Budget impact analysis of warfarin reversal therapies among hip fracture patients in Finland

Finland, like many other countries, has a growing population of elderly patients – amongst other issues, this means that the incidence of hip fractures is increasing. Early surgery (within 36–48 hours) for hip fractures is accepted as best practice. Rapid intervention has been demonstrated to reduce mortality, morbidity and length of hospital stay, and leads to an earlier return to independent living. As the characteristic hip fracture patient is elderly and frail, comorbid disease is common, and pre-existing anticoagulation treatment is a frequent cause for delay.

There are several potential reversal strategies for warfarin (the most commonly used oral anticoagulant) – warfarin cessation, vitamin K administration, fresh frozen plasma (FFP) and prothrombin complex concentrates (PCC). Warfarin cessation is an ideal strategy for elective surgery, but may take several days for INR normalisation – making it impractical in an emergency scenario. Vitamin K administration is cost effective, but will take ~24 hours and may still prove ineffective, resulting in delays. FFP is more rapid than vitamin K, but has a large infusion volume and the potential for transfusion reactions. PCC is also rapid and avoids many of the negative clinical aspects associated with FFP, but has a high cost.

There were 4,418 patients with a first fractured neck of femur in Finland in 2009 – limited to community-based patients over the age of 50 years with a defined treatment period in the surgical unit. Estimates for the prevalence of warfarin therapy were based on that of the general population. For the base-case analysis, an initial INR of 3.0 was assumed, and a body-weight of 70 kg – the target INR was assumed to be ≤1.5. To estimate current practice, a questionnaire was sent to all chief anaesthesiologists (n=27), asking for their standard treatment for a clinical scenario involving a fractured neck of femur in a patient on warfarin. Factors considered in the cost analysis were: cost of hospitalisation prior to surgery, cost of laboratory tests, unit cost of therapy plus wastage. Resource use was calculated based on current best practice. The overall costs of the different potential treatments were then calculated and compared.

An estimated 410 patients with fractured neck of femur would require treatment for warfarin reversal annually in Finland. When the overall cost analysis was performed, the least costly option was vitamin K, followed by PCC. The high drug costs of PCC were partially offset by the reduced healthcare resource use. Warfarin cessation was the most costly option due to increased length of pre-operative stay. When clinical scenarios were reviewed, combination PCC plus vitamin K was the most common approach, but all options were used to differing degrees – this was assumed to be representative of practice as a whole. The transition from current practice to 100% use of either vitamin K, PCC or FFP would result in cost savings.

In their discussion, the authors reiterate that vitamin K and PCC were the least costly options when accounting for direct healthcare costs prior to surgery. Most of the cost of vitamin K was related to treatment delays, while PCC was the most expensive drug, but caused the least delay. The pure comparison is perhaps less useful than it seems initially, as clinical factors and contraindications make 100% uptake impractical. A dose of 1 mg of vitamin K orally provides effective reversal at 24 hours in approximately 66% of patients; when a dose of 3 mg is given intravenously, this rises to 90%. Vitamin K is less effective in severely deranged coagulation, and creates additional post-operative delays in re-establishing therapeutic anticoagulation – often requiring bridging therapy with low molecular weight heparin and repeated INR testing.

Limitations acknowledged by the authors are the potential difficulty of extrapolation of the study, as it was based on the pricing and demographics of one country, and the fact that the impact analysis was based on a limited number of anaesthesiologists’ responses. In addition, the study does not explore the post-operative delays nor costs relating to morbidity and mortality raised by delays. They also do not explore the potential for a treatment pathway that combines vitamin K administration with a subsequent INR check and treatment with PCC if needed.

This study reveals that the costs associated with a treatment may end up higher than the treatment itself, and provides a case for the use of vitamin K or PCC as valid warfarin reversal strategies when urgent surgery is required.