Effects of sacubitril/valsartan on serum lipids in heart failure with preserved ejection fraction

Selvaraj, S. et al. (2021) Effects of sacubitril/valsartan on serum lipids in heart failure with preserved ejection fraction. Journal of the American Heart Association, 10(17), e022069. (doi: 10.1161/JAHA.121.022069) (PMID:33998278) (PMCID:PMC8649234)

Abstract

Background: Dyslipidemia is common in heart failure with preserved ejection fraction. Sacubitril/valsartan improves glycemic control and augments natriuretic peptide signaling, providing mechanisms by which sacubitril/valsartan may affect serum lipids. However, empiric data on these effects are lacking. Methods and Results: We analyzed 4774 participants from PARAGON‐HF (Prospective Comparison of Angiotensin Receptor–Neprilysin Inhibitor With Angiotensin‐Receptor Blockers Global Outcomes in Heart Failure With Preserved Ejection Fraction) with available screening lipids. During follow‐up visits, we analyzed the treatment effect on lipid levels and assessed for interaction by baseline lipid levels. At the 16‐week visit, we adjusted these treatment effects for the change in several biomarkers (including hemoglobin A1c and urinary cyclic guanosine monophosphate/creatinine [a biomarker of natriuretic peptide activation]). The average age was 73±8 years, 52% were women, 43% had diabetes mellitus, and 64% were on statin therapy. Compared with valsartan, sacubitril/valsartan reduced triglycerides −5.0% (95% CI, −6.6% to −3.5%), increased high‐density lipoprotein cholesterol +2.6% (95% CI, +1.7% to +3.4%), and increased low‐density lipoprotein cholesterol +1.7% (95% CI, +0.4% to +3.0%). Sacubitril/valsartan reduced triglycerides most among those with elevated baseline levels (triglycerides≥200 mg/dL) (P‐interaction<0.001), and at 16 weeks by −13.0% (95% CI, −18.1% to −7.6%), or −29.9 (95% CI, −44.3 to −15.5) mg/dL, in this group. Adjusting for the change in urinary cyclic guanosine monophosphate/creatinine significantly attenuated treatment effects on triglycerides and high‐density lipoprotein cholesterol, but not low‐density lipoprotein cholesterol, while adjusting for other biomarkers did not significantly alter the treatment effects. Conclusions: Sacubitril/valsartan significantly reduces triglycerides compared with valsartan, an effect that was nearly threefold stronger in those with elevated baseline triglycerides. Modest increases in high‐density lipoprotein cholesterol and low‐density lipoprotein cholesterol cholesterol were also observed with therapy. The underlying mechanism(s) of changes in high‐density lipoprotein cholesterol and triglycerides are related to sacubitril/valsartan’s effects on natriuretic peptide activity. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920711.

• Item Type: Articles
• Additional Information: PARAGON-HF was funded by Novartis.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McMurray, Professor John
• Authors: Selvaraj, S., Claggett, B. L., Packer, M., Zannad, F., Anand, I. S., Pieske, B., Zhao, Z., Shi, V. C., Lefkowitz, M. P., McMurray, J. J.V., and Solomon, S. D.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Journal of the American Heart Association
• Publisher: American Heart Association
• ISSN: 2047-9980
• ISSN (Online): 2047-9980
• Published Online: 16 May 2021
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Journal of the American Heart Association 10(17): e022069
• Publisher Policy: Reproduced under a Creative Commons License