Selexipag in Pulmonary Arterial Hypertension: Most Updated Evidence From Recent Preclinical and Clinical Studies

Abstract

Pulmonary arterial hypertension (PAH) is a relatively rare disease that, due to its chronic nature, has always been difficult to treat effectively. Selexipag is an oral prostacyclin (PGI ) agonist that was approved by US Food and Drug Administration (US FDA) in December 2015 for the treatment of PAH. After its success in phase 1 and phase 2 clinical trials regarding the convenient oral twice-daily dosing and low side-effect profile, selexipag raised the hope of controlling the disease progression in PAH patients. In the recently completed multicentered phase 3 study (GRIPHON), selexipag has been shown to reduce death and hospitalization due to PAH significantly, an effect that was consistent across different ranges of maintenance dose. In the same study selexipag use was also associated with an increase in 6-minute walk distance (a measure of symptom severity) from baseline, but no significant improvement in all-cause mortality could be observed. The results of the ongoing phase 3 studies (TRITON and TRANSIT-1) are expected to throw some more light on the safety and efficacy of this novel molecule across various treatment scenarios. Hence, our article aims to summarize all the available information from preclinical and clinical studies published to date on the pharmacodynamics, pharmacokinetics, efficacy, safety (in general and in scenarios such as hepatic and renal function impairment), significant drug interactions (with warfarin and antiretroviral drugs), and clinical significance of oral selexipag in patients with PAH.

Selexipag-based triple combination therapy improves prognosis in Chinese pulmonary arterial hypertension patients

“…These results indicate that triple upfront combination therapy with drugs targeting the prostacyclin pathway may be necessary to achieve a more substantially improved prognosis in PAH patients ( 17 ). The GRIPHON trial demonstrated that the addition of selexipag in patients treated with ERA and PDE-5i further improved long-term outcomes ( 18 ). In the present study, 72.5% patients were already receiving a stable dose of ERAs and PDE5i, but we also noticed that sequential combination with selexipag improved the risk status.…”

Adaptações Estruturais De Coluna Vertebral, Cinturas E Gradil Costal Em Indivíduos Praticantes De Balé Clássico

“…Estudos demonstraram que a HAP possui associação com a redução da enzima prostaciclina sintase, que consequentemente, reduz os níveis de PGI2 endógeno. Logo, haverá uma diminuição nos níveis de fosfato de inositol (IP) e nos níveis de adenosina monofosfato (cAMP), que prejudica também a vasodilatação e a capacidade de resistência à proliferação pulmonar (Ghosh et al, 2016).…”

The <i>in Vitro</i> Characterisation of the Effect of Selexipag on Small Human Pulmonary Arteries

“…However, at the end of the study, 100 patients in the selexipag cohort died and 105 patients in the placebo cohort died. This showed that although selexipag reduced the risk of death during the treatment period, it did not improve the morbidity of the patients [28]. The recently completed TRITON (NCT02558231.…”