COST-EFFECTIVENESS OF INCLISIRAN VS. EZETIMIBE MONOTHERAPY IN LOW-RISK PRIMARY HYPERCHOLESTEROLEMIA: A MARKOV MODEL
Author(s)
Diamant Gashi, MD, Yi Yang, PhD, MD;
University of Mississippi, University, MS, USA
University of Mississippi, University, MS, USA
OBJECTIVES: To evaluate the cost-effectiveness of inclisiran vs. ezetimibe monotherapy in low-risk adults with primary hypercholesterolemia and quantify decision uncertainty.
METHODS: A Markov model (6 states: event‑free, post‑myocardial infarction (MI) year 1/year ≥2, post‑stroke year 1/year ≥2, dead) was constructed from a US payer perspective. Cohort entry age was 46 years and time horizon was 10 years in base case. Costs/quality-adjusted life years (QALYs) were discounted at 3% with half-cycle correction. Model inputs were obtained from published meta-analysis of clinical trial and other literature. Trial low-density lipoprotein (LDL)-C effects (inclisiran -46.5%, ezetimibe -11.2%) were adherence-adjusted. All costs were adjusted to 2025 US$. LDL-C change was mapped to MI and stroke using Cholesterol Treatment Trialists’ per mmol/L relative risk reductions (MI 0.77; stroke 0.85). Baseline atherosclerotic cardiovascular disease risk reflected trial population. US life tables informed background mortality. Scenario analyses tested biologic efficacy (adherence =100% for effectiveness) and a lifetime horizon (40 years, age 46-86). One-way and probabilistic sensitivity analysis (PSA) were conducted to test base-case model robustness.
RESULTS: In base case, inclisiran incurred total costs of $59,576 with 8.2075 QALYs, compared with ezetimibe at $607 and 8.2039 (ICER =$16.5M/QALY). Under biologic efficacy, an ICER of $14.1M/QALY was obtained while model with lifetime horizon yielded an ICER of $6.0M/QALY. Results from one-way SA support base-case results. Threshold analysis suggested that inclisiran would require a price reduction of approximately 98% to approach cost-effectiveness compared to ezetimibe at the willingness-to-pay (WTP) of $150,000/QALY. PSA indicated <1% probability of inclisiran to be cost-effective at WTP of $150,000/QALY.
CONCLUSIONS: In primary prevention among low risk adults, inclisiran monotherapy is highly unlikely to be cost‑effective vs. ezetimibe at current US prices; results are robust to biologic‑efficacy and lifetime‑horizon assumptions and are driven primarily by high drug cost and low baseline risk.
METHODS: A Markov model (6 states: event‑free, post‑myocardial infarction (MI) year 1/year ≥2, post‑stroke year 1/year ≥2, dead) was constructed from a US payer perspective. Cohort entry age was 46 years and time horizon was 10 years in base case. Costs/quality-adjusted life years (QALYs) were discounted at 3% with half-cycle correction. Model inputs were obtained from published meta-analysis of clinical trial and other literature. Trial low-density lipoprotein (LDL)-C effects (inclisiran -46.5%, ezetimibe -11.2%) were adherence-adjusted. All costs were adjusted to 2025 US$. LDL-C change was mapped to MI and stroke using Cholesterol Treatment Trialists’ per mmol/L relative risk reductions (MI 0.77; stroke 0.85). Baseline atherosclerotic cardiovascular disease risk reflected trial population. US life tables informed background mortality. Scenario analyses tested biologic efficacy (adherence =100% for effectiveness) and a lifetime horizon (40 years, age 46-86). One-way and probabilistic sensitivity analysis (PSA) were conducted to test base-case model robustness.
RESULTS: In base case, inclisiran incurred total costs of $59,576 with 8.2075 QALYs, compared with ezetimibe at $607 and 8.2039 (ICER =$16.5M/QALY). Under biologic efficacy, an ICER of $14.1M/QALY was obtained while model with lifetime horizon yielded an ICER of $6.0M/QALY. Results from one-way SA support base-case results. Threshold analysis suggested that inclisiran would require a price reduction of approximately 98% to approach cost-effectiveness compared to ezetimibe at the willingness-to-pay (WTP) of $150,000/QALY. PSA indicated <1% probability of inclisiran to be cost-effective at WTP of $150,000/QALY.
CONCLUSIONS: In primary prevention among low risk adults, inclisiran monotherapy is highly unlikely to be cost‑effective vs. ezetimibe at current US prices; results are robust to biologic‑efficacy and lifetime‑horizon assumptions and are driven primarily by high drug cost and low baseline risk.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
EE317
Topic
Economic Evaluation
Topic Subcategory
Thresholds & Opportunity Cost
Disease
SDC: Cardiovascular Disorders (including MI, Stroke, Circulatory), SDC: Diabetes/Endocrine/Metabolic Disorders (including obesity)