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

Herzzentrum der Universität zu Köln, Cologne, Germany. erland.erdmann@uni-koeln.de

European heart journal 2013 Jan

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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). 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. Cinaciguat unloaded the heart in patients with ADHF. However, high doses were associated with hypotension.

Citation

Erland Erdmann, Marc J Semigran, Markku S Nieminen, Mihai Gheorghiade, Rahul Agrawal, Veselin Mitrovic, Alexandre Mebazaa. Cinaciguat, a soluble guanylate cyclase activator, unloads the heart but also causes hypotension in acute decompensated heart failure. European heart journal. 2013 Jan;34(1):57-67