Journalartikel

Jahr der Veröffentlichung: 2013

Seiten: 502-U95

Zeitschrift: Circulation

Bandnummer: 128

Heftnummer: 5

ISSN: 0009-7322

eISSN: 1524-4539

Open Access Status: Bronze

DOI Link: https://doi.org/10.1161/CIRCULATIONAHA.113.001458

Verlag: Lippincott, Williams & Wilkins

Abstract: 

Background-Pulmonary hypertension caused by systolic left ventricular dysfunction is associated with significant morbidity and mortality; however, no treatment is approved for this indication. We hypothesized that riociguat, a novel soluble guanylate cyclase stimulator, would have beneficial hemodynamic effects in patients with pulmonary hypertension caused by systolic left ventricular dysfunction.

Methods and Results-Overall, 201 patients with heart failure resulting from pulmonary hypertension caused by systolic left ventricular dysfunction were randomized to double-blind treatment with oral placebo or riociguat (0.5, 1, or 2 mg 3 times daily) for 16 weeks in 4 parallel arms. The primary outcome was the placebo-corrected change from baseline at week 16 in mean pulmonary artery pressure. Although the decrease in mean pulmonary artery pressure in the riociguat 2 mg group (-6.1+/-1.3 mm Hg; P<0.0001 versus baseline) was not significantly different from placebo (P=0.10), cardiac index (0.4 L.min(-1).m(-2); 95% confidence interval, 0.2-0.5; P=0.0001) and stroke volume index (5.2 mL.m(-2);95% confidence interval, 2.0-8.4; P=0.0018) were significantly increased without changes in heart rate or systemic blood pressure compared with placebo. Both pulmonary (-46.6 dynes.s(-1).cm(-5); 95% confidence interval, -89.4 to -3.8; P=0.03) and systemic vascular resistance (-239.3 dynes.s(-1).cm(-5); 95% confidence interval, -363.4 to -115.3; P=0.0002) were significantly reduced with riociguat 2 mg. Riociguat reduced the Minnesota Living With Heart Failure score (P=0.0002). Discontinuation of treatment was similar between treatment groups.

Conclusions-Although the primary end point of the study was not met, riociguat was well tolerated in patients with pulmonary hypertension caused by systolic left ventricular dysfunction and improved cardiac index and pulmonary and systemic vascular resistance.

Harvard-Zitierstil: Bonderman, D., Ghio, S., Felix, S., Ghofrani, H., Michelakis, E., Mitrovic, V., et al. (2013) Riociguat for Patients With Pulmonary Hypertension Caused by Systolic Left Ventricular Dysfunction A Phase IIb Double-Blind, Randomized, Placebo-Controlled, Dose-Ranging Hemodynamic Study, Circulation, 128(5), pp. 502-U95. https://doi.org/10.1161/CIRCULATIONAHA.113.001458

APA-Zitierstil: Bonderman, D., Ghio, S., Felix, S., Ghofrani, H., Michelakis, E., Mitrovic, V., Oudiz, R., Boateng, F., Scalise, A., Roessig, L., & Semigran, M. (2013). Riociguat for Patients With Pulmonary Hypertension Caused by Systolic Left Ventricular Dysfunction A Phase IIb Double-Blind, Randomized, Placebo-Controlled, Dose-Ranging Hemodynamic Study. Circulation. 128(5), 502-U95. https://doi.org/10.1161/CIRCULATIONAHA.113.001458