TY - JOUR
T1 - Vascular effects of serelaxin in patients with stable coronary artery disease
T2 - A randomized placebo-controlled trial
AU - Corcoran, David
AU - Radjenovic, Aleksandra
AU - Mordi, Ify R.
AU - Nazir, Sheraz A.
AU - Wilson, Simon J.
AU - Hinder, Markus
AU - Yates, Denise P.
AU - MacHineni, Surendra
AU - Alcantara, Jose
AU - Prescott, Margaret F.
AU - Gugliotta, Barbara
AU - Pang, Yinuo
AU - Tzemos, Niko
AU - Semple, Scott I.
AU - Newby, David E.
AU - McCann, Gerry P.
AU - Squire, Iain
AU - Berry, Colin
N1 - This study was funded and sponsored by Novartis Pharma AG, Basel, Switzerland. G.P.M was supported by the NIHR (CDF 2014-07-045). CB and DC were supported by the British Heart Foundation (FS/14/15/30661 and RE/18/6134217).
PY - 2021/1/1
Y1 - 2021/1/1
N2 - AimsThe 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 resultsIn 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.ConclusionIn patients with stable CAD, 48 h intravenous serelaxin reduced blood pressure but did not alter myocardial perfusion.
AB - AimsThe 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 resultsIn 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.ConclusionIn patients with stable CAD, 48 h intravenous serelaxin reduced blood pressure but did not alter myocardial perfusion.
KW - Aortic stiffness
KW - Coronary artery disease
KW - Myocardial perfusion
KW - Serelaxin
UR - http://www.scopus.com/inward/record.url?scp=85099721448&partnerID=8YFLogxK
U2 - 10.1093/cvr/cvz345
DO - 10.1093/cvr/cvz345
M3 - Article
C2 - 32065620
AN - SCOPUS:85099721448
SN - 0008-6363
VL - 117
SP - 320
EP - 329
JO - Cardiovascular Research
JF - Cardiovascular Research
IS - 1
ER -
