Potential utility of the SAFEHEART risk equation for rationalising the use of PCSK9 monoclonal antibodies in adults with heterozygous familial hypercholesterolemia

Background and aims: Patients with familial hypercholesterolaemia (FH)may require proprotein convertase subtilisin/kexin-type 9 (PCSK9)mAb as add-on therapy to achieve LDL-cholesterol (LDL-C)goals. However, the current cost of these therapies means that choosing suitable patients is based on consensus or clinical judgement rather than a quantitative risk assessment. We used the SAFEHEART Risk Equation (RE)to estimate the number needed to treat (NNT)at different risk thresholds and baseline LDL-C to identify those FH patients more likely to derive the greatest benefit from PCSK9 mAb. Methods: Five-year event rates were calculated using the SAFEHEART-RE for every patient, overall and across LDL-C strata. A 60% reduction of LDL-C after theoretical treatment with PCSK9 mAb was assumed. Individual absolute risk simulating the effects of PCSK9 inhibition was calculated using the SAFEHEART-RE and, in a similar way, by using the Cholesterol Treatment Trialists’ (CTT)Collaboration criteria. Absolute risk reduction and NNTs were calculated. Results: Of the total SAFEHEART population, 2,153 were FH cases aged 18 years or older, on maximum tolerated lipid lowering treatment. NNTs were dependent of both baseline predicted risk and baseline LDL-C level ranging from 44 to 17 for those with 5-year risk of ≥1 to ≥5. The smallest NNT (12)was observed among those with 5-year risk of ≥5% and LDL-C ≥160 mg/dl. Using the CTT criteria produced similar results. Conclusions: The SAFEHEART-RE may provide a useful quantitative tool for rationalising the selection of FH patients who might derive greater absolute benefits from PCSK9 mAb.