Cinaciguat (BAY 58 -2667) Improves Cardiopulmonary Hemodynamics in Patients With Acute Decompensated Heart Failure

Background-Cinaciguat (BAY 58 -2667) is the first of a new class of soluble guanylate cyclase activators in clinical development for acute decompensated heart failure. We aimed to assess the hemodynamic effects, safety, and tolerability of intravenous cinaciguat in patients with acute decompensated heart failure (pulmonary capillary wedge pressure Ն18 mm Hg). Methods and Results-After initial dose finding (part A; nϭ27), cinaciguat was evaluated in the nonrandomized, uncontrolled proof-of-concept part of the study (part B; nϭ33) using a starting dose of 100 g/h, which could be titrated depending on hemodynamic response. Patients were categorized as responders if their pulmonary capillary wedge pressure decreased by Ն4 mm Hg compared with baseline. Final doses of cinaciguat after 6 hours of infusion in part B were 50 g/h (nϭ2), 200 g/h (nϭ12), and 400 g/h (nϭ16). Compared with baseline, a 6-hour infusion of cinaciguat led to significant reductions in pulmonary capillary wedge pressure (Ϫ7.9 mm Hg), mean right atrial pressure (Ϫ2.9 mm Hg), mean pulmonary artery pressure (Ϫ6.5 mm Hg), pulmonary vascular resistance (Ϫ43.4 dynes · s · cm Ϫ5 ), and systemic vascular resistance (Ϫ597 dynes · s · cm Ϫ5 ), while increasing heart rate by 4.4 bpm and cardiac output by 1.68 L/min. The responder rate was 53% after 2 hours, 83% after 4 hours, and 90% after 6 hours. Cinaciguat was well tolerated, with 13 of 60 patients reporting 14 drug-related treatment-emergent adverse events of mild to moderate intensity, most commonly hypotension. Conclusions-Cinaciguat has potent preload-and afterload-reducing effects, increasing cardiac output. Further investigation of cinaciguat for acute decompensated heart failure is warranted

BAY 2253651 for the treatment of obstructive sleep apnoea: a multicentre, double-blind, randomised controlled trial (SANDMAN)

BAY 2253651 is a nasally applied genioglossus muscle activator via pharyngeal mucosal receptor stimulation (potassium channel blocker) aimed to treat obstructive sleep apnoea. Although well-tolerated and safe, there was no significant therapeutic effect. https://bit.ly/3zDbyi

Acute Hemodynamic Effects of Riociguat in Patients With Pulmonary Hypertension Associated With Diastolic Heart Failure (DILATE-1)

BACKGROUND: Deficient nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate signaling results from endothelial dysfunction and may underlie impaired cardiac relaxation in patients with heart failure with preserved left ventricular ejection fraction (HFpEF) and pulmonary hypertension (PH). The acute hemodynamic effects of riociguat, a novel soluble guanylate cyclase stimulator, were characterized in patients with PH and HFpEF. METHODS: Clinically stable patients receiving standard HF therapy with a left ventricular ejection fraction. 50%, mean pulmonary artery pressure (mPAP) >= 25 mm Hg, and pulmonary arterial wedge pressure (PAWP). 15 mm Hg at rest were randomized to single oral doses of placebo or riociguat (0.5, 1, or 2 mg). The primary efficacy variable was the peak decrease in mPAP from baseline up to 6 h. Secondary outcomes included hemodynamic and echocardiographic parameters, safety, and pharmacokinetics. RESULTS: There was no significant change in peak decrease in mPAP with riociguat 2 mg (n = 10) vs placebo (n = 11, P = .6). However, riociguat 2 mg significantly increased stroke volume (1 9 mL [95% CI, 0.4-17]; P = .04) and decreased systolic BP (-12 mm Hg [95% CI, -22 to -1]; P = .03) and right ventricular end-diastolic area (-5.6 cm(2) [95% CI, -11 to -0.3]; P = .04), without significantly changing heart rate, PAWP, transpulmonary pressure gradient, or pulmonary vascular resistance. Riociguat was well tolerated. CONCLUSIONS: In patients with HFpEF and PH, riociguat was well tolerated, had no significant effect on mPAP, and improved exploratory hemodynamic and echocardiographic parameters