Cost-effectiveness of cholesterol-lowering drugs for secondary cardiovascular prevention in the UK: ezetimibe, evolocumab, and alirocumab

Abstract

Abstract Background Despite statin treatment, patients with elevated low-density lipoprotein cholesterol (LDL-C) levels remain at high risk for acute cardiovascular events. Ezetimibe, evolocumab, and alirocumab were consequently developed to reduce the risk of recurrent ischemic events in patients with established cardiovascular diseases by 6%, 15%, and 15%, respectively. However, these novel treatments must demonstrate both clinical efficacy and cost-effectiveness to promote long-term adoption by patients, physicians, and insurers. Objective To assess the cost-effectiveness of statins in combination with ezetimibe, evolocumab, and alirocumab for secondary cardiovascular prevention from the perspective of England's National Health Service (NHS). Methods The incidence of major adverse cardiovascular events, including, myocardial infarction, stroke, angina, and coronary revascularization, was simulated with a Markov cohort model. The model was populated with transition probabilities and hazard ratios derived from cardiovascular outcome trials for statin combinations with ezetimibe (IMPROVE-IT), evolocumab (FOURIER), and alirocumab (ODYSSEY). Costs and utilities were retrieved from previous literature. Principle outcomes of interest were the incremental cost-effectiveness ratios (ICER) per quality-adjusted life year (QALY) gained in 2021 Great Britain Pounds (£). Univariate, scenario, willingness-to-pay, and probabilistic sensitivity analyses were conducted to assess the robustness of results. Results For secondary cardiovascular prevention, ezetimibe in combination with statins increased QALYs gained by 0.60 at cost reductions of −£2,529 (ICER: −4,231 £/QALY) per patients compared to statin monotherapy. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors provided incremental QALYs of 0.53 and 0.86 at costs of £45,279 and £46,375 for evolocumab (ICER: 75,283 £/QALY) and alirocumab (ICER: 40,708 £/QALY), respectively. At the NHS' willingness-to-pay threshold of 30,000 £/QALY, there is 100% probability for ezetimibe and 0% probability for PCSK9 inhibitors to be cost-effective in secondary prevention. Results remained robust under univariate, scenario, and probabilistic sensitivity analyses. Conclusions Ezetimibe is cost-effective for secondary cardiovascular prevention at an annual price of £346 in the UK. For PCSK9 inhibitors, discounts of −37% to −53% on alirocumab's (£4,412) and evolocumab's (£4,467) prices are necessary to achieve cost-effectiveness. Funding Acknowledgement Type of funding sources: None.