The cost-effectiveness of fixed-dose combinations for preventive cardiovascular pharmacotherapy

Background: Pharmaceutical non-adherence as a consequence of large pill burdens is a noted issue in the management of cardiovascular disease risk (CVD), particularly for populations with high CVD risk or with coexisting comorbidities. Non-adherence to pharmaceuticals means the intended health benefit of the pharmaceutical is not realised and the targeted risk factor remains inadequately controlled. Fixed-dose combinations (FDCs) pharmaceuticals that combine one or more active compounds into a single pill are one method of reducing pill burdens. A body of literature illustrates that CVD FDC pharmacotherapy improves adherence and risk factor control, resulting in a reduction of CVD events and health system savings. Given this background, this thesis aimed to determine if switching individuals from monotherapies (an anti-hypertensive: amlodipine; and a statin: atorvastatin, [A+A]) to an equivalent FDC (amlodipine with atorvastatin, [FDC AA]) would be a health generating and cost-effective intervention for the primary prevention of CVD in the New Zealand context. Methods: Key parameters were identified in literature searches and meta-analyses were performed to determine the clinical efficacy for the FDC AA. An existing CVD multi-state life-table Markov model created by the BODE3 Research Group using rich New Zealand longitudinal data was adapted to model the effect of switching from A+A to the FDC AA in a population of New Zealand men aged 60 to 64 in 2011. The two disease life-tables (stroke and coronary heart disease) were age, sex, and ethnicity-specific (Māori and non-Māori). The model population was separated into five-year strata of absolute CVD risk (0:≤5%, >5:≤10%, >10:≤15%, >15:≤20%, >20%). The intervention period was five years. Initial uptake was the same for both regimens, but adherence and clinical efficacy were greater for FDC AA than the A+A regimen (based on the literature). The medication adherent population received the risk reduction benefits and therefore had lower CVD incidence within each risk stratum. Health system costs and quality-adjusted life-years (QALYs) were accrued over a lifetime horizon and discounted at 3% annually (with variation in sensitivity and scenario analyses). Results: This was the first study to consider the cost-effectiveness of a CVD FDC in New Zealand and the first internationally to assess a CVD FDC by strata of CVD risk. Overall and within each of the CVD risk stratum, the use of the FDC AA resulted in additional QALY gains and additional cost-offsets (net cost-savings) compared to the use of A+A (albeit not significantly for costs). The incremental cost-effectiveness ratio (ICER) in favour of switching to the FDC AA from A+A across all CVD risk strata ranged from cost-saving to $3,570 per QALY gained (or 280 QALYs per million dollars spent for the latter) at the upper bound of the 95% uncertainty interval (95%UI). The absolute QALYs gained and the cost-offsets (savings) were greatest in the lowest CVD risk strata (0:≤5%) with regimen switching resulting in an additional 167 QALYs gained and NZ$ 3.41 million in cost-offsets (savings). The total QALYs gained and cost-offsets (savings) from regimen switching, decreased as CVD risk increased. But the per capita results suggested that individuals with the highest CVD risk, benefited the most from switching to the FCD AA regimen. Conclusions: This work provides modelling-level evidence that replacing the use of two monotherapies with a fixed-dose combination (a statin and anti-hypertensive) appears to be a cost-saving to very cost-effective intervention for the primary prevention of CVD in New Zealand. Further research in other age/sex groups and with other types of CVD FDCs is required to increase the generalisability of these results. The results of this thesis provide strong support for health authorities in high-income countries, such as New Zealand, to consider the inclusion of such FDCs in CVD prevention guidelines, placing a higher value on reducing pill burdens and improving adherence. If such FDCs are not available, then regulatory authorities could solicit the pharmaceutical industry to apply for such products to be registered in their jurisdictions