Blood pressure drops during hospitalization for acute heart failure treated with serelaxin: a patient-level analysis of 4 randomized controlled trials
Abstract
Background: Hypotensive events and drops in systolic blood pressure (SBP-drop) are frequent in patients hospitalized with acute heart failure. We investigated whether SBP-drops are associated with outcomes in patients treated with serelaxin. Methods: Patient-level retrospective analyses of 4 prospective trials investigating serelaxin in acute heart failure. Main inclusion criteria were SBP 125 to 180 mm Hg, pulmonary congestion, and elevated NT-proBNP (N-terminal pro-B-type natriuretic peptide). SBP-drops were prospectively defined as SBP<100 mm Hg, or, if SBP remained >100 mm Hg, a drop from baseline of 40 mm Hg from baseline. Outcomes were a short-term composite outcome (worsening heart failure, hospital readmission for heart failure or all-cause mortality through 14 days) and 180-day mortality. Results: Overall, 2559/11 226 (23%) patients had an SBP-drop. SBP-drop, versus no SBP-drop, was associated with a worse outcome: cumulative incidence of 180-day mortality (11% versus 9%, hazard ratio [HR]. 1.21 [95% CI, 1.05–1.39]; P =0.009) and the short-term outcome (11% versus 9%, HR, 1.29 [95% CI, 1.13–1.49]; P <0.001). Of the 2 SBP-drop components, an SBP<100 mm Hg was associated with the worst outcome compared with a 40 mm Hg drop: short-term outcome (11% versus 10%) and HRs of 1.32 (95% CI, 1.13–1.55; P =0.0005) and 1.22 (95% CI, 0.97–1.56; P =0.09), for each component respectively, with a P value for interaction of 0.05. SBP-drops were associated with a worse short-term outcome in the placebo group (HR, 1.46 [95% CI, 1.19–1.79]; P =0.0003), but not in the serelaxin-group (HR, 1.18 [95% CI, 0.97–1.42]; P =0.10); P interaction=0.003. Conclusions: SBP-drops in patients with acute heart failure and normal to high SBP at admission is associated with worse short- and long-term outcomes especially for SBP <100 mm Hg. However, in patients treated with the intravenous vasodilator serelaxin, SBP-drops seemed less harmful. Registration: URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT02064868, NCT02007720, NCT01870778, NCT00520806.
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Despite the RELAX-AHF trial failure, clinical benefits in haemodynamics and biomarker profile were demonstrated.
“despite the demonstration of clinical benefits in haemodynamics and biomarker profile.4,5”
From Revivifying research on relaxin receptor-targeted therapy for cardiovascular diseases (2025) · cites this paper as [5]
The Conclusions (page unavailable) say that blood-pressure drops appeared less harmful in patients treated with serelaxin than in those receiving usual care or placebo, providing limited support for a haemodynamic benefit. The paper does not demonstrate a benefit in biomarker profile; it uses NT-proBNP in its analyses but does not report an improvement in it with serelaxin. (LLM, conf=0.82)
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- Authors
- Grand, J., Miger, K., Sajadieh, A., Køber, L., Torp-Pedersen, C., Ertl, G., López-Sendón, J., Pietro Maggioni, A., Teerlink, J. R., Sato, N., Gimpelewicz, C., Metra, M., Holbro, T., & Nielsen, O. W.
- Affiliations
- University of Copenhagen (DK)
- Nordsjællands Hospital (DK)
- Universitätsklinikum Würzburg (DE)
- IdiPaz Research Institute, Hospital La Paz, Autonomous University of Madrid, Spain (J.L.-S.).
- Associazione Nazionale Medicin Cardiologi Ospedalieri Research Center, Florence, Italy (A.P.M.).
- San Francisco VA Medical Center (US)
- Department of Cardiovascular Medicine, Kawaguchi Cardiovascular and Respiratory Hospital, Saitama, Japan (N.S.).
- Novartis (Switzerland) (CH)
- Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT)
- ORCID
- Venue
- Circulation: Heart Failure
- Published
- 2022-04
- Volume
- 15
- Issue
- 4
- Pages
- e009199-e009199
- ISSN
- 1941-3289 (ISSN-L)
- 1941-3297
- OpenAlex
- W4213260017
- Cited by
- 6
- References
- 28
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 1 · 2022: 1
- FWCI
- 1.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation Heart Failure (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Hjerteforeningen
- Region Hovedstaden
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
- Keywords
- acute heart failure, hypotension, 180-day mortality, heart failure readmission, NT-proBNP, pulmonary congestion, prognostic factors, randomized controlled trials meta-analysis, individual patient data, treatment effect heterogeneity, prognostic score, natriuretic peptides, vasodilator therapy
- MeSH terms
- Blood Pressure, Heart Failure, Hospitalization, Humans, Hypotension, Prospective Studies, Recombinant Proteins, Relaxin, Retrospective Studies, Vasodilator Agents, Randomized Controlled Trials as Topic, Treatment Outcome
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