Evaluation of the pharmacoDYNAMIC effects of riociguat in subjects with pulmonary hypertension and heart failure with preserved ejection fraction

Background The presence of pulmonary hypertension (PH) severely aggravates the clinical course of heart failure with preserved ejection fraction (HFPEF) resulting in substantial morbidity and mortality. So far, neither established heart failure therapies nor pulmonary vasodilators have proven to be effective for this condition. Riociguat (Adempas®, BAY 63-2521), a stimulator of soluble guanylate cyclase, is a novel pulmonary and systemic vasodilator that has been approved for the treatment of precapillary forms of PH. With regard to postcapillary PH, the DILATE-1 study was a multicenter, double-blind, randomized, placebo-controlled single-dose study in subjects with PH associated with HFPEF. Although there was no significant change in the primary outcome measure, peak decrease in mean pulmonary artery pressure with riociguat versus placebo, riociguat significantly increased stroke volume without changing heart rate, pulmonary artery wedge pressure, transpulmonary pressure gradient or pulmonary vascular resistance. The present study is designed to test the efficacy of long-term treatment with riociguat in patients with PH associated with HFPEF.