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Effects of Sacubitril/Valsartan on Serum Lipids in Heart Failure with Preserved Ejection Fraction

Abstract : Abstract Background Dyslipidemia is common in heart failure with preserved ejection fraction (HFpEF). Sacubitril/valsartan improves insulin sensitivity and augments natriuretic peptide (NP) signaling, providing mechanisms by which sacubitril/valsartan may affect serum lipids. However, empiric data on these effects are lacking. Methods and Results We analyzed 4,744 participants from PARAGON‐HF 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 (cGMP)/creatinine [a biomarker of NP 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% (‐6.6%, ‐3.5%), increased high‐density lipoprotein cholesterol (HDL‐c) +2.6% (+1.7%, +3.4%), and increased low‐density lipoprotein cholesterol (LDL‐c) +1.7% (+0.4%, +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% (‐18.1%, ‐7.6%), or ‐29.9 (‐44.3, ‐15.5) mg/dL, in this group. Adjusting for the change in urinary cGMP/creatinine significantly attenuated treatment effects on triglycerides and HDL‐c, but not LDL‐c, 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 substantially stronger in those with elevated baseline triglycerides. Modest increases in HDL‐c and LDL‐c cholesterol were also observed with therapy. The underlying mechanism(s) of changes in HDL‐c and triglycerides are related to sacubitril/valsartan’s effects on NP activity.
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Contributor : Erwan BOZEC Connect in order to contact the contributor
Submitted on : Wednesday, May 26, 2021 - 11:00:55 AM
Last modification on : Thursday, December 1, 2022 - 3:56:08 PM
Long-term archiving on: : Friday, August 27, 2021 - 6:52:14 PM


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Senthil Selvaraj, Brian L Claggett, Milton Packer, Faiez Zannad, Inder S Anand, et al.. Effects of Sacubitril/Valsartan on Serum Lipids in Heart Failure with Preserved Ejection Fraction. Journal of the American Heart Association, 2021, pp.e022069. ⟨10.1161/JAHA.121.022069⟩. ⟨hal-03236280⟩



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