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Discontinuation, Efficacy, and Safety of Cholinesterase Inhibitors for Alzheimer’s Disease: a Meta-Analysis and Meta-Regression of 43 Randomized Clinical Trials Enrolling 16.106 Patients

We investigated the effect of cholinesterase inhibitors on all-cause discontinuation, efficacy and safety, and the effects of study design-, intervention-, and patient-related covariates on the risk-benefit of cholinesterase inhibitors for Alzheimer’s disease. Methods: A systematic review and meta-analysis of randomized placebo-controlled clinical trials comparing cholinesterase inhibitors and placebo was performed. The effect of covariates on study outcomes was analysed by means of meta-regression using a Bayesian framework. Results: Forty-three randomized placebo-controlled clinical trials involving 16106 patients were included. All-cause discontinuation was higher with cholinesterase inhibitors (OR = 1.66), as was discontinuation due to adverse events (OR=1.75). Cholinesterase inhibitors improved cognitive function (standardized mean difference = 0.38), global symptomatology (standardized mean difference=0.28) and functional capacity (standardized mean difference=0.16) but not neuropsychiatric symptoms. Rivastigmine was associated with a poorer outcome on all-cause discontinuation (Diff OR = 1.66) and donepezil with a higher efficacy on global change (Diff standardized mean difference = 0.41). The proportion of patients with serious adverse events decreased with age (Diff OR = -0.09). Mortality was lower with cholinesterase inhibitors than with placebo (OR = 0.65). Conclusion: While cholinesterase inhibitors show a poor risk-benefit relationship as indicated by mild symptom improvement and a higher than placebo all-cause discontinuation, a reduction of mortality was suggested. Intervention- and patient-related factors modify the effect of cholinesterase inhibitors in patients with Alzheimer’s disease

International Journal of Neuropsychopharmacology, 2017, vol 20, núm. 7, p. 519-528

Oxford University Press (OUP)

Author: Blanco Silvente, Lídia
Castells Cervelló, Xavier
Sáez Zafra, Marc
Barceló Rado, María Antonia
Garre Olmo, Josep
Vilalta Franch, Joan
Capellà Hereu, Dolors
Date: 2017 February 13
Abstract: We investigated the effect of cholinesterase inhibitors on all-cause discontinuation, efficacy and safety, and the effects of study design-, intervention-, and patient-related covariates on the risk-benefit of cholinesterase inhibitors for Alzheimer’s disease. Methods: A systematic review and meta-analysis of randomized placebo-controlled clinical trials comparing cholinesterase inhibitors and placebo was performed. The effect of covariates on study outcomes was analysed by means of meta-regression using a Bayesian framework. Results: Forty-three randomized placebo-controlled clinical trials involving 16106 patients were included. All-cause discontinuation was higher with cholinesterase inhibitors (OR = 1.66), as was discontinuation due to adverse events (OR=1.75). Cholinesterase inhibitors improved cognitive function (standardized mean difference = 0.38), global symptomatology (standardized mean difference=0.28) and functional capacity (standardized mean difference=0.16) but not neuropsychiatric symptoms. Rivastigmine was associated with a poorer outcome on all-cause discontinuation (Diff OR = 1.66) and donepezil with a higher efficacy on global change (Diff standardized mean difference = 0.41). The proportion of patients with serious adverse events decreased with age (Diff OR = -0.09). Mortality was lower with cholinesterase inhibitors than with placebo (OR = 0.65). Conclusion: While cholinesterase inhibitors show a poor risk-benefit relationship as indicated by mild symptom improvement and a higher than placebo all-cause discontinuation, a reduction of mortality was suggested. Intervention- and patient-related factors modify the effect of cholinesterase inhibitors in patients with Alzheimer’s disease
Format: application/pdf
Citation: 026726
ISSN: 1461-1457 (versió paper)
1469-5111 (versió electrònica)
Document access: http://hdl.handle.net/10256/14145
Language: eng
Publisher: Oxford University Press (OUP)
Collection: Reproducció digital del document publicat a: http://dx.doi.org/10.1093/ijnp/pyx012
Articles publicats (D-CM)
Is part of: International Journal of Neuropsychopharmacology, 2017, vol 20, núm. 7, p. 519-528
Rights: Attribution-NonCommercial 3.0 Spain
Rights URI: http://creativecommons.org/licenses/by-nc/3.0/es/
Subject: Alzheimer, Malaltia d’
Alzheimer’s disease
Assaigs clínics
Clinical trials
Title: Discontinuation, Efficacy, and Safety of Cholinesterase Inhibitors for Alzheimer’s Disease: a Meta-Analysis and Meta-Regression of 43 Randomized Clinical Trials Enrolling 16.106 Patients
Type: info:eu-repo/semantics/article
Repository: DUGiDocs

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