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

Leopoldo Pérez de Isla, Kausik K. Ray, Gerald F. Watts, Raul D. Santos, Rodrigo Alonso, Ovidio Muñiz-Grijalvo, Jose Luis Diaz-Diaz, Lina Badimon, Alberico L. Catapano, Pedro Mata

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)40-45
Number of pages6
JournalAtherosclerosis
Volume286
DOIs
Publication statusPublished - 1 Jul 2019

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Hyperlipoproteinemia Type II
Monoclonal Antibodies
LDL Cholesterol
Numbers Needed To Treat
Therapeutics
Cholesterol
Proprotein Convertase 9
Consensus
Lipids
Costs and Cost Analysis

Cite this

Pérez de Isla, Leopoldo ; Ray, Kausik K. ; Watts, Gerald F. ; Santos, Raul D. ; Alonso, Rodrigo ; Muñiz-Grijalvo, Ovidio ; Diaz-Diaz, Jose Luis ; Badimon, Lina ; Catapano, Alberico L. ; Mata, Pedro. / Potential utility of the SAFEHEART risk equation for rationalising the use of PCSK9 monoclonal antibodies in adults with heterozygous familial hypercholesterolemia. In: Atherosclerosis. 2019 ; Vol. 286. pp. 40-45.
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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.",
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Potential utility of the SAFEHEART risk equation for rationalising the use of PCSK9 monoclonal antibodies in adults with heterozygous familial hypercholesterolemia. / Pérez de Isla, Leopoldo; Ray, Kausik K.; Watts, Gerald F.; Santos, Raul D.; Alonso, Rodrigo; Muñiz-Grijalvo, Ovidio; Diaz-Diaz, Jose Luis; Badimon, Lina; Catapano, Alberico L.; Mata, Pedro.

In: Atherosclerosis, Vol. 286, 01.07.2019, p. 40-45.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Potential utility of the SAFEHEART risk equation for rationalising the use of PCSK9 monoclonal antibodies in adults with heterozygous familial hypercholesterolemia

AU - Pérez de Isla, Leopoldo

AU - Ray, Kausik K.

AU - Watts, Gerald F.

AU - Santos, Raul D.

AU - Alonso, Rodrigo

AU - Muñiz-Grijalvo, Ovidio

AU - Diaz-Diaz, Jose Luis

AU - Badimon, Lina

AU - Catapano, Alberico L.

AU - Mata, Pedro

PY - 2019/7/1

Y1 - 2019/7/1

N2 - 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.

AB - 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.

KW - Cardiovascular risk assessment

KW - CTT

KW - Familial hypercholesterolemia

KW - NNT

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U2 - 10.1016/j.atherosclerosis.2019.05.003

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