Elsevier

Clinical Therapeutics

Volume 34, Issue 7, July 2012, Pages 1511-1520
Clinical Therapeutics

Pharmacotherapy
Original research
Identifying Potential Predictors of High-Quality Oral Anticoagulation Assessed by Time in Therapeutic International Normalized Ratio Range: A Prospective, Long-Term, Single-Center, Observational Study

https://doi.org/10.1016/j.clinthera.2012.06.002Get rights and content

Abstract

Background

The efficacy and risks of oral anticoagulation are largely associated with maintaining the quality of anticoagulation control. Nevertheless, few studies have addressed which factors, if any, are associated with this control.

Objective

This study aimed to identify predictors of high-quality oral anticoagulation.

Methods

A prospective observational study enrolled all adult patients on intended long-term oral anticoagulation attending a public anticoagulation clinic. Patients with high-quality anticoagulation, defined as percentage of time in therapeutic international normalized ratio (INR) range (TTR) ≥66%, were compared with those with poor anticoagulation control (TTR <66%). Measures included cognitive, psychological, and relevant behavioral factors, in addition to traditionally implicated ones, such as age, comorbidity, and concurrent medications.

Results

Participation was requested from all 233 patients followed up at the anticoagulation clinic. Eighty-six did not meet the inclusion criteria (49 due to intended anticoagulation duration <90 days, 37 due to the need for a caregiver responsible for medications). A total of 147 patients were enrolled, of whom 13 (8.8%) were lost to follow-up. Therefore, data were analyzed from 134 patients (mean [SD] age, 55 [14.2] years [range, 19–87 years]), who were followed up for a mean (SD) duration of 272 (87) days. The total mean TTR was 64.7%, which is comparable to values achieved in clinical trials. The good-control group had 61 patients (45.5%) (mean TTR, 77.7% [8.5%]) and the poor-control group had 73 patients (54.5%) (mean TTR, 50.4 [11.7%]). On multivariate logistic regression analysis, high-quality anticoagulation was independently associated with regular vitamin K intake, expressed by its variability in daily dosage (odds ratio [OR] = 0.79; 95% CI, 0.64–0.98); male sex (OR = 2.41; 95% CI, 1.06–5.49); duration of anticoagulation treatment >2 months (OR = 3.23; 95% CI, 1.25–8.36); presence of family support (OR = 3.32; 95% CI, 1.16–9.48); functional and cognitive ability to take medications as prescribed, defined as good medication management capacity (MMC; as assed using the Drug Regimen Unassisted Grading Scale) (OR = 4.18; 95% CI, 1.63–10.68); and no regular use of alcohol (OR = 8.59; 95% CI, 1.45–51.09).

Conclusions

The data suggest that independent predictors of high-quality oral anticoagulation included regular vitamin K intake, male sex, duration of anticoagulation treatment >2 months, presence of family support, good MMC, and no regular alcohol use. These findings may help clinicians to decide whether to start anticoagulation in intermediate-risk patients, to identify patients who will require closer attention on their anticoagulation management, and to direct their efforts to improve the quality of oral anticoagulation.

Introduction

Oral anticoagulation with vitamin K antagonists has well-established efficacy in various clinical conditions associated with thromboembolic events and is used throughout the world.1 Despite extensive evidence of its effectiveness, oral anticoagulation may lead to adverse events, mainly bleeding. A strong relationship between supra- or subtherapeutic anticoagulation and adverse outcomes (bleeding or thromboembolic events, respectively) has been observed in a large number of studies.2, 3, 4, 5 Consequently, a narrow therapeutic range is necessary for antithrombotic efficacy and low risk for bleeding. To achieve this, warfarin use means dedicated monitoring of drug effect and dose tailoring in anticoagulation clinics or self-monitoring strategies.1, 6 Despite promising results with newer drugs that no longer require this effort, vitamin K antagonists are likely to be in use for the next years.7, 8, 9

Thus, high-quality anticoagulation management aims to achieve maximum effectiveness with minimum risk. The most recommended measure to evaluate the quality of anticoagulation is the estimate of percentage of time in therapeutic range (TTR), that is, the percentage of time patients spend within therapeutic international normalized ratio (INR) limits.10, 11 TTR has been reported to correlate strongly with the major clinical outcomes of hemorrhage or thrombosis1, 3, 4, 5 and is considered a reliable measure of anticoagulation quality.10, 11 Although there is no well-defined cutoff, 2 recent reviews reported that a TTR of ∼66% is a benchmark to define high-quality anticoagulation.10, 11

To achieve this high-quality anticoagulation, it is of utmost importance to know which factors are associated with long-term anticoagulation control in clinical practice. Regarding the management model, it has been well-established that better TTRs are achieved when anticoagulant therapy is managed by an anticoagulation clinic or by self-management compared with usual care provided by personal physicians.6, 12, 13, 14 Regarding patient-level characteristics, it has been reported that alcoholism, heart failure, cancer, drug interactions, poor adherence to therapy, inadequade patient guidance, patterns of vitamin K intake, and recent initiation of anticoagulation may interfere with the quality of anticoagulation.15, 16, 17, 18, 19, 20, 21, 22, 23 However, few studies have assessed the contribution of multiple factors simultaneously.

Expanding the knowledge on factors associated with quality of oral anticoagulation has some important implications. Identifying factors that may be amenable to interventions may focus anticoagulation providers' practice to achieve high-quality management. Identifying predictors of oral anticoagulation quality may help physicians to decide whether to start anticoagulation in intermediate-risk patients (eg, those with atrial fibrillation or at intermediate risk for stroke), and/or to identify patients who will require closer attention to their anticoagulation management. In fact, the quality of anticoagulation concerns individual patients, due to its burden, health care professionals involved in anticoagulation, and also public health care members—the latter not only by the impact on rates of thrombotic and hemorrhagic events but also by the fact that aging of the population means increasing prevalence of conditions that require this treatment. Finally, it also affects the implementation of newer anticoagulant drugs, as its cost-effectiveness compared with that of warfarin is dependent on the quality of warfarin control (ie, TTR).7 That is, the cost-effectiveness of newer anticoagulants is expected to be greater in individual patients with poor warfarin control than in patients with high-quality anticoagulation control.9

This study was designed to assess the potential predictors of high-quality anticoagulation control in an extended follow-up of patients at an anticoagulation clinic.

Section snippets

Study Population

A prospective observational study was conducted from December 2006 to January 2008, enrolling all patients attending the anticoagulation clinic of the Hospital Municipal Odilon Behrens (a public hospital in Belo Horizonte, Brazil). Eligible patients were ≥18 years of age, taking oral anticoagulation intended to last for a minimum of 90 days from enrollment, and needed little or no assistance in taking medications. Patients already on oral anticoagulants and those starting oral anticoagulation

Results

Participation was requested from all 233 patients followed up at the anticoagulation clinic. Eighty-six patients did not meet the inclusion criteria (49 due to intended anticoagulation duration <90 days, 37 due to need of a caregiver responsible for medications). A total of 147 patients were enrolled, of whom 13 (8.8%) were lost to follow-up before 90 days. Therefore, data from 134 patients were analyzed (mean [SD] age, 55 [14.2] years [range, 19–87 years]). The mean duration of follow-up was

Discussion

The TTR of 64.7% found in this study is comparable to those reported in international publications. A systematic review encompassing 67 studies in 50,208 patients found the TTR varied according to the model of anticoagulation management.6 Among studies of warfarin, the TTRs were reported as 53.1% in usual care, 62.1% in anticoagulation clinics, 66.3% in clinical trials, and 71.5% in models with self-management strategy. Although the latter was associated with the best anticoagulation control,

Conclusion

The findings from the present study suggest that male sex, duration of anticoagulation >2 months, presence of family support, regular vitamin K intake, no regular alcohol use, and good MMC are independent predictors of high-quality oral anticoagulation.

Conflict of Interest

The authors have indicated that they have no conflicts of interest with regard to the content of this article.

Acknowledgments

Dr. Costa contributed to the design of the study, data collection, analysis and interpretation, and manuscript preparation. Dr. Lamego contributed to the design of the study, data collection, and manuscript preparation. Dr. Colosimo contributed data analysis and interpretation and manuscript preparation. Dr. Valacio contributed to the design of the study, analysis and interpretation, and manuscript preparation. Dr. Moreira contributed to the design of the study, data analysis and

References (54)

  • T.I. Shireman et al.

    Development of a contemporary bleeding risk model for elderly warfarin recipients

    Chest

    (2006)
  • E. Sconce et al.

    Vitamin K supplementation can improve stability of anticoagulation for patients with unexplained variability in response to warfarin

    Blood

    (2007)
  • E.K. Rombouts et al.

    Daily vitamin K supplementation improves anticoagulant stability

    J Thromb Haemost

    (2007)
  • J.M. Spahn et al.

    State of the evidence regarding behavior change theories and strategies in nutrition counseling to facilitate health and food behavior change

    J Am Diet Assoc

    (2010)
  • S.J. Connolly et al.

    Benefit of oral anticoagulant over antiplatelet therapy in atrial fibrillation depends on the quality of international normalized ratio control achieved by centers and countries as measured by time in therapeutic range

    Circulation

    (2008)
  • M. Jones et al.

    Evaluation of the pattern of treatment, level of anticoagulation control, and outcome of treatment with warfarin in patients with nonvalvar atrial fibrillation: a record linkage study in a large British population

    Heart

    (2005)
  • N.J. Veeger et al.

    Individual time within target range in patients treated with vitamin K antagonists: main determinant of quality of anticoagulation and predictor of clinical outcomeA retrospective study of 2300 consecutive patients with venous thromboembolism

    Br J Haematol

    (2005)
  • R.H. White et al.

    Comparison of outcomes among patients randomized to warfarin therapy according to anticoagulant controlResults From SPORTIF III and V

    Arch Intern Med

    (2007)
  • S.V. Shah et al.

    Cost-effectiveness of dabigatran for stroke prophylaxis in atrial fibrillation

    Circulation

    (2011)
  • J.D. Douketis

    Dabigatran as anticoagulant therapy for atrial fibrillation

    Pol Arch Med Wewn

    (2011)
  • S. Kaatz

    Determinants and measures of quality in oral anticoagulation therapy

    J Thromb Thrombolysis

    (2008)
  • K. Phillips et al.

    Outpatient management of oral vitamin K antagonist therapy: defining and measuring high-quality management

    Expert Rev Cardiovasc Ther

    (2008)
  • S.J.A. Wilson et al.

    Comparing the quality of oral anticoagulant management by anticoagulation clinics and by family physicians: a randomized controlled trial

    CMAJ

    (2003)
  • M.B. Nichol et al.

    Quality of anticoagulation monitoring in nonvalvular atrial fibrillation patients: comparison of anticoagulation clinic versus usual care

    Ann Pharmacother

    (2008)
  • J.M. Garcia-Alamino et al.

    Self-monitoring and self-management of oral anticoagulation

    Cochrane Database Syst Rev

    (2010)
  • K. Demirkan et al.

    Response to warfarin and other oral anticoagulants: effects of diseases states

    South Med J

    (2000)
  • T. Khan et al.

    Dietary vitamin K influences intra-individual variability in anticoagulant response to warfarin

    Br J Haematol

    (2004)
  • Cited by (0)

    View full text