Potential utility of the SAFEHEART risk equation for rationalising the use of PCSK9 monoclonal antibodies in adults with heterozygous familial hypercholesterolemia
File(s)
Accepted version
Author(s)
Type
Journal Article
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.
Date Issued
2019-07
Date Acceptance
2019-05-03
Citation
Atherosclerosis, 2019, 286, pp.40-45
ISSN
0021-9150
Publisher
Elsevier
Start Page
40
End Page
45
Journal / Book Title
Atherosclerosis
Volume
286
Copyright Statement
© 2019 Published by Elsevier B.V. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/31100618
PII: S0021-9150(19)30408-3
Subjects
CTT
Cardiovascular risk assessment
Familial hypercholesterolemia
NNT
PCSK9 mAb
SAFEHEART
Publication Status
Published
Coverage Spatial
Ireland
Date Publish Online
2019-05-04