Cinaciguat, a soluble guanylate cyclase activator, unloads the heart but also causes hypotension in acute decompensated heart failure

Erland Erdmann*, Marc J. Semigran, Markku S. Nieminen, Mihai Gheorghiade, Rahul Agrawal, Veselin Mitrovic, Alexandre Mebazaa

*Corresponding author for this work

Research output: Contribution to journalArticle

85 Scopus citations

Abstract

Aims Cinaciguat (BAY 58-2667) is a novel soluble guanylate cyclase activator. This study evaluated the haemodynamic effect and safety of cinaciguat added to standard therapy in patients with acute decompensated heart failure (ADHF).Methods and resultsIn this placebo-controlled, phase IIb study (NCT00559650), 139 patients admitted with ADHF, pulmonary capillary wedge pressure (PCWP) ≥18 mmHg, left ventricular ejection fraction <40%, and a pre-existing need for invasive haemodynamic monitoring were randomized 2:1 to cinaciguat:placebo (continuous i.v. infusion). The dose was titrated for 8 h and maintained for 16-40 h (starting dose: 100 μg/h). At 8 h, mean PCWP changed from 25.7 ± 5.0 mmHg by-7.7 mmHg with cinaciguat and from 25.0 ± 5.3 mmHg by-3.7 mmHg with placebo (P < 0.0001). The mean right atrial pressure changed from 12.4 ± 5.3 mmHg by-2.7 mmHg with cinaciguat and from 11.8 ± 4.9 mmHg by-0.6 mmHg with placebo (P= 0.0019). Cinaciguat also decreased the pulmonary and systemic vascular resistance and the mean arterial pressure, and increased the cardiac index (all P < 0.0001 vs. placebo). Systolic blood pressure changed by-21.6 ± 17.0 mmHg with cinaciguat and-5.0 ± 14.5 mmHg with placebo. Adverse events were experienced by 71 and 45% of patients receiving cinaciguat and placebo, respectively. No adverse effects on the 30-day mortality were seen; however, the trial was stopped prematurely due to an increased occurrence of hypotension at cinaciguat doses ≥200 μg/h. Conclusion Cinaciguat unloaded the heart in patients with ADHF. However, high doses were associated with hypotension.

Original languageEnglish (US)
Pages (from-to)57-67
Number of pages11
JournalEuropean heart journal
Volume34
Issue number1
DOIs
StatePublished - Jan 1 2013

Keywords

  • Cinaciguat
  • Clinical trial, phase 2
  • Haemodynamics
  • Heart failure
  • Soluble guanylyl cyclase
  • Vasodilation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Erdmann, E., Semigran, M. J., Nieminen, M. S., Gheorghiade, M., Agrawal, R., Mitrovic, V., & Mebazaa, A. (2013). Cinaciguat, a soluble guanylate cyclase activator, unloads the heart but also causes hypotension in acute decompensated heart failure. European heart journal, 34(1), 57-67. https://doi.org/10.1093/eurheartj/ehs196