Treatment of Pulmonary Hypertension Caused by Left Heart Failure With Pulmonary Arterial Hypertension–Specific Therapies

Abstract

It has been axiomatic since the early clinical trials with epoprostenol1,2 that drugs having efficacy treating pulmonary arterial hypertension (PAH) have no clear beneficial effects in treating pulmonary hypertension caused by left-sided heart disease and may actually be deleterious. Although dysfunction of the 3 major endothelium-derived pathways targeted by currently approved PAH therapies—the endothelin, nitric oxide, and prostacyclin pathways—is also present in pulmonary hypertension resulting from left-sided heart disease, their role in the pathogenesis of pulmonary vasculopathy in this setting remains unclear. Article see p 502 Riociguat is a novel molecular entity that acts as a soluble guanylate cyclase activator, thereby directly producing vasodilation and stimulating endogenous nitric oxide–mediated vasodilation. Riociguat is currently undergoing regulatory review for the indications of PAH and inoperable chronic thromboembolic pulmonary hypertension on the basis of the Pulmonary Arterial Hypertension sGC-Stimulator Trial and Chronic Thromboembolic Pulmonary Hypertension sGC-Stimulator Trial, respectively.3,4 In these trials, treatment with riociguat improved 6-minute walking distance (the primary end point) and several secondary end points compared with placebo and appeared to be safe and well tolerated. If approved, riociguat would be the first drug approved for inoperable chronic thromboembolic pulmonary hypertension and would join the ranks of other oral therapies for PAH. In this issue of Circulation , Bonderman and colleagues5 report the results of the Left Ventricular Systolic Dysfunction Associated With PH Riociguat Trial (LEPHT), in which they evaluated the effects of riociguat in subjects with pulmonary hypertension caused by left ventricular systolic dysfunction that persisted despite maximal conventional therapy. They enrolled 202 subjects who …