BACKGROUND: Recent guidelines recommend riociguat, a soluble guanylate cyclase (sGC) stimulator, as well as the type 5 phosphodiesterase inhibitor (PDE5i) tadalafil or sildenafil as treatments for pulmonary arterial hypertension. We compared the safety profiles of sildenafil, tadalafil and riociguat in pulmonary hypertension.
METHODS: We combined two approaches: First, we performed a meta-analysis of safety data extracted from randomized controlled trials. Secondly, we conducted a disproportionality analysis of data from VigiBase, the WHO global database of individual case safety reports, to compare the safety profiles with real life data.
RESULTS: In the meta-analysis, a significant difference between the three drugs was only detected for gastro-intestinal disorders, in disfavour of riociguat (p<0.01 for interaction). In the disproportionality analysis, the use of riociguat was associated with fewer reports of visual disorders but increased reporting of gastrointestinal, haemorrhagic and musculoskeletal disorders than for sildenafil and tadalafil. Pharmacovigilance signals of hearing/vestibular disorders were heterogeneous: vestibular disorders (dizziness) were reported more frequently for riociguat whereas hearing disorders (deafness) were reported less frequently compared to PDE5i.
CONCLUSIONS: The safety profiles of PDE5i and sGC stimulators significantly differ in pulmonary hypertension. Accordingly, there is a safety rationale in switching between PDE5i and sGC stimulators due to their different side effects.
|組織名||Grenoble Alpes University Hospital, Pharmacovigilance Unit, F-38000 Grenoble,;France; Grenoble Alpes University Hospital, Clinical Pharmacology Department,;INSERM CIC1406, F-38000 Grenoble, France; Univ. Grenoble Alpes, UMR 1042-HP2,;INSERM, F-38000 Grenoble, France. Electronic address: CKhouri@chu-grenoble.fr.;France.;Grenoble Alpes University Hospital, Clinical Pharmacology Department, INSERM;CIC1406, F-38000 Grenoble, France; Univ. Grenoble Alpes, UMR 1042-HP2, INSERM,;F-38000 Grenoble, France.;Department of Medical and Clinical Pharmacology, Toulouse University Hospital,;Faculty of Medicine, 37 allees Jules Guesde, 31000 Toulouse, France.;Assistance Publique-Hopitaux de Paris, Service de Pneumologie, DHU Thorax;Innovation, Hopital Bicetre and Universite Paris-Sud, Laboratoire d'Excellence en;Recherche sur le Medicament et Innovation Therapeutique and INSERM Unite 999, Le;Kremlin-Bicetre, France.|