Warfarin treatment in patients with atrial fibrillation: Observing outcomes associated with varying levels of INR control

doi:10.1016/j.thromres.2008.09.016

Thrombosis Research

Volume 124, Issue 1, May 2009, Pages 37-41

https://doi.org/10.1016/j.thromres.2008.09.016 Get rights and content

Abstract

Introduction

We aimed to determine the level of INR control associated with reduced stroke and mortality.

Material and methods

The study used a retrospective cohort design using linked inpatient, haematology and mortality data from Cardiff and the Vale of Glamorgan, UK.

Anonymised patients admitted with a diagnosis of non-valvular atrial fibrillation (NVAF) were defined as warfarin or non-warfarin treated by number of repeated International Normalised Ratio (INR) tests. Warfarin treated patients (> 5 INR tests) categorised as at moderate or high risk of stroke (CHADS₂ score ≥ 2) with varying levels of INR control were compared to those who did not receive warfarin treatment using Cox proportional hazards models controlling for age, sex and CHADS₂ score. Outcome measures were time to stroke and mortality.

Results

6,108 patients with NVAF were identified. 2,235 (36.6%) of these patients had five or more INR readings and of these 486 (21.7%) had CHADS₂ score ≥ 2. There was significant improvement in time to stroke event in those patients with INR control of greater than 70% of time in therapeutic range (2.0 to 3.0) compared with the non-warfarin treatment group. Overall survival was significantly improved for all warfarin treated groups with INR control of greater than 40% of time in range.

Conclusions

Patients with INR control of above 70% of time in range had a significantly reduced risk of stroke. Patient suitability for warfarin treatment should be continuously assessed based on their ability to maintain a consistently therapeutic INR.

Section snippets

Intoduction

Recent studies in the US and Europe have reported a prevalence of non-valvular atrial fibrillation (NVAF) of approximately 1% [1], [2]. There is a strong age relationship with prevalence in those aged over 85 years of age in excess of 10% [1], [3] and a secular trend of increasing incidence [1], [2], [4].

The risk of stroke has been shown to be five times greater in patients with NVAF than those without [5]. To counter this, the use of long-term oral anticoagulation with a vitamin K antagonist

Patients and setting

The study was conducted in Cardiff and the Vale of Glamorgan, United Kingdom (population = 434,000) using routine data collated between April 1995 and March 2000. In particular three datasets were used. The first was routine hospital inpatient data from April 1995 to March 2000 containing a range of information including up to six diagnostic codes, length of stay and destination on discharge. The second was a haematology laboratory dataset reporting from June 1995 to January 2002 and containing

Results

A total of 222,398 patients were hospitalised during the study period of whom 6,245 (2.8%) were adults with a diagnosis of NVAF. After the exclusion of 139 patients (2.2%) with a history of heart valve surgery there remained 6,106 (97.8%); of these 2,235 (36.6%) had a minimum of 5 INR readings and of these 486 (21.7%) had a CHADS₂ score ≥ 2 and hence constituted the warfarin treatment group. There were 3,278 patients in the non-warfarin treatment group of whom 698 (21.3%) had a CHADS₂ score ≥ 2.

Discussion

Previous studies have reported that poor INR control was predictive of significantly worse outcomes in NVAF patients treated with warfarin [9]. In this study we sought to define what constituted good control.

After controlling for demographic and morbidity related confounders, multivariate survival analysis demonstrated only those patients a with CHADS₂ score ≥ 2 with INR control greater than 40% of time within therapeutic INR range demonstrated a significant improvement in survival. Only those

Conclusion

This paper suggests that only moderate or high risk patients with NVAF eligible for oral anticoagulation, treated with warfarin and achieving an INR control of greater than 70% of time within therapeutic range have significantly improved outcomes in terms of stroke; and only those with control in excess of over 40% have significantly improved outcomes in terms of overall mortality compared to treatment without warfarin. Poorly controlled warfarin therapy is potentially harmful and if good

Conflict of interest

Jonathan Plumb, Andreas Clemens and Paul Robinson are employed by Boehringer Ingelheim which has a new oral anticoagulant currently under investigation for stroke prevention in atrial fibrillation patients. Christopher Morgan, Phil McEwan and Andrzej Tukiendorf are employed by Cardiff Research Consortium, an independent research company commissioned by Boehringer Ingelheim to perform this study.

Acknowledgements

This study was funded by Boehringer Ingelheim International GmbH.

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Regular ArticleWarfarin treatment in patients with atrial fibrillation: Observing outcomes associated with varying levels of INR control

Abstract

Introduction

Material and methods

Results

Conclusions

Section snippets

Intoduction

Patients and setting

Results

Discussion

Conclusion

Conflict of interest

Acknowledgements

American Heart Journal

J Am Coll Cardiol

Prevalence of diagnosed atrial fibrillation in adults. National implications for rhythm management and stroke prevention: the anticoagulation and risk factors study in atrial fibrillation. (ATRIA) Study

Clin Cardiol

Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study

Eur Heart J

Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence

Circulation

Atrial fibrillation as an independent risk factor for stroke: The Framingham Study

Stroke

Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation

Ann Intern Med

Quality of anticoagulation control and costs of monitoring warfarin therapy among patients with atrial Fibrillation in Clinic Settings: A Multi-Site Managed-Care Study

Ann Pharmacother

Circulation

Anticoagulation in patients with non-valvular atrial fibrillation: an evaluation of stability and early factors that predict longer-term stability on warfarin in a large UK population

Curr Med Res Opin

Regular Article
Warfarin treatment in patients with atrial fibrillation: Observing outcomes associated with varying levels of INR control