BACKGROUND: Approximately 1 in 11 people are intolerant to statins. There have been no studies evaluating the cost-effectiveness of early intervention for primary prevention of cardiovascular disease (CVD) with three non-statin drugs (ezetimibe, proprotein convertase subtilisin-kexin type 9 inhibitors (PCSK9i
inclisiran and evolocumab), and bempedoic acid). We aimed to evaluate the cost-effectiveness of these therapies when initiated at age 40 years. METHODS: We used a published microsimulation model populated with 108 statin-intolerant individuals. The model simulated the ageing of individuals from 40 to 85 years. We calculated the incremental cost-effectiveness ratio (ICER) when non-statin lipid lowering strategies were initiated at age 40 years compared to no intervention until a cardiovascular event. ICERs were compared to Australian and UK cost-effectiveness thresholds of 28,000 AUD and 25,000 GBP per QALY gained, respectively. We adopted each countries national healthcare system perspective (2022 AUD/GBP) and discounted health economic results by 5% annually for Australia and 3.5% annually for the UK. RESULTS: At current prices in Australia, ezetimibe was cost-effective in 34/108 (31.4%) individuals simulated
bempedoic acid in 17/108 (15.7%)
bempedoic acid and ezetimibe in combination in 14/108 (13.0%)
whilst inclisiran and evolocumab were not cost-effective in any individuals. Corresponding numbers for the UK were 98/108 (90.7%)
5/108 (4.6%)
11/108 (10.2%)
0/108 (0.0%)
and 0/108 (0.0%). Cost-effectiveness of bempedoic acid was predominantly among individuals with an LDL-C of at least 4.0 mmol/L and systolic blood pressure of at least 140 mmHg in Australia and 5.0mmol/L and 160 mmHg in the UK, respectively. CONCLUSION: Ezetimibe and bempedoic acid, both alone and in combination, are cost-effective for long-term primary prevention of CVD in a range of people with statin-intolerance, depending on their baseline risk of CVD.