Treatment of Pulmonary Hypertension Due to Left Heart Failure with PAH-Specific Therapies: Lessons from the Right and LEPHT
It has been axiomatic since the early clinical trials with epoprostenol 1,2 that drugs having efficacy treating Pulmonary Arterial Hypertension (PAH) have no clear beneficial effects in treating Pulmonary Hypertension due to left-sided heart disease, and may actually be deleterious. While dysfunction of the three major endothelial-derived pathways targeted by currently approved PAH therapies- the endothelin, nitric oxide, and prostacyclin pathways- is also present in pulmonary hypertension due to left-sided heart disease, their role in the pathogenesis of pulmonary vasculopathy in this setting remains unclear.
Riociguat is a novel molecular entity that acts as a soluble guanylate cyclase activator, thereby directly producing vasodilation, as well as stimulating endogenous nitric oxide-mediated vasodilation. Riociguat is currently undergoing regulatory review for the indications of Pulmonary Arterial Hypertension and Inoperable Chronic Thromboembolic Pulmonary Hypertension (CTEPH), based on the PATENT and CHEST clinical trials, respectively.3,4 In these trials, treatment with riociguat improved 6-minute walking distance (the primary endpoint) and several secondary endpoints compared to placebo, and appeared to be safe and well-tolerated. If approved, riociguat would be the first drug approved for inoperable CTEPH and would join the ranks of other oral therapies for PAH.
- Received June 10, 2013.
- Accepted June 11, 2013.