INNOVATION IN PHARMACEUTICAL TREATMENT OF PULMONARY ARTERIAL HYPERTENSION: STIMULATOR OF SOLUBLE GYANYLATE CYCLASE - RIOCIGUAT

• Published in: Evrazijskij kardiologičeskij žurnal (Online) no. 4; pp. 12 - 19
• Main Authors: Taran, I. N., Martynyuk, T. V., Nakonechnikov, S. N., Chazova, I. Ye
• Format: Journal Article
• Language: English
• Published: InterMedservice 30.12.2015
• ISSN: 2225-1685; 2305-0748
• DOI: 10.38109/2225-1685-2015-4-12-19

Pulmonary arterial hypertension (PAH) is a rare disease, diagnosed at a late stage with low functional class III or IV (WHO). PAH leads to severe right heart failure and ultimately, death. The modern researches aim at exploring the potential therapeutic targets, as at developing new drugs that can affect the previously set target. Impaired NO production plays an important role in PAH pathogenesis; this is determined by the powerful vasodilatory action, as well as anti-inflammatory, anti-proliferative, and antiaggregatory effects. Riociguat is the first in a new class of soluble guanylatecyclase stimulators to have proved efficacy in phase II of clinical trials. In the randomized, double-blind, placebo-controlled phase III study PATENT-1 (Pulmonary Arterial Hypertension soluble Guanilatcyclase-Stimulator Trial) study, 443 patients with PAH symptoms were randomized to receive placebo of riociguat in a single dose of 2,5 mg (with a dose titration based on tolerability to 2,5 mg TID a day) or a dose of 1,5 mg (with a dose titration according to portability to 1,5 mg TID three times a day). The study included naïve patients treated with endothelin receptor antagonists or prostanoids (except for parenteral ones). To 12wk of riociguat treatment the mean distance in 6-MWT increased by an average of 30 m in the group treated with the maximum single dose of 2,5 mg TID, or decreased by an average of 6m in the placebo group (difference between groups, 36 m, 95% confidence interval 20-52 m, p p