Feasibility Study of the Fearon Algorithm in Warfarin Patient Self-Management

Vitamin K antagonists (VKA) such as warfarin are very effective anticoagulants for the prevention of thrombosis. However, warfarin is also a leading cause of emergency room visits and hospitalizations for bleeding complications. A laboratory test of coagulation, the prothrombin time (PT), is used to monitor warfarin's anticoagulant effect on the hemostatic system. For warfarin monitoring the PT is expressed as an international normalized ratio (INR) to reduce the impact of interlaboratory PT variation. For individuals not on warfarin, the INR is about 1.0 while most patients on VKA require an INR between 2.0 and 3.0 to best balance the competing risks of thromboembolism and bleeding.

The INR response to warfarin can fluctuate as a result of changes in health status, interactions with other drugs, changes in dietary vitamin K intake, alcohol consumption, as well as for no apparent reason. In addition, the response to a change in warfarin dose varies between patients as does the time required for the INR response to reach steady state. A substantial proportion of patients treated with warfarin have stable INRs and remain on the same weekly maintenance dose month after month. Patients with variable INRs resulting in a low proportion of time in therapeutic INR range (TTR) have a higher risk of both bleeding complications and thromboembolic events. Good TTR is generally considered to be over 60% and TTR above 72% is considered excellent. One quarter to one third of patients have unstable INR results and require more frequent monitoring and warfarin dosing adjustments. This is demanding for patients and also for health care systems. Many of these patients remain unstable even when drug interactions, irregular dietary vitamin K intake, and missed warfarin doses have been excluded indicating the need for improved approaches to adjusting VKA doses in response to out-of-range INRs.

Interventions aimed at improving INR stability during warfarin therapy have been investigated. Using warfarin dosing algorithms is one intervention associated with improved INR stability and decreased risk for thromboembolic and bleeding complications and lower mortality. Patient self-management (PSM) of warfarin therapy using INRs obtained by patients in their home environment using point-of-care INR monitoring devices has also been shown to improve INR stability and decrease the risk of thromboembolic complications and mortality. Unfortunately, the US healthcare system lags behind other countries in widespread adoption of these evidence-based interventions for improving warfarin therapeutic outcomes.

Potential explanations for the underutilization of warfarin dosing algorithms and PSM include mistrust of algorithms among anticoagulation providers, complexity associated with algorithm use, lack of algorithm validation, and the effort required to train patients in self-management. As most patients receiving warfarin therapy in the US are outside the targeted INR range approximately 40% of the time, there is a critical need for approaches that remove barriers to adopting proven interventions like using warfarin dosing algorithms and PSM.

The Fearon Algorithm Mike Fearon, PhD has developed a patient-individualized warfarin dosing algorithm (the Fearon Algorithm [FA]) to predict INR results using parameters derived from the patient's prior warfarin dosing history. Key FA parameters not available with existing warfarin dosing algorithms include: 1) warfarin dose sensitivity (i.e. the likely change in INR from an increment change in warfarin dose), 2) optimal warfarin tablet strength for a given patient, 3) time required to reach INR steady state, and 4) inherent variability of the INR.