A Systematic Literature Review Exploring the Efficacy and Safety of Tadalafil and Sildenafil in Pulmonary Arterial Hypertension

Pulmonary Arterial Hypertension (PAH) is a rare, chronic and progressive disease affecting the heart and lungs. Endothelin receptor antagonist (ERA) + phosphodiesterase type 5 inhibitor (PDE5i) treatment is recommended for all PAH patients. The two approved PDE5is are tadalafil and sildenafil. To determine the efficacy and safety outcomes for tadalafil and sildenafil as monotherapies or in combination with ERAs for treating PAH, from randomized controlled trials (RCTs) and real-world evidence studies (RWEs) identified by a systematic literature review (SLR). MEDLINE, Embase and Cochrane Libraries were searched in May 2024. Relevant outcomes included 6-min walk distance (6MWD), pulmonary vascular resistance (PVR) and safety. This report includes studies where patients were treated with either sildenafil or tadalafil. Fifteen RCTs and three RWEs investigated tadalafil (tadalafil 40 mg or 20 mg once daily) or sildenafil (20 mg three times a day). Mean 6MWD change from baseline (CFB) in patients receiving tadalafil or sildenafil monotherapy were comparable, however, in combination with an ERA, tadalafil may be more effective. Generally, there was more data for tadalafil + ERAs, showing marked improvement in mean PVR CFB, compared with patients receiving sildenafil. Conclusions on safety were limited. Risk of bias in RCTs was generally low but moderate in RWEs. Two studies reported patients who switched from sildenafil to tadalafil treatment, treatment transition was feasible. Although comparable when used as monotherapy, this qualitative analysis suggests that tadalafil + ERA combination therapy may have more favorable 6MWD improvements than sildenafil + ERA combination therapy.