Vericiguat Enhances Olfactory Function in Post-Infectious Anosmia: A Randomized Pilot Double-Blind Placebo-Controlled Trial

BackgroundOlfactory dysfunction affects approximately 29% of the population and has a profound impact on quality of life. It frequently follows upper respiratory tract infections and lacks effective pharmacological treatments. Vericiguat, a soluble guanylate cyclase stimulator that increases intracellular cyclic guanosine monophosphate, is approved for heart failure and has potential neuro-modulatory effects relevant to olfactory processing.ObjectiveThis pilot study investigates the efficacy of oral vericiguat in improving olfactory function in patients with persistent anosmia following upper respiratory tract infections.MethodsIn a double-blind, randomized controlled trial, 88 participants with post-infectious anosmia were assigned to receive either placebo (n = 44) or vericiguat (4 mg, twice daily; n = 44) for 12 months. Olfactory function was assessed monthly using the Sniffin' Sticks test, measuring Threshold (T), Discrimination (D), and Identification (I) scores. Data were analyzed using repeated-measures ANOVA and post-hoc Bonferroni corrections.ResultsAt baseline, all olfactory scores were similar between groups. In the vericiguat group, T scores increased from 3.84 ± 0.19 to 4.65 ± 0.20 (P = 0.003), D scores from 8.25 ± 0.65 to 9.20 ± 0.86 (P = 0.008), and I scores from 7.34 ± 0.72 to 8.62 ± 0.79 (P = 0.008). No significant changes were observed in the placebo group. Between-group differences became statistically significant for D at month 4 (P < 0.05), T at month 6 (P < 0.05), and I at month 7 (P < 0.05). However, the mean total TDI improvement in the vericiguat group (+ 3.19) did not reach the clinical threshold of 5.5 points.ConclusionVericiguat significantly improved olfactory threshold, discrimination, and identification scores compared to placebo. These findings highlight its potential as a pharmacological option for olfactory dysfunction, although the clinical magnitude of benefit remains below the established threshold. Further studies should explore mechanisms and broader clinical applications.Trial registrationDFM-IRB00012367-23-07-008.