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.