Beyond ten-year risk: novel approaches to the primary prevention of cardiovascular disease

In cost-effectiveness analysis, outcomes are typically averaged across large groups to represent a patient population. Implementation and reimbursement decisions based on such analyses often ignore considerable heterogeneity in cost-effectiveness between patients. While good practice guidance for economic evaluations suggest including subgroup analysis, in practice this is frequently overlooked or underutilised. This thesis shows that failing to adequately represent heterogeneity in decision-making leads to an inefficient distribution of healthcare resources. This theory is applied in a study of cholesterol-reducing medication for the primary prevention of cardiovascular disease (CVD). Despite improvements in recent years, CVD remains a significant cause of mortality, morbidity, and health inequality around the world. Rates of the disease have begun to plateau in recent years and novel approaches to its prevention are required. Cholesterol reduction for the primary prevention of cardiovascular disease is a clinical area where better reflection of heterogeneity in cost-effectiveness could significantly improve current practice. Statins are a widely prescribed cholesterol-reducing medication which have recently come off patent. This has led them to become cheaper and cost-effective in a large proportion of CVD-free populations in high-income countries. PCSK9 inhibitors are a more expensive and more effective cholesterol-reducing medication. For both treatments, decision-makers must establish which groups they will prioritise for treatment. Through epidemiologic and health economic analysis, this thesis aims to establish optimal approaches for prioritising patients for cholesterol-reducing therapy. Preventive statin therapy is typically targeted at individuals estimated to have a high ten-year risk of developing CVD. However, individuals with the same ten-year risk may experience different outcomes from preventive treatment. The epidemiologic bases for three alternativ