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
dc.contributor.author
dc.date.accessioned
2017-06-02T10:02:20Z
dc.date.available
2017-06-02T10:02:20Z
dc.date.issued
2017-02-13
dc.identifier.issn
1461-1457
dc.identifier.uri
dc.description.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
dc.format.mimetype
application/pdf
dc.language.iso
eng
dc.publisher
Oxford University Press (OUP)
dc.relation.isformatof
Reproducció digital del document publicat a: http://dx.doi.org/10.1093/ijnp/pyx012
dc.relation.ispartof
International Journal of Neuropsychopharmacology, 2017, vol 20, núm. 7, p. 519-528
dc.relation.ispartofseries
Articles publicats (D-CM)
dc.rights
Attribution-NonCommercial 3.0 Spain
dc.rights.uri
dc.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
dc.type
info:eu-repo/semantics/article
dc.rights.accessRights
info:eu-repo/semantics/openAccess
dc.embargo.terms
Cap
dc.type.version
info:eu-repo/semantics/publishedVersion
dc.identifier.doi
dc.identifier.idgrec
026726
dc.identifier.eissn
1469-5111