Gabapentinoid-induced peripheral edema and acute heart failure: A translational study combining pharmacovigilance data and in vitro animal experiments

• DOI: 10.1016/j.biopha.2022.112807
• Publication Date: 2022-03-15T11:22:46Z
• Authors: Bérenger Largeau; Romain Bordy; Côme Pasqualin; Pierre Bredeloux; Jean-Luc Cracowski; Céline Lengellé; Valérie Gras-Champel; Marine Auffret; Véronique Maupoil; Annie-Pierre Jonv...
• Keywords: Peripheral edema; Pregabalin

Gabapentinoids are ligands of the α2-δ subunit voltage-gated calcium channels (Cav) that have been associated with a risk peripheral edema and acute heart failure in connection potentially dual mechanism, vascular cardiac.All cases or involving gabapentin pregabalin reported to French Pharmacovigilance Centers between January 1, 1994 April 30, 2020 were included describe their onset patterns (e.g., time onset). Based on these data, we investigated impact gabapentinoids myogenic tone rat third-order mesenteric arteries electrophysiological properties ventricular cardiomyocytes.A total 58 reports (gabapentin n = 5, 53). The female-to-male ratio was 4:1 median age 77 years (IQR 57-85, range 32-95). 23 days 10-54) 17 3-30) for non-cardiogenic failure, respectively. Cardiogenic occurred frequently after dose escalation (27/45, 60%), course rapidly favorable discontinuation gabapentinoid (median 7 days, IQR 5-13). On arteries, significantly decreased same extent as verapamil nifedipine. Acute application had no significant effect Cav1.2 currents cardiomyocytes.Gabapentinoids can cause concentration-dependent early onset. primary mechanism is vasodilatory secondary altered tone, independent blockade under experimental conditions tested.