Inclisiran as Adjunct Lipid-Lowering Therapy for Patients with Cardiovascular Disease: A Cost-Effectiveness Analysis.

Background: Inclisiran inhibits hepatic synthesis of proprotein convertase subtilisin-kexin type 9 (PCSK9). The comparison of inclisiran with statin versus statin alone in the ORION-10 trial demonstrated significant reductions in low-density lipoprotein cholesterol (LDL-C). Our study explored whether the use of inclisiran with statin versus statin alone for secondary prevention of cardiovascular events is cost effective from the Australian healthcare perspective, based on the price of currently available PCSK9 inhibitors.

Methods: A Markov model was developed based on the ORION-10 trial to model outcomes and costs incurred by patients over a lifetime analysis. The three health states were 'alive with cardiovascular disease (CVD)', 'alive with recurrent CVD', and 'dead'. Cost and utilities were estimated from published sources. The cost of inclisiran was estimated from the annual cost of evolocumab, a PCSK9 inhibitor currently available in Australia (AU$6334, based on 2020 data). Outcomes of interest were incremental cost-effectiveness ratios (ICERs) in terms of cost per quality-adjusted life-year (QALY) and cost per year of life saved (YoLS). All costs, QALYs and YoLS were discounted at 5% per annum in line with Australian standards.

Results: Among 1000 subjects followed-up over a lifetime analysis, inclisiran with statin compared with statin alone prevented 235 non-fatal myocardial infarctions (NFMIs; 151 NFMI and 84 repeat NFMI cases) and 114 coronary revascularisation cases, and increased years of life by 0.549 (discounted) and QALYs by 0.468 (discounted). At an annual price of AU$6334, the net marginal cost was AU$58,965 per person. The above values equated to ICERs of AU$107,402 per YoLS and AU$125,732 per QALY gained. Assuming a willingness-to-pay threshold of AU$50,000, inclisiran would have to be priced 60% lower than other available PCSK9 inhibitors to be considered cost effective.

Conclusions: As an adjunct therapy to statin treatment in those who have persistently elevated LDL-C despite optimal statin therapy, inclisiran is effective in reducing cardiovascular events in patients with atherosclerotic CVD. Inclisiran is not cost effective from the Australian healthcare perspective, assuming acquisition costs of current PCSK9 inhibitors. The cost of inclisiran would have to be 60% lower than that of evolocumab.