OBJECTIVES : Heterozygous familial hypercholesterolemia (heFH) is an under-diagnosed genetic disorder that leads to premature cardiovascular disease and mortality. Treatments have been shown to be highly effective, but fewer than 20% of US heFH cases are diagnosed and fewer than 50% of US adults receive treatment for high cholesterol. Previous studies have found that genetic screening for heFH with statin treatment is not cost-effective in the US. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) were approved in the US in 2015 for treatment in heFH individuals. Since 2015, the cost of genetic testing has decreased by more than 10-fold. This study aimed to reevaluate the cost-effectiveness of genetic screening and lipid-based screening with intensive therapy (statin + PCSK9i treatment) compared to lipid-based screening (statin treatment alone) in the US.

METHODS : A decision tree was used to estimate disease detection with the three screening strategies, while a Markov model was used to model disease progression until death, quality-adjusted life years (QALYs) and costs from a US societal perspective.

RESULTS : The incremental cost-effectiveness ratio (ICER) of genetic screening with intensive therapy versus lipid screening was $46,471/QALY and that of genetic screening with intensive therapy versus lipid screening with intensive therapy was $35,175/QALY. At a US willingness-to-pay threshold of $150,000/QALY genetic screening and intensive therapy are cost-effective options compared with lipid screening.

CONCLUSIONS : Falling screening costs and falling prices for newly available treatments have permitted genetic testing and intensive therapy to become cost-effective options for individuals with heFH in the US. Efforts and resources may be directed towards increased screening and improved adherence to cholesterol-lowering treatments to improve health outcomes.