Cinaciguat, a soluble guanylate cyclase activator: results from the randomized, controlled, phase IIb COMPOSE programme in acute heart failure syndromes.

Abstract

AIMS:

Cinaciguat (BAY 58-2667) is a soluble guanylate cyclase (sGC) activator that, in a previous study among patients with acute heart failure syndromes (AHFS), improved pulmonary capillary wedge pressure (PCWP) at the expense of significant hypotension at doses ≥200 µg/h. The aim of the COMPOSE programme was to investigate the safety and efficacy of fixed, low doses of intravenous cinaciguat (<200 µg/h for 24-48 h) as add-on to standard therapy in adults hospitalized with AHFS.

METHODS AND RESULTS:

COMPOSE comprised three randomized, double-blind, placebo-controlled studies in patients with [COMPOSE 1 and 2 (NCT01065077 and NCT01067859)] or without [COMPOSE EARLY (NCT01064037)] a requirement for invasive haemodynamic monitoring. COMPOSE 1 and COMPOSE EARLY assessed the effects of cinaciguat (50, 100, and 150 µg/h) on haemodynamics and dyspnoea, respectively. COMPOSE 2 assessed the haemodynamic effects of 10 and 25 µg/h cinaciguat. COMPOSE was terminated early due to an excess of non-fatal hypotension and recruitment difficulties. In COMPOSE 1 (n = 12), cinaciguat reduced PCWP at 8 h compared with placebo, but there was no relevant change in cardiac index. In COMPOSE EARLY (n = 62), no meaningful difference in dyspnoea was shown between cinaciguat and placebo.

CONCLUSION:

In this limited database, short-term use of intravenous cinaciguat decreased blood pressure without improving dyspnoea or cardiac index. Given the lack of effect on dyspnoea and cardiac index and the hypotensive effect seen even with low doses, it is doubtful that further studies with intravenous cinaciguat would prove beneficial in this patient population.

• Authors: Mihai Gheorghiade, Stephen J Greene, Gerasimos Filippatos, Erland Erdmann, Roberto Ferrari, Phillip D Levy, Aldo Maggioni, Christina Nowack, Alexandre Mebazaa, COMPOSE Investigators and Coordinators
• Journal: European journal of heart failure (Eur J Heart Fail) Vol. 14 Issue 9 Pg. 1056-66 (Sep 2012) ISSN: 1879-0844 [Electronic] England
• PMID: 22713287 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Pharmaceutic
• Benzoates
• BAY 58-2667
• Guanylate Cyclase

Topics

• Acute Disease
• Adjuvants, Pharmaceutic (administration & dosage, adverse effects)
• Aged
• Aged, 80 and over
• Benzoates (administration & dosage, adverse effects)
• Blood Pressure (drug effects)
• Double-Blind Method
• Dyspnea (drug therapy)
• Enzyme Activation
• Female
• Glomerular Filtration Rate (drug effects)
• Guanylate Cyclase (metabolism)
• Heart Failure (drug therapy, physiopathology)
• Hemodynamics (drug effects)
• Humans
• Infusions, Intravenous
• Male
• Middle Aged
• Syndrome