International normalized ratio stabilization in newly initiated warfarin patients with nonvalvular atrial fibrillation

Abstract

Background:

Warfarin is effective for stroke prevention in patients with atrial fibrillation (AF), but international normalized ratio (INR) levels fluctuate and frequent monitoring is necessary.

Methods:

This study used data from a large anticoagulation management service database to analyze the relationship between INR stabilization and warfarin utilization for >1 year in patients with nonvalvular AF (NVAF). Anticoagulation records from a large US electronic database collected from 2006 to 2010 were analyzed.

Results:

Patients with NVAF and ≥3 INR values in the dataset were identified (n = 15,276). INR stabilization was defined as the first three consecutive INR values between 2.0 and 3.0 after warfarin initiation. One quarter of patients (n = 3809) failed to reach INR stabilization. After initial stabilization, 30% of subsequent INR values were out of range. The mean (±standard deviation [SD]) follow-up time from stabilization to the end of study for these patients was 494.2 ± 418.1 days. Age ≥75 years (odds ratio [OR] = 1.17, 95% confidence interval [CI] = 1.08–1.27), hypertension (OR = 1.19, 95% CI = 1.10–1.29), or prior stroke (OR = 1.29, 95% CI = 1.04–1.61) were positively associated with achieving stabilization; heart failure was negatively associated with stabilization (OR = 0.78, 95% CI = 0.70–0.87). Male gender (p < 0.0001) and hypertension were associated with earlier stabilization (p = 0.0013); heart failure was associated with later stabilization (p = 0.0098). Patients who achieved INR stabilization within 1 year were 10 times more likely to remain on warfarin than patients who did not achieve it.

Limitations:

Observational data may contain incomplete records. Data on adherence, concurrent medications, vitamin K intake, genotype, reasons for discontinuation of monitoring, and patient outcomes were not available in the dataset. The study findings were generalizable only to patients with AF who were managed by anticoagulation clinics.

Conclusion:

Given the importance of stroke prevention among patients with AF, the potential for unpredictable INR patterns should be carefully considered during clinical decision-making.

Keywords::

• International normalized ratio
• Nonvalvular atrial fibrillation
• Stabilization
• Warfarin

Transparency

Declaration of funding

This study was supported by Janssen Scientific Affairs LLC, Raritan, NJ, USA.

W.W.N. and J.R.S. contributed to the study concept and design; W.W.N. and L.E.F. to the acquisition of data; W.W.N., S.D., C.V.D., L.L., P.W., and J.R.S. to the analysis and interpretation of data; and W.W.N. and S.D. to development of the first draft.

Declaration of financial/other relationships

W.W.N. and J.R.S. have disclosed that they are employees of Janssen Scientific Affairs LLC (a J&J company). S.D. has disclosed that she is a consultant of CTI/S2 Statistical Solutions and a paid consultant to Janssen Scientific Affairs. C.V.D. and L.L. have disclosed that they are employees of Janssen R&D LLC (a J&J company). L.E.F. and P.W. have disclosed that they are employees of Janssen Pharmaceuticals Inc. (a J&J company). All J&J authors are shareholders of J&J.

CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work. Peer reviewer 1 has disclosed that she has done consulting for and received grants from Janssen Pharmaceuticals. Peer reviewer 2 has no relevant financial or other relationships to disclose.

Acknowledgments

The authors would like to acknowledge Lisa Grauer MSc of Chameleon Communications International, who provided editorial support with funds provided by Janssen Scientific Affairs LLC.