Leopoldo Pérez de Isla1, Kausik K Ray2, Gerald F Watts3, Raul D Santos4, Rodrigo Alonso5, Ovidio Muñiz-Grijalvo6, Jose Luis Diaz-Diaz7, Lina Badimon8, Alberico L Catapano9, Pedro Mata10. 1. Cardiology Department, Hospital Clínico San Carlos, IDISSC, Universidad Complutense, Madrid, Spain; Fundación Hipercolesterolemia Familiar, Madrid, Spain. Electronic address: leopisla@hotmail.com. 2. Imperial Centre for Cardiovascular Disease Prevention, Department of primary Care and Public Health, Imperial College London, London, UK. 3. School of Medicine, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Australia; Lipid Disorders Clinic, Department of Cardiology, Royal Perth Hospital, Perth, Australia. 4. Heart Institute (InCor) University of Sao Paulo Medical School Hospital, Sao Paulo, Brazil; Hospital Israelita Albert Einstein, Sao Paulo, Brazil. 5. Clínica las Condes, Santiago de Chile, Chile. 6. Department of Internal Medicine, Hospital Virgen del Rocío, Sevilla, Spain. 7. Department of Internal Medicine, Hospital Abente y Lago, A Coruña, Spain. 8. Cardiovascular program-ICCC, IR-Hospital de la Santa Creu i Sant Pau, CiberCV, Barcelona, Spain. 9. Department of Pharmacological and Biomolecular Sciences, University of Milan and MultiMedica IRCCS, Milano, Italy. 10. Fundación Hipercolesterolemia Familiar, Madrid, Spain. Electronic address: pmata@colesterolfamiliar.org.
Abstract
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.
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 FHpatients 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 FHpatients who might derive greater absolute benefits from PCSK9 mAb.
Authors: Gerald F Watts; Samuel S Gidding; Pedro Mata; Jing Pang; David R Sullivan; Shizuya Yamashita; Frederick J Raal; Raul D Santos; Kausik K Ray Journal: Nat Rev Cardiol Date: 2020-01-23 Impact factor: 32.419