Excerpt

Warfarin is an oral anticoagulant in the drug class of vitamin K antagonists. It is often used for stroke prevention in patients with atrial fibrillation (AF) at high risk for stroke who have no contraindications. Warfarin and related anticoagulants have consistently been shown to reduce the risk of stroke in patients with AF by more than 60% compared with no treatment, and by 30% to 40% compared with low-dose aspirin. Long-term anticoagulation with vitamin K antagonists is typically required for prevention and treatment of thromboembolism in patients with AF and other high-risk groups, such as patients with mechanical heart valves, venous thromboembolism, pulmonary embolism, or peripheral vascular disease. However, warfarin use has some disadvantages, including numerous food and drug interactions, the need for frequent laboratory monitoring, and the risk of bleeding complications.

The effectiveness and safety of warfarin depends on maintaining its dose at sufficient levels to keep patient international normalized ratio (INR) within the therapeutic range. Current Canadian guidelines recommend a target INR range of 2.0 to 3.0. The percentage of time spent in the therapeutic range (TTR) depends on the quality of dose management.

TTR can be calculated by different methods. The simplest involves calculating the proportion of INR test results that fall within the therapeutic range, but fails to account for actual time spent in range. The most common method in clinical studies is the Rosendaal linear interpolation method. This method adds each patient’s time within the therapeutic range and divides by the total time of observation. This assumes that between-test INR varies linearly. Another common method is the half-time interpolation method, by which the total time of follow-up with INR in range is divided by the total time. Half the time between two tests is allocated to the first INR value, and half to the second. Different studies use different methods to calculate TTR, which should be taken into account when comparing TTR values.

Specialized anticoagulation services have been developed to optimize warfarin dosing management. These services can generally be defined as tertiary or community hospital-based anticoagulation clinics, primary care settings, point-of-care (POC) testing and dose adjustment by community pharmacies, and patient self-testing (PST) and patient self-management (PSM) using a POC device. The primary care anticoagulation setting involves a family practice group or family health team where nurses, pharmacists, or physicians are responsible for managing warfarin therapy. Primary care settings and hospital-based anticoagulation clinics may use computerized decision-support applications or other means to guide warfarin dosing. This is in contrast to usual care (UC), which may be defined as warfarin dose adjustment managed by a physician working in a private practice setting that not only addresses anticoagulation management, but also other medical problems. Physicians in this setting use their own judgment without access to specialized anticoagulation tools, or specialized anticoagulation staff and services.

The purpose of this report is to compare the clinical effectiveness of different models of warfarin management. A systematic review of the clinical evidence was conducted for this purpose.

Contents

• ABBREVIATIONS
• 1. INTRODUCTION
  • 1.1 COMPUS Expert Review Committee
• 2. CONTEXT AND POLICY ISSUES
• 3. RESEARCH QUESTIONS
• 4. KEY FINDINGS
• 5. METHODS
  • 5.1 Literature Search Strategy
  • 5.2 Selection Criteria and Method
  • 5.3 Exclusion Criteria
  • 5.4 Data Extraction Strategy
  • 5.5 Critical Appraisal of Individual Studies
  • 5.6 Data Analysis Methods
• 6. RESULTS
  • 6.1 Quantity of Research Available
  • 6.2 Study Characteristics
  • 6.3 Critical Appraisal of Individual Studies
  • 6.4 Data Analyses and Synthesis
• 7. DISCUSSION
  • 7.1 Summary of Evidence
  • 7.2 Limitations
• 8. CONCLUSIONS AND IMPLICATIONS FOR DECISION- OR POLICY-MAKING
• REFERENCES
• APPENDIX 1 EXPERT COMMITTEE AND CONTRIBUTORS
• APPENDIX 2 SELECTION OF INCLUDED STUDIES
• APPENDIX 3 CHARACTERISTICS OF INCLUDED SYSTEMATIC REVIEWS
• APPENDIX 4 CHARACTERISTICS OF INCLUDED PRIMARY STUDIES

This report is prepared by the Canadian Agency for Drugs and Technologies in Health (CADTH). This report contains a review of existing public literature, studies, materials, and other information and documentation (collectively the “source documentation”) available to CADTH at the time it was prepared, and it was guided by expert input and advice throughout its preparation.

The information in this report is intended to help health care decision-makers, patients, health care professionals, health systems leaders, and policy-makers make well-informed decisions and thereby improve the quality of health care services. The information in this report should not be used as a substitute for the application of clinical judgment in respect to the care of a particular patient or other professional judgment in any decision-making process, nor is it intended to replace professional medical advice. While CADTH has taken care in the preparation of this report to ensure that its contents are accurate, complete, and up-to-date, CADTH does not make any guarantee to that effect. CADTH is not responsible for any errors or omissions or injury, loss, or damage arising from or as a result of the use (or misuse) of any information contained in or implied by the information in this report.

CADTH takes sole responsibility for the final form and content of this report. The statements, conclusions, and views expressed herein do not necessarily represent the view of Health Canada or any provincial or territorial government.

Production of this report is made possible through a financial contribution from Health Canada.