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

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 RESULTS:

In 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.

• Authors: Erland Erdmann, Marc J Semigran, Markku S Nieminen, Mihai Gheorghiade, Rahul Agrawal, Veselin Mitrovic, Alexandre Mebazaa
• Journal: European heart journal (Eur Heart J) Vol. 34 Issue 1 Pg. 57-67 (Jan 2013) ISSN: 1522-9645 [Electronic] England
• PMID: 22778174 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Benzoates
• Guanylate Cyclase-Activating Proteins
• BAY 58-2667

Topics

• Acute Disease
• Benzoates (administration & dosage, adverse effects)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Early Termination of Clinical Trials
• Female
• Glomerular Filtration Rate (drug effects)
• Guanylate Cyclase-Activating Proteins (administration & dosage, adverse effects)
• Heart Failure (drug therapy, physiopathology)
• Hemodynamics (drug effects)
• Humans
• Hypotension (chemically induced, physiopathology)
• Infusions, Intravenous
• Male
• Middle Aged
• Tachycardia, Ventricular (chemically induced)
• Treatment Outcome