A single oral dose of riociguat 2 mg did not significantly change the peak decrease in mean pulmonary artery pressure compared to placebo in patients with HFpEF and PH (P=0.6).
RCT
randomized
Does a single oral dose of riociguat reduce mean pulmonary artery pressure in patients with pulmonary hypertension associated with HFpEF?
A single dose of riociguat did not significantly reduce mean pulmonary artery pressure in patients with PH and HFpEF, but did improve stroke volume and lower systolic blood pressure.
p-value: p=.6
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 (+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 cm2 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. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01172756; URL: www.clinicaltrials.gov.
Bonderman et al. (Thu,) conducted a rct in Heart failure with preserved left ventricular ejection fraction (HFpEF) and pulmonary hypertension (PH). Riociguat vs. Placebo was evaluated on Peak decrease in mPAP from baseline up to 6 h (p=.6). A single oral dose of riociguat 2 mg did not significantly change the peak decrease in mean pulmonary artery pressure compared to placebo in patients with HFpEF and PH (P=0.6).