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

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)epsilon 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 1640 h (starting dose: 100 g/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 epsilon 200 g/h. Cinaciguat unloaded the heart in patients with ADHF. However, high doses were associated with hypotension.