3.2.1. Vitamin K antagonist anticoagulants

Warfarin is part of the coumarin class of Vitamin K antagonists (Table 1). Vitamin K antagonists have been the mainstay of oral anticoagulant therapy for more than 60 years. Their effectiveness has been established by well-designed clinical trials for several thromboembolic indications.⁴ Evidence from several randomized controlled trials (RCTs) shows that long-term anticoagulation therapy with warfarin reduces the risk of ischemic stroke by 68% in patients with non-valvular AF (NVAF).³

Table 1

Vitamin K Antagonists Available in Canada.

However, clinical use of Vitamin K antagonists requires vigilance because:

• they have complex pharmacokinetics and pharmacodynamics
• they have a narrow therapeutic window
• they require (and benefit from) regular laboratory monitoring through a standardized blood test [International Normalized Ratio (INR)]
• the dose response varies among patients
• they are subject to several drug and dietary interactions.⁴

3.2.2. Vitamin K antagonist anticoagulant management models

The effectiveness and safety of warfarin therapy depend on maintaining the INR in the optimal therapeutic range⁴ (between 2 and 3 for AF⁶). There is a relationship between the time in therapeutic INR range (TTR) and bleeding or thromboembolic events.⁴ The percentage of TTR is used as a marker for the quality of warfarin management. Evidence (from international clinical trials and observational studies on cardiac and other indications) demonstrated a wide spectrum of TTRs, varying from a lower range of 32% to 68% for usual care, to a higher 55% to 92% range for patient self-management (PSM).⁴

Usual care is 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.⁷ Physicians in this setting use their own judgment, without access to specialized anticoagulation tools or anticoagulation clinic staff and services.^{7, 8}

Approaches suggested by the literature⁴ to improve anticoagulant therapy include:

• anticoagulant monitoring services
• the use of point-of-care (POC) INR testing that allows patient self-testing (PST) or PSM of dose adjustment (combines self-testing with patient adjustment of their own doses)
• specialized tools to guide warfarin dose adjustment.

Anticoagulation monitoring services include a number of alternatives to usual care, from tertiary or community hospital-based anticoagulation clinics to primary-care settings and POC testing and dose adjustment by community pharmacies.⁹ Primary-care settings and hospital-based anticoagulation clinics may use computerized decision–support applications or other tools to guide warfarin dosing.^{4, 9} 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.⁹ Specialized anticoagulation tools refer to a broad range of products that can be used by clinicians to guide dosing of warfarin in their particular practice setting. These vary from a simple web-based or paper nomogram (e.g., University of Wisconsin dosing protocol¹⁰) to an online warfarin dose calculator (e.g., WarfarinDosing.org¹¹) to a computer application (e.g., DAWN software¹²).