Efficacy and safety of novel-targeted drugs in the treatment of pulmonary arterial hypertension: a Bayesian network meta-analysis

Abstract

Background: Pulmonary arterial hypertension (PAH) is a severe and fatal clinical syndrome characterized by high blood pressure and vascular remodeling in the pulmonary arterioles, which is also a rapidly progressing disease of the lung vasculature with a poor prognosis. Although PAH medication made great advances in recent years, the efficacy and safety of the medication are unsatisfactory. Therefore, we aimed to update and expand previous studies to explore the efficacy and safety of PAH-targeted medications. Methods: Relevant articles were searched and selected from published or publicly available data in PubMed, Cochrane Library, CNKI, PsycInfo, and MEDLINE (from inception until October 1 st , 2020). To assess the efficacy and safety of PAH therapies, five efficacy outcomes [6-minute walking distance (6MWD), mean pulmonary arterial pressure (mPAP), WHO functional class (WHO FC) improvement, clinical worsening, death] and two safety outcomes [adverse events (AEs), serious adverse events (SAEs)] were selected. And 6MWD was regarded as the primary efficacy outcome. Results: 50 trials included with 10 996participants were selected. In terms of efficacy, all targeted drugs were more effective than placebo. For 6MWD, Bosentan + Sildenafil, Sildenafil, Bosentan + Iloprost were better than others. Bosentan + Iloprost and Bosentan + Sildenafil were better for mPAP. Bosentan + Iloprost and Ambrisentan + Tadalafil were more effective in improving WHO FC. Bosentan + Tadalafil and Bosentan + Iloprost had the Ambrisentan probability to reduce the incidence of clinical worsening. It is demonstrated that Ambrisentan had clear benefits in reducing all-cause mortality. In terms of safety, no therapies had been shown to reduce the incidence of SAEs significantly, and Ambrisentan + Tadalafil significantly increased the incidence of AEs. Conclusions: Phosphodiesterase 5 inhibitor (PDE5i) + Endothelin Receptor Antagonists (ERA) seems to be better therapy for PAH. Prostacyclin analogs (ProsA) + ERA appear promising, though additional data is warranted. Registration PROSPERO CRD42020218818.

Sildenafil for congenital heart diseases induced pulmonary hypertension, a meta-analysis of randomized controlled trials.

“…However, it showed no signi cant improvement over sildena l in any of the hemodynamics parameters. Moreover, in a recent network-meta-analysis [34] conducted on PAH in adults, tadala l was associated with low change in 6 minute walking distance, besides associated with high clinical worsening compared to other PDE-inhibitors. Bosentan with Iloprost and Bosentan with Sildena l were the better combinations associated with lowest mPAP.…”

Is tadalafil associated with decreased risk of major adverse cardiac events or venous thromboembolism in men with lower urinary tract symptoms?

“…Of the popular PDE5Is, some patients prefer tadalafil over sildenafil for treatment of erectile dysfunction, possibly because of its longer duration of effect as it has the longest half-life (17.5 h.) of the commonly used PDE5Is tadalafil, sildenafil, and vardenafil [ 26 , 27 ]. PDE5I use is not limited to LUTS and sexual dysfunction; in combination with other drugs, they are used successfully to treat pulmonary artery hypertension [ 28 ]. Tadalafil is now more accessible than ever; it became a generic drug when its patent expired in November 2017, leading to a 49% decrease in cost per unit [ 29 ].…”

Medications for the treatment of pulmonary arterial hypertension: a systematic review and network meta-analysis

“…Other NMAs of PAH treatments have been reported [ 77 , 78 ]. A 2017 NMA presented data from 31 RCTs and found similar benefits of PAH treatments with regards to reduced clinical worsening [ 78 ].…”