Due to a high risk of thromboembolism in patients undergoing major orthopaedic surgery it has become standard practice to give thromboprophylactic treatment to these patients. Pharmaceutical interventions with or without addition of mechanical methods are recommended.
This project, commissioned by Helse Bergen HF Ortopedisk klinikk, examined thromboprophylaxis with rivaroxaban or dabigatran compared with low-molecular weight heparins (LMWH, i.e . enoxaparin and dalteparin) with regard to efficacy, safety and cost-effectiveness in patients undergoing elective total hip or knee replacement surgery.
We conducted a systematic review of the literature and made cost-effectiveness analyses based on a model that calculated quality-adjusted life years and life time costs.
The main findings were that:
- We did not find statistically significant differences between dabigatran and enoxaparin for mortality, pulmonary embolism, deep vein thrombosis or major bleeding. The quality of the evidence ranged from very low to moderate.
- For rivaroxaban compared with enoxaparin we found statistically a significant reduction in deep vein thrombosis, but also a trend towards increased risk of major bleeding. For mortality and pulmonary embolism there were no statistically significant differences between treatments. The quality of the evidence ranged from very low to moderate.
- Our results indicate a great uncertainty regarding which strategy is the most cost-effective. However, rivaroxaban and enoxaparin had a slightly higher probability of being cost-effective alternatives for patients undergoing total hip or knee replacement, respectively.
- The results of our model analysis of the uncertainty surrounding each group of parameters indicated that more research on efficacy data would have the greatest impact on reducing decision uncertainty.
After surgical procedures, long term immobilization or certain medical conditions, such as undesirable blood clot (thrombus) formation may occur. This can slow or even block blood circulation.
Due to a high risk of thromboembolism in patients undergoing major orthopaedic surgery, it has become standard practice to give thromboprophylactic treatment. In general, pharmaceutical interventions with or without addition of mechanical methods are recommended. During 2009 two new pharmaceutical treatment options became available on the Norwegian market: rivaroxaban and dabigatran. Both are given orally, in contrast to low molecular weight heparins (LMWH, i.e. enoxaparin and dalteparin), which are given as subcutaneous injections.
In this report we compared LMWH to the new oral treatment options in order to assess the relative efficacy and cost-effectiveness of the different options.
This report was conducted as a health technology assessment. It consists of a systematic review of the literature on clinical efficacy and safety as well as a health economic analysis of the new oral anticoagulants compared with LMWH.
We searched for systematic reviews and randomized controlled trials in relevant bibliographic databases. Trials were assessed by two independent reviewers and combined into meta-analyses of four outcomes: overall mortality, deep vein thrombosis (DVT), pulmonary embolism (PE) and bleeding events. The quality of the evidence was evaluated using GRADE (Grading of Recommendations, Assessment, Development and Evaluation).
In order to assess the cost-effectiveness of alternative thromboprophylactic interventions, a decision model was developed. The two surgery types, hip and knee replacement, were modelled separately to reflect differences in the underlying risk of developing DVT, PE and major bleeding.
The model combined two modules; a decision tree for short-term prophylaxis (for a period of 90 days after surgery:, acute phase) and a Markov model for long-term complications (until patients are either dead or 100 years old: chronic phase).
DVT, PE and major bleeding events were modelled for the acute phase. The quality-adjusted life-years (QALYs) and costs arising from these events were modelled over the patient’s lifetime, including treatment of post-thrombotic syndrome (PTS) and recurrent VTE. Efficacy estimates were taken from the systematic review part of this report. Quality of life data were extracted from published literature. Costs of medications were based on prices from the Norwegian Medicines Agency.
We performed probabilistic sensitivity analyses, designed as a Monte Carlo simulation with 1 000 iterations, to explore the uncertainty surrounding our results.
- No head-to-head comparison of dabigatran versus rivaroxaban was identified.
- No studies comparing dabigatran or rivaroxaban to dalteparin were identified.
- We did not find statistically significant differences between dabigatran and enoxaparin for the outcomes mortality, PE, DVT or major bleeding. The quality of the evidence ranged from very low to moderate.
- For rivaroxaban compared with enoxaparin we found statistically significant decreases in DVT, but also a trend towards increased risk of major bleeding. For mortality and PE there were no statistically significant differences between treatments. The quality of the evidence ranged from very low to moderate.
- The included systematic reviews did not report on the primary endpoint post-thrombotic syndrome or any of our secondary outcomes (duration of hospital stay, re-submission to hospital, sick-leave, infections, re-operations or quality of life).
- Assuming a willingness to pay of NOK 500 000 per QALY gained, the probability of rivaroxaban as thromboprophylactic treatment after total hip replacement being cost-effective was 38%.
- Assuming the same willingness to pay, the probability of enoxaparin following TKR being cost-effective was 34%.
- The results of our analyses of the uncertainty surrounding different groups of parameters indicated that more research on the input variables is likely to change our base-case results. Efficacy data had the greatest impact on decision uncertainty.
Dabigatran and rivaroxaban seem to be well tolerated antithrombotic medicines. Their efficacy and safety in hip and knee replacement surgery are comparable with enoxaparin.
Our results showed that there is a great uncertainty regarding which strategy is the most cost-effective. However, rivaroxaban and enoxaparin had a slightly higher probability of being cost-effective alternatives for patients undergoing either total hip or knee replacement, respectively. The results of our analyses to explore the uncertainty surrounding each group of parameters indicated that more research on efficacy data would have the greatest impact on reducing decision uncertainty.
Norwegian Knowledge Centre for the Health Services summarizes and disseminates evidence concerning the effect of treatments, methods, and interventions in health services, in addition to monitoring health service quality. Our goal is to support good decision making in order to provide patients in Norway with the best possible care. The Centre is organized under The Directorate for Health, but is scientifically and professionally independent. The Centre has no authority to develop health policy or responsibility to implement policies.
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