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

2013 ◽  
Vol 10 (4) ◽  
pp. 70-75
Author(s):  
I E Chazova ◽  
T V Martynyuk
Keyword(s):  
Single Dose ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
New Drugs ◽  
Phase Iii ◽  
Dose Titration ◽  
Endothelin Receptor Antagonists ◽  
Endothelin Receptor ◽  
Receptor Antagonists ◽  
Pulmonary Arterial

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

scholarly journals Pulmonary hypertension: reasonable selection of specific therapy

2018 ◽  
Vol 15 (1) ◽  
pp. 45-50
Author(s):  
N A Karoli ◽  
S I Sazhnova ◽  
A P Rebrov
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Structural Changes ◽  
Pulmonary Arteries ◽  
Endothelin Receptor Antagonists ◽  
Endothelin Receptor ◽  
Receptor Antagonists ◽  
Pulmonary Vasodilator ◽  
Pulmonary Arterial

Pulmonary hypertension is characterized with persistent increase in pulmonary vascular resistance leading to progressive worsening of right ventricular failure and death. The basis for pulmonary arterial hypertension is structural changes in pulmonary arteries and arterioles caused by endothelial dysfunction. Endothelin-1 is the main pathogenic trigger of pulmonary hypertension and potential target for therapeutic exposure. The efficacy of endothelin receptor antagonists is proved in various preclinical and clinical studies. In patients with pulmonary arterial hypertension, the efficacy of dual and selective endothelin receptor antagonists is comparable despite the varied activity against various receptors. Bosentan is the most widely used pulmonary vasodilator which improves exercise tolerance and decelerates disease progression.

scholarly journals Medication adherence, hospitalization, and healthcare resource utilization and costs in patients with pulmonary arterial hypertension treated with endothelin receptor antagonists or phosphodiesterase type-5 inhibitors

2020 ◽  
Vol 10 (1) ◽  
pp. 204589401988008 ◽  
Author(s):  
Robert P. Frantz ◽  
Jerrold W. Hill ◽  
Cassandra A. Lickert ◽  
Rolin L. Wade ◽  
Michele R. Cole ◽  
...  
Keyword(s):  
Medication Adherence ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Endothelin Receptor Antagonists ◽  
Endothelin Receptor ◽  
Receptor Antagonists ◽  
Phosphodiesterase Type 5 Inhibitors ◽  
Proportion Of Days Covered ◽  
Pulmonary Arterial ◽  
Phosphodiesterase Type

Adherence to therapy for pulmonary arterial hypertension is essential to optimize patient outcomes, but data on real-world adherence to different pulmonary arterial hypertension drug classes are limited. This retrospective database analysis evaluated relationships between adherence, hospitalization, and healthcare costs in pulmonary arterial hypertension patients treated with endothelin receptor antagonists or phosphodiesterase type-5 inhibitors. From the IQVIA Adjudicated Health Plan Database, patients with pulmonary arterial hypertension were identified based on diagnostic codes and prescriptions for endothelin receptor antagonists (ambrisentan, bosentan, macitentan) or phosphodiesterase type-5 inhibitors (sildenafil, tadalafil) approved for pulmonary arterial hypertension. Patients were assigned to the class of their most recently initiated (index) pulmonary arterial hypertension therapy between 1 January 2009 and 30 June 2015. Medication adherence was measured by proportion of days covered; patients with proportion of days covered ≥80% were considered adherent. The proportion of adherent patients was higher for endothelin receptor antagonists (571/755; 75.6%) than for phosphodiesterase type-5 inhibitors (970/1578; 61.5%; P < 0.0001). In both groups, hospitalizations declined as proportion of days covered increased. Among adherent patients, those on endothelin receptor antagonists had a significantly lower hospitalization rate than those on phosphodiesterase type-5 inhibitors (23.1% versus 28.5%, P = 0. 0218), fewer hospitalizations (mean (standard deviation) 0.4 (0.8) versus 0.5 (0.9); P = 0.02), and mean hospitalization costs during the six-month post-index ($9510 versus $15,726, P = 0.0318). Increasing adherence reduced hospitalization risk more for endothelin receptor antagonists than for phosphodiesterase type-5 inhibitors (hazard ratio 0.176 versus 0.549, P = 0.001). Rates and numbers of rehospitalizations within 30 days post-discharge were similar between groups. Mean total costs were higher with endothelin receptor antagonists than phosphodiesterase type-5 inhibitors in all patients ($91,328 versus $72,401, P = 0.0003) and in adherent patients ($88,867 versus $56,300, P < 0.0001), driven by higher drug costs.

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