Cost-Effectiveness of Inclisiran as Add-on Therapy to Standard-of-Care for the Secondary Prevention of Cardiovascular Events in Patients with Elevated LDL Cholesterol

OBJECTIVES: Unlike proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (evolocumab and alirocumab), inclisiran is a small interfering RNA that inhibits PCSK9. Inclisiran currently has no published results on cardiovascular outcomes. This study aims to gain a preliminary understanding of the cost-effectiveness of inclisiran, as add-on therapy for the secondary prevention of cardiovascular disease, in patients with elevated low-density lipoprotein cholesterol (LDL-C) while on standard-of-care in the Singapore setting, using LDL-C as a surrogate outcome.

METHODS: A Norwegian peer-reviewed cost-effectiveness model for inclisiran, which utilized a dynamic Markov cohort model, was adapted to the local setting. The model consists of stroke and acute coronary syndrome (includes myocardial infarction and unstable angina) event states and corresponding post-event states. Transition probabilities were adjusted based on LDL-C lowering effects shown in ORION-10, the pivotal trial for inclisiran, using the rate ratio between LDL-C change and probability of cardiovascular events from the Cholesterol Treatment Trialists’ Collaboration meta-analysis. Costs were sourced from public healthcare institutions in Singapore.

RESULTS: Compared to placebo, treatment with inclisiran resulted in higher costs (SGD30,125 [USD 22,582] incremental cost) and higher effectiveness (0.51 QALY gained) leading to an incremental cost-effectiveness ratio (ICER) of SGD 58,500/ QALY (USD 43,853/ QALY). The ICER increased to SGD 63,700/ QALY (USD 47,751/ QALY) when using the lower bound of the 95% confidence interval on the estimated LDL-C effect on reducing probability of cardiovascular events.

CONCLUSIONS: This study provides an initial understanding of the value of inclisiran using LDL-C as a surrogate outcome but remains highly uncertain given the lack of cardiovascular outcomes data.