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 ( Adempas ), a novel soluble guanylate cyclase stimulator, were characterized in patients with pulmonary hypertension and heart failure with preserved left ventricular ejection fraction.
Clinically stable patients receiving standard heart failure therapy with a left ventricular ejection fraction more than 50%, mean pulmonary artery pressure ( mPAP ) greater than or equal to 25 mm Hg, and pulmonary arterial wedge pressure ( PAWP ) more than 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.
There was no significant change in peak decrease in mPAP with Riociguat 2 mg ( n=10 ) vs placebo ( n=11, P=0.6 ).
However, Riociguat 2 mg significantly increased stroke volume ( +9 mL [ 95% CI, 0.4-17 ]; P = 0.04 ) and decreased systolic blood pressure ( -12 mm Hg [ 95% CI, -22 to -1 ]; P=0.03 ) and right ventricular end-diastolic area ( -5.6 cm2 [ 95% CI, -11 to -0.3 ]; P=0.04 ), without significantly changing heart rate, PAWP, transpulmonary pressure gradient, or pulmonary vascular resistance.
Riociguat was well tolerated.
In conclusion, in patients with heart failure with preserved left ventricular ejection fraction and pulmonary hypertension, Riociguat was well tolerated, had no significant effect on mean pulmonary artery pressure, and improved exploratory hemodynamic and echocardiographic parameters. ( Xagena )
Bonderman D et al, Chest 2014;146:1274-1285