictive ability of stability over the subsequent year. Among patients with 80 percent or more INRs in range at baseline, 36 percent had 1 or more well-out-of-range INR in the following year, demonstrating limited predictive ability of stability on well-out-of-range INRs.

"A common belief has been that patients with stable INRs while taking warfarin would continue to be stable and derive less benefit from switching to non-vitamin K oral anticoagulants. This analysis suggests warfarin stability is difficult to predict and challenges the notion that patients who have done well taking warfarin should maintain taking warfarin," the authors write.