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. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01065454.
journal_name
Circulationjournal_title
Circulationauthors
Bonderman D,Ghio S,Felix SB,Ghofrani HA,Michelakis E,Mitrovic V,Oudiz RJ,Boateng F,Scalise AV,Roessig L,Semigran MJ,Left Ventricular Systolic Dysfunction Associated With Pulmonary Hypertension Riociguat Trial (LEPHT) Study Group.doi
10.1161/CIRCULATIONAHA.113.001458subject
Has Abstractpub_date
2013-07-30 00:00:00pages
502-11issue
5eissn
0009-7322issn
1524-4539pii
CIRCULATIONAHA.113.001458journal_volume
128pub_type
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