Dataset Information

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

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.

SUBMITTER: Corcoran D

PROVIDER: S-EPMC7797213 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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

Corcoran David D Radjenovic Aleksandra A Mordi Ify R IR Nazir Sheraz A SA Wilson Simon J SJ Hinder Markus M Yates Denise P DP Machineni Surendra S Alcantara Jose J Prescott Margaret F MF Gugliotta Barbara B Pang Yinuo Y Tzemos Niko N Semple Scott I SI Newby David E DE McCann Gerry P GP Squire Iain I Berry Colin C

Cardiovascular research 20210101 1

<h4>Aims</h4>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).<h4>Methods and results</h4>In this multicentre, double-blind, parallel-group, placebo-controlled study, 58 patients were ran ...[more]

PMID: 32065620

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Project description:BackgroundPercutaneous coronary intervention (PCI) is frequently performed to reduce the symptoms of stable angina. Whether PCI relieves angina more than a placebo procedure in patients who are not receiving antianginal medication remains unknown.MethodsWe conducted a double-blind, randomized, placebo-controlled trial of PCI in patients with stable angina. Patients stopped all antianginal medications and underwent a 2-week symptom assessment phase before randomization. Patients were then randomly assigned in a 1:1 ratio to undergo PCI or a placebo procedure and were followed for 12 weeks. The primary end point was the angina symptom score, which was calculated daily on the basis of the number of angina episodes that occurred on a given day, the number of antianginal medications prescribed on that day, and clinical events, including the occurrence of unblinding owing to unacceptable angina or acute coronary syndrome or death. Scores range from 0 to 79, with higher scores indicating worse health status with respect to angina.ResultsA total of 301 patients underwent randomization: 151 to the PCI group and 150 to the placebo group. The mean (±SD) age was 64±9 years, and 79% were men. Ischemia was present in one cardiac territory in 242 patients (80%), in two territories in 52 patients (17%), and in three territories in 7 patients (2%). In the target vessels, the median fractional flow reserve was 0.63 (interquartile range, 0.49 to 0.75), and the median instantaneous wave-free ratio was 0.78 (interquartile range, 0.55 to 0.87). At the 12-week follow-up, the mean angina symptom score was 2.9 in the PCI group and 5.6 in the placebo group (odds ratio, 2.21; 95% confidence interval, 1.41 to 3.47; P<0.001). One patient in the placebo group had unacceptable angina leading to unblinding. Acute coronary syndromes occurred in 4 patients in the PCI group and in 6 patients in the placebo group.ConclusionsAmong patients with stable angina who were receiving little or no antianginal medication and had objective evidence of ischemia, PCI resulted in a lower angina symptom score than a placebo procedure, indicating a better health status with respect to angina. (Funded by the National Institute for Health and Care Research Imperial Biomedical Research Centre and others; ORBITA-2 ClinicalTrials.gov number, NCT03742050.).

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Dataset Information

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

Aims

Methods and results

Conclusion

Publications

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

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