Riociguatas the first innovative guanylatecyclase stimulators class drugs for pulmonary arterial hypertension patients treatment

Abstract

Pulmonary arterial hypertension (PAH) drug therapy including prostanoids, endothelin receptor antagonists, type 5 phosphodiesterase inhibitors, can improve the possibilities for treatment and control of this progressive and irreversible disease. The modern research vector aims at exploring the potential therapeutic targets, as at developing new drugs that can affect the previously set target. NO synthase production disturbance plays an important role in PAH pathogenesis; this is determined by the powerful vasodylative action, as well as by anti-inflammatory, anti-proliferative, and antiaggregatory effects. Riociguat is the first in a new class of soluble guanylatecyclase stimulators to have proved effective in phase II of clinical trials. In a randomized, double-blind, placebo-controlled phase III of 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 three times a day) or a dose of 1,5 mg (with a dose titration according to portability to 1,5 mg three times a day). The study included patients not previously treated with PAH-specific therapy or those who have already taken endothelin receptor antagonists or prostanoids (except for parenteral ones). The primary endpoint of the PATENT-1 study was the distance dynamics in the 6-minute walk test (D6MH) to 12th treatment week. Secondary endpoints were: the dynamics of pulmonary vascular resistance (PVR), the level of NT-proBNP, functional class (FC) (WHO), the change in the time to developing of clinical deterioration, dyspnea (Borg index), indicators of quality of life and safety. By the 12th riociguat treatment week D6MH hasincreased by an average of 30 m in the group treated with the maximum single dose of 2,5 mg, or has decreased by an average of 6m in the placebo group (difference between groups, 36 m, 95% confidence interval 20–52 m, p