Vascular effects of serelaxin in patients with stable coronary artery disease: a randomized placebo-controlled trial

Corcoran, D. et al. (2021) Vascular effects of serelaxin in patients with stable coronary artery disease: a randomized placebo-controlled trial. Cardiovascular Research, 117(1), pp. 320-329. (doi: 10.1093/cvr/cvz345) (PMID:32065620) (PMCID:PMC7797213)

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Abstract

Aims: The effects of serelaxin, a recombinant form of human relaxin-2 peptide, on vascular function in the coronary microvascular and systemic macrovascular circulation remain largely unknown. This mechanistic, clinical study assessed the effects of serelaxin on myocardial perfusion, aortic stiffness, and safety in patients with stable coronary artery disease (CAD). Methods and results: In this multicentre, double-blind, parallel-group, placebo-controlled study, 58 patients were randomized 1:1 to 48 h intravenous infusion of serelaxin (30 µg/kg/day) or matching placebo. The primary endpoints were change from baseline to 47 h post-initiation of the infusion in global myocardial perfusion reserve (MPR) assessed using adenosine stress perfusion cardiac magnetic resonance imaging, and applanation tonometry-derived augmentation index (AIx). Secondary endpoints were: change from baseline in AIx and pulse wave velocity, assessed at 47 h, Day 30, and Day 180; aortic distensibility at 47 h; pharmacokinetics and safety. Exploratory endpoints were the effect on cardiorenal biomarkers [N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hsTnT), endothelin-1, and cystatin C]. Of 58 patients, 51 were included in the primary analysis (serelaxin, n = 25; placebo, n = 26). After 2 and 6 h of serelaxin infusion, mean placebo-corrected blood pressure reductions of −9.6 mmHg (P = 0.01) and −13.5 mmHg (P = 0.0003) for systolic blood pressure and −5.2 mmHg (P = 0.02) and −8.4 mmHg (P = 0.001) for diastolic blood pressure occurred. There were no between-group differences from baseline to 47 h in global MPR (−0.24 vs. −0.13, P = 0.44) or AIx (3.49% vs. 0.04%, P = 0.21) with serelaxin compared with placebo. Endothelin-1 and cystatin C levels decreased from baseline in the serelaxin group, and there were no clinically relevant changes observed with serelaxin for NT-proBNP or hsTnT. Similar numbers of serious adverse events were observed in both groups (serelaxin, n = 5; placebo, n = 7) to 180-day follow-up. Conclusion: In patients with stable CAD, 48 h intravenous serelaxin reduced blood pressure but did not alter myocardial perfusion.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Berry, Professor Colin and Corcoran, Dr David and Mordi, Dr Ify and Radjenovic, Dr Aleksandra
Authors: Corcoran, D., Radjenovic, A., Mordi, I., Nazir, S. A., Wilson, S. J., Hinder, M., Yates, D. P., Machineni, S., Alcantara, J., Prescott, M. F., Gugliotta, B., Pang, Y., Tzemos, N., Semple, S. I., Newby, D. E., McCann, G. P., Squire, I., and Berry, C.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Cardiovascular Research
Publisher:Oxford University Press
ISSN:0008-6363
ISSN (Online):1755-3245
Published Online:17 February 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Cardiovascular Research 117(1): 320-329
Publisher Policy:Reproduced under a Creative Commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
190721Microvascular Dysfunction in Patients with Angina: The CE-MARC2 Microvascular SubstudyColin BerryBritish Heart Foundation (BHF)FS/14/15/30661Institute of Cardiovascular & Medical Sciences
190721Microvascular Dysfunction in Patients with Angina: The CE-MARC2 Microvascular SubstudyColin BerryBritish Heart Foundation (BHF)FS/14/15/30661Institute of Cardiovascular & Medical Sciences