Vascular Endothelial Effects of Sacubitril/Valsartan in Heart Failure With Reduced Ejection Fraction: Randomized Controlled Trial.

Autor:	Nägele MP; Cardiology, University Heart Center Zurich, University Hospital Zurich, Zurich, Switzerland., Haider T; Cardiology, University Heart Center Zurich, University Hospital Zurich, Zurich, Switzerland., Kreysing L; Cardiology, University Heart Center Zurich, University Hospital Zurich, Zurich, Switzerland., Barthelmes J; Cardiology, University Heart Center Zurich, University Hospital Zurich, Zurich, Switzerland., Nebunu D; Cardiology, University Heart Center Zurich, University Hospital Zurich, Zurich, Switzerland., Rossi VA; Cardiology, University Heart Center Zurich, University Hospital Zurich, Zurich, Switzerland., Hebeisen M; Department of Biostatistics, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland., Sudano I; Cardiology, University Heart Center Zurich, University Hospital Zurich, Zurich, Switzerland., Ruschitzka F; Cardiology, University Heart Center Zurich, University Hospital Zurich, Zurich, Switzerland., Flammer AJ; Cardiology, University Heart Center Zurich, University Hospital Zurich, Zurich, Switzerland.
Jazyk:	angličtina
Zdroj:	JACC. Advances [JACC Adv] 2024 Nov 13; Vol. 3 (12), pp. 101392. Date of Electronic Publication: 2024 Nov 13 (Print Publication: 2024).
DOI:	10.1016/j.jacadv.2024.101392
Abstrakt:	Background: The mechanism of how sacubitril/valsartan improves outcomes in heart failure with reduced ejection fraction (HFrEF) is still incompletely understood. Objectives: The aim of this trial was to delineate the effects of sacubitril/valsartan on endothelial function, retinal microvascular function, and arterial stiffness in HFrEF. Methods: This double-blind controlled trial randomized 79 stable HFrEF patients with NYHA class II-IV on guideline-recommended therapy (mean age: 59.4 ± 12 years, left ventricular ejection fraction: 30% ± 7%) to sacubitril/valsartan or valsartan alone for 3 months. The primary endpoint was flow-mediated vasodilation (FMD). Secondary outcomes included flicker-induced dilatation of retinal arterioles and venules (FIDv), retinal arteriovenous ratio, and surrogate markers of arterial stiffness (pulse wave velocity and augmentation index). Results: The primary outcome FMD did not significantly differ between sacubitril/valsartan and valsartan alone (FMD 6.6% ± 3.9% vs 6.7% ± 2.8%; ANCOVA coefficient adjusted for baseline values 0.36, 95% CI: -0.78 to 1.51, P  = 0.53). The secondary outcomes flicker-induced dilatation of retinal arterioles, arteriovenous ratio, pulse wave velocity, and augmentation index showed no significant differences. FIDv was lower after sacubitril/valsartan versus valsartan alone (FIDv 2.4% ± 1.3% vs 3.1% ± 2.1%; ANCOVA coefficient -0.7, 95% CI: -1.4 to -0.02, P  = 0.04). Systolic blood pressure was lower after sacubitril/valsartan versus valsartan alone (ANCOVA coefficient -6.5 mm Hg, 95% CI: -12.7 to -0.3 mm Hg, P  = 0.04). There were numerically fewer serious adverse events with sacubitril/valsartan versus valsartan alone. Conclusions: In this randomized double-blind clinical trial addressing mechanisms, sacubitril/valsartan lowered blood pressure and flicker-induced dilatation of retinal venules in patients with symptomatic HFrEF but did not improve endothelial function, retinal microvascular function, or arterial stiffness compared to valsartan monotherapy. (Differential Vascular and Endocrine Effects of Valsartan/​Sacubitril in Heart Failure With Reduced Ejection Fraction [VASCEND]; NCT03168568). Competing Interests: This study was funded by 10.13039/100004336Novartis AG and the 10.13039/501100006447University of Zurich. The funders had no role in the design and conduct of the study, in the collection, analysis, and interpretation of the data, and in the preparation, review, or approval of the manuscript. Dr Nägele has received speaker fees by Vifor Pharma and AstraZeneca; congress travel support by 10.13039/100004319Pfizer; and consultancy fees from Boehringer Ingelheim and Pierre Fabre, all unrelated to this article. Dr Rossi has received congress travel support by 10.13039/100002429Amgen and 10.13039/100004326Bayer, unrelated to the article. Dr Barthelmes has received speaker fees by Imedos Systems; and congress fees by Servier, unrelated to the article. Dr Ruschitzka has not received personal payments by pharmaceutical companies or device manufacturers in the last 3 years (remuneration for the time spent in activities, such as participation as steering committee member of clinical trials and member of the Pfizer Research Award selection committee in Switzerland, were made directly to the University of Zurich). The Department of Cardiology of the University Hospital Zurich has received research-, educational- and/or travel grants from 10.13039/100000046Abbott, 10.13039/100020297Abiomed, 10.13039/100006396Alexion, 10.13039/100002429Amgen, AstraZeneca, At the Limits Ltd, 10.13039/100004326Bayer, Berlin Heart, B. Braun, 10.13039/100007497Biosense Webster, Biosensors Europe AG, 10.13039/501100005035Biotronik, 10.13039/100002491BMS, 10.13039/100001003Boehringer Ingelheim, 10.13039/100008497Boston Scientific, 10.13039/100030777Bracco, Cardinal Health Switzerland, 10.13039/100030895Concept Medical, Corteria, 10.13039/100008322CSL, 10.13039/501100022274Daiichi Sankyo, Diatools AG, 10.13039/100006520Edwards Lifesciences, FomF GmbH, Guidant Europe NV (BS), Hamilton Health Sciences, 10.13039/100001696IHF, 10.13039/501100013348Innosuisse, Johnson/Johnson, Kaneka Corporation, Kantar, 10.13039/100016492Kiniksa, Labormedizinisches Zentrum, 10.13039/501100023518MedAlliance, Medcon International, Medical Education Global Solutions, 10.13039/100004374Medtronic, 10.13039/501100018918MicroPort, Monocle, 10.13039/100007054MSD, 10.13039/100019138Mundipharma Medical Company, 10.13039/100004336Novartis, 10.13039/501100004191Novo Nordisk, 10.13039/501100024580Orion, 10.13039/100004319Pfizer, Quintiles Switzerland Sarl, RecorMedical, 10.13039/100016545Roche Diagnostics, Roche Pharma, Sahajanand IN, 10.13039/100004339Sanofi, Sarstedt AG, 10.13039/501100011725Servier, SIS Medical, Sorin CRM SAS, SSS International Clinical Research, Stromal, Terumo Deutschland, Trama Solutions, V-Wave, Vascular Medical, Vifor, Wissens Plus, ZOLL. These grants do not impact on the personal remuneration of Dr Ruschitzka. Dr Sudano has received consulting fees, travel grant and honoraria from Amgen, AstraZeneca, Daiichi Sankio, Medtronic, MSD, Novartis, Recordati, Sanofi and Servier, all unrelated to the present article. Dr Flammer has received fees from Alnylam, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Fresenius, Imedos Systems, Medtronic, MSD, Mundipharma, Novartis, Pierre Fabre, Pfizer, Roche, Schwabe Pharma. Vifor, and Zoll, all unrelated to this article. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. (© 2024 The Authors.)
Databáze:	MEDLINE
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