Rethinking cardiovascular prevention: cost-effective cholesterol lowering for statin-intolerant patients in Australia and the UK

Aims: 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 and results: 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 when non-statin lipid-lowering strategies were initiated at age 40 years compared to no intervention until a cardiovascular event. Incremental cost-effectiveness ratios were compared to Australian and UK cost-effectiveness thresholds of 28 000 AUD and 25 000 GBP per quality adjusted life year 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. 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%); while 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 5.0 mmol/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. Approximately 1 in 11 people are intolerant to the main drug used to lower cholesterol, statins, but there have not been any studies looking at the cost-effectiveness of the drugs available to treat people who can't take statins. We assessed the cost-effectiveness of five strategies to lower cholesterol in Australia and the UK. We found: The lifetime risk of having a heart attack or stroke is much lower when therapy is initiated early in life compared to not at all. Lots of people could benefit (in a cost-effective way) from the drugs we tested, including the new drug known as bempedoic acid.