Elsevier

International Journal of Cardiology

Volume 270, 1 November 2018, Pages 54-59
International Journal of Cardiology

Cost-effectiveness of rivaroxaban and aspirin compared to aspirin alone in patients with stable cardiovascular disease: An Australian perspective

https://doi.org/10.1016/j.ijcard.2018.06.091Get rights and content

Highlights

  • A large number of people with cardiovascular disease remain undertreated.

  • Rivaroxaban in addition to aspirin has been shown to reduce secondary CVD.

  • A Markov model was developed to predict the long-term treatment effect.

  • Rivaroxaban and aspirin is likely to be cost-effective compared to aspirin alone.

Abstract

Objective

In light of the Cardiovascular Outcomes for People using Anticoagulation Strategies (COMPASS) trial, our objective was to assess the cost-effectiveness, from the Australian healthcare perspective, of rivaroxaban in combination with aspirin versus aspirin alone for the prevention of recurrent cardiovascular disease among patients with stable atherosclerotic vascular disease.

Methods

A Markov model was developed using input data from the COMPASS trial to predict the clinical course and costs of patients over a 20-year time-horizon. The model comprised of three health states: ‘Alive without recurrent CVD’, ‘Alive after recurrent CVD’ and ‘Dead’. Costs were from the Australian public healthcare system perspective, and estimated from published sources, as were utility data. The costs of rivaroxaban were based on current acquisition prices on the Australian Pharmaceutical Benefits Schedule (PBS) and assumed as AUD$3.09/day. The main outcome of interest was the incremental cost-effectiveness ratio (ICER) in terms of cost per quality adjusted life year (QALY) gained, and cost per year of life saved (YoLS). Costs and benefits were discounted by 5.0% per year.

Results

Compared to aspirin alone, rivaroxaban plus aspirin was estimated to cost an additional AUD$12,156 (discounted) per person, but lead to 0.516 YoLS (discounted) and 0.386 QALYs gained (discounted), over 20 years. These equated to ICERs of AUD$23,560/YoLS and AUD$31,436/QALY gained. We have assumed a threshold of AUD$50,000/QALY gained to signify cost-effectiveness.

Conclusion

Compared to aspirin, rivaroxaban in combination with aspirin is likely to be cost-effective in preventing recurrent cardiovascular events in patients with stable atherosclerotic vascular disease.

Introduction

Although mortality from cardiovascular disease (CVD) has declined in developed countries over the past few decades, ischaemic heart disease and stroke remain the leading causes of disability worldwide [1]. Furthermore, there is a large proportion of the population with CVD that remains undertreated, meaning the preventable burden is large [2, 3]. The evidence for the efficacy of low-dose aspirin in secondary cardiovascular prevention is unequivocal, with pooled trial data showing that aspirin reduces the risk of recurrent major CVD events by 19.0% over the trial duration of 23 months [4].

In the wake of trials that established the net benefit of non-vitamin K antagonist oral anticoagulation (NOACs) compared to aspirin [5], warfarin [[6], [7], [8]] or placebo [9] in preventing systemic thromboembolic events among patients with non-valvular atrial fibrillation, more recent attention has turned to the use of NOACs among patients with previous CVD to reduce the likelihood of recurrent thromboembolic cardiovascular events. The recently-published Cardiovascular Outcomes for People using Anticoagulation Strategies (COMPASS) trial [10] was designed to assess the impact of rivaroxaban (a selective direct factor Xa inhibitor) (2.5 mg twice daily) plus aspirin (100 mg once daily) compared to rivaroxaban alone (5 mg twice daily) and aspirin alone (100 mg once daily) in patients with stable atherosclerotic vascular disease. Compared to patients assigned to aspirin alone, those assigned to rivaroxaban plus aspirin experienced fewer episodes of the primary outcome, a composite of cardiovascular death, stroke and myocardial infarction (MI), over a mean 23-month period of follow-up, the hazard ratio (HR) was 0.76 (95% confidence interval [CI], 0.66–0.86, p < 0.001) [10]. However, more bleeding events occurred, with a HR of 1.70 (95% CI, 1.40–2.05, p < 0.001) [10]. Rivaroxaban alone did not confer any statistically significant benefits over aspirin alone, but was associated with a higher risk of bleeding. Therefore the results of the COMPASS study suggest the potential role of low-intensity anticoagulation with NOACs in addition to aspirin for secondary cardiovascular prevention.

Although a number of publications explore the cost effectiveness of low-dose aspirin in secondary prevention of CVD [2, 11, 12] and rivaroxaban in prevention of stroke or systemic embolism[13, 14], no analysis has been undertaken to evaluate the cost effectiveness of rivaroxaban in combination with aspirin in secondary prevention of CVD.

In light of the COMPASS study, the objective of our study was to examine the potential cost-effectiveness of rivaroxaban in combination with aspirin compared to aspirin alone for the secondary prevention of CVD (comprising MI and stroke) in patients with stable atherosclerotic vascular disease, from the perspective of the Australian public healthcare system.

Section snippets

Methods

Model structure.

A Markov model with a cycle length of 1 year was developed to simulate the clinical course and costs of rivaroxaban in combination with aspirin versus aspirin alone in patients with stable atherosclerotic vascular disease, as per the COMPASS trial. The model comprised of three health states: ‘Alive without recurrent CVD’, ‘Alive after recurrent CVD’ and ‘Dead’ (Fig. 1). For the health states ‘Alive without recurrent CVD’ and ‘Alive after recurrent CVD’, the transition states

Results

Over a 20-year time horizon, the model predicted that the NNT to prevent one additional acute CVD (non-fatal MI/stroke) event for rivaroxaban plus aspirin versus aspirin alone was 39.2. The equivalent NNTs for cardiovascular death and overall death were 395.5 and 14.3 respectively. The NNH for major bleeding was 2.42 (Appendix 4).

Discussion

Our cost-effectiveness analysis indicates that in patients with stable atherosclerotic vascular disease, the use of rivaroxaban plus aspirin is likely to be cost-effective compared to aspirin alone in the context of the Australian public healthcare system. The base-case analysis indicated an ICER of just over AUD $30,000 per QALY gained, and cost-effectiveness was maintained throughout a range of plausible scenarios. In our analysis, we assumed a threshold of AUD $50,000 per QALY gained to

Conclusion

Compared to aspirin, rivaroxaban in combination with aspirin is very likely to be cost-effective in preventing recurrent cardiovascular events in patients with stable atherosclerotic vascular disease, from the perspective of the Australian healthcare system. The robustness of this conclusion was confirmed by sensitivity analyses.

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