Pulmonary Hypertension Treatments Compared for Safety, Adverse Events

Pulmonary hypertension
Pulmonary hypertension
Individuals treated with riociguat for pulmonary hypertension may have a greater risk for gastrointestinal disorders compared with tadalafil and sildenafil.

Type 5 phosphodiesterase inhibitors tadalafil and sildenafil and the soluble guanylate cyclase stimulator riociguat may demonstrate different safety profiles and side effects that warrant a change in treatment for individuals with pulmonary hypertension, according to a study published by Chest.

Researchers performed a meta-analysis of the safety data from multiple randomized controlled studies, with a total of 7451 adverse drug events reported in 2979 individuals given sildenafil (n=529), tadalafil (n=745), riociguat (n=622), and placebo (n=1036) to treat pulmonary hypertension.

In addition, researchers performed a disproportionality analysis comparing the safety-profile of sildenafil (n=6642), tadalafil (n=3420), and riociguat (n=1539) with real-life data from VigiBase, the World Health Organization’s database of individual case safety reports to determine compare the safety and side effect profiles of these drugs. Adverse drug events in the safety reports regarding sildenafil, tadalafil, and riociguat were 17,919, 10,047, and 8569, respectively.

Study results of the meta-analysis of the 3 drugs demonstrated a significant difference only in gastrointestinal disorders, in that they were higher in those individuals treated with riociguat (P <.01). Individuals taking riociguat compared with sildenafil and tadalafil reported fewer visual disorders confirmed by the disproportionality analysis, yet a higher number of gastrointestinal, hemorrhagic, musculoskeletal, and vestibular (dizziness) disorders.

When compared sildenafil with tadalafil, fewer hearing (deafness)/vestibular and gastrointestinal disorders were found with tadalafil in both the meta-analysis and disproportionality analysis. Of note, the researchers found an increased risk for musculoskeletal disorders associated with tadalafil, while the disproportionality analysis found a stronger association with riociguat.

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Researchers concluded that overall riociguat was associated with more gastrointestinal, hemorrhagic, musculoskeletal, and vestibular disorders when compared with sildenafil and tadalafil. However, riociguat was associated with less hearing and visual disorders. Therefore, since the safety and side effect profiles of these drugs differ significantly, clinicians may choose to switch between them when treating individuals with pulmonary hypertension.


Khouri C, Lepelly M, Roustit M, et al. Comparative safety of drugs targeting the nitric oxide pathway in pulmonary hypertension [published online December 21, 2017]. Chest. doi:10.1016.j.chest.2017.12.008