Early lowering of LDL-C is a more cost-effective strategy than lowering LDL-C later in life: a cost-effectiveness analysis using Mendelian Randomisation

Abstract Background Early control of low-density lipoprotein-cholesterol (LDL-C) is an effective way to reduce the risk of coronary heart disease (CHD). However, a comprehensive assessment of cost-effectiveness of different lipid-lowering strategies (LLS) for primary prevention of CHD across different ages is lacking. Objective To assess the cost-effectiveness of four different LLS initiated at ages 30, 40, 50, and 60 years on the primary prevention of CHD from the UK National Health Service perspective. Design, setting and participants: We developed a microsimulation model, based on the causal effect of LDL-C on myocardial infarction (MI) or coronary death derived from Mendelian randomisation, comparing initiation of an LLS to current standard of care (control). Data were primarily drawn from 458,727 participants of the UK Biobank study with available data on date of birth, LDL-C, and who were free of MI at first assessment (between 2006 and 2010), with follow-up until 2021. Interventions: The four LLS were: 1) low/moderate intensity statins; 2) high intensity statins; 3) low/moderate intensity statins and ezetimibe; and 4) inclisiran. Main outcomes measures: The incremental cost-effectiveness ratio (ICER), defined as the incremental healthcare costs divided by the incremental quality-adjusted life years (QALYs) for each LLS compared to control, with 3.5% annual discounting. Results The most effective intervention, low/moderate intensity statins and ezetimibe, was projected to lead to a gain in QALYs of 0.068 per person at age 30 and 0.026 at age 60 compared to control (Figure). The age of intervention with the lowest ICER was age 40, with ICERs of £2,524 (95% uncertainty interval: 1,383, 3,796), £4,466 (3,163, 6,134) £11,118 (8,632, 14,177), and £1,405,123 (1,117,1113, 1,789,012) per QALY gained for strategies 1-4 from age 40 years, respectively (Table). Conclusions LDL-C lowering from early ages is a more cost-effective strategy than late intervention. The approach to primary prevention of CHD may improve with a shift to early and sustained lowering of LDL-C. Figure – Results of 1,000 probabilistic sensitivity analyses presented in a common cost-effectiveness plane, by age of intervention. Inclisiran excluded due to very high costs. Solid line: £20,000 per quality-adjusted life year (QALY) willingness-to-pay threshold; dashed line: £30,000 per QALY willingness-to-pay threshold. Any dot to the right of these lines is considered cost-effective. Table – Summary of LLS interventions by age of intervention. Abbreviations: MI – Myocardial infarction; YLL – Years of life lived; QALYs – Quality-adjusted life-years; ICER – Incremental cost-effectiveness ratio.FigureTable