The medication Adempas (riociguat) effectively improves several hemodynamic parameters in patients with pulmonary arterial hypertension (PAH), according to the Phase 3 PATENT-1 clinical trial.
Results showed that the drug improved these parameters — which included pulmonary vascular resistance (PVR), right atrial pressure (RAP) and cardiac index — not only in PAH patients being treated for the first time, but also in those undergoing other therapeutic protocols.
These observations resulted from the phase 3 PATENT-1 clinical trial.
The study, “Comparison of hemodynamic parameters in treatment-naïve and pre-treated patients with pulmonary arterial hypertension in the randomized phase III PATENT-1 study,” appeared in The Journal of Heart and Lung Transplantation.
The PATENT-1 trial (NCT00810693) assessed the efficacy and safety of Adempas in patients with symptomatic PAH. Conducted at 124 centers in 30 countries, it enrolled 221 PAH patients who were never treated and 222 PAH patients who were previously undergoing treatment with other drugs.
Of the pre-treated patients, 194 were receiving treatment with the endothelin receptor antagonists (ERAs) Tracleer and Letairis, and 31 were receiving one of three non-intravenous prostanoids: Ventavis, Beraprost and treprostinil (Remodulin, Orenitram and Tyvaso).
PAH patients were divided into two groups, the Adempas-treated group and a placebo control group. All participants underwent a 12-week treatment protocol with oral administration of Adempas between 0.5 or 2.5 mg, three times daily.
Results showed that at week 12, all treated patients showed improvement of a range of hemodynamic parameters compared with placebo group. PVR values fell by 28 percent and SVR dropped as well, while the cardiac response (measured by cardiac index calculation) rose 21 percent. Other parameters such as mean pulmonary artery pressure (mPAP), cardiac output (CO), mixed venous oxygen saturation (SvO2) and mean arterial pressure (MAP) also recorded “significant positive changes,” according to the study.
These improvements were consistent across the first-time treated and pre-treated patient subgroups, while ERAs and non-intravenous prostanoids pre-treated patients showed no significant differences.
Adempas treatment also improved results of the six-minute walk distance test (which assesses exercise capacity) of pre-treated and first-time treated PAH patients.
The study revealed some adverse side effects of Adempas, though they were uncorrelated to any of the subgroups of PAH patients analyzed, and not different from the placebo control group.
“The mechanisms underlying the hemodynamic improvements observed with riociguat [Adempas] have yet to be elucidated,” the authors wrote. “Whether potentially disease-modifying effects of riociguat, such as the anti-fibrotic, anti-proliferative and anti-inflammatory effects observed in pre-clinical studies, play a role is unknown and requires further characterization.”
Authors concluded that Adempas could be a possible treatment option for patients with PAH, and that it could be used either as a monotherapy or in combination with ERAs and non-intravenous prostanoids.