Discontinuation, Efficacy, and Safety of Cholinesterase Inhibitors for Alzheimer%26apos;s Disease: a Meta-Analysis and Meta-Regression of 43 Randomized Clinical Trials Enrolling 16 106 Patients

作者：Blanco Silvente Lidia; Castells Xavier; Saez Marc; Antonia Barcelo Maria; Garre Olmo Josep; Vilalta Franch Joan; Capella Dolors

来源：International Journal of Neuropsychopharmacology, 2017, 20(7): 519-528.

DOI：10.1093/ijnp/pyx012

• cholinesterase inhibitor
• Alzheimer's disease
• discontinuation
• efficacy
• Bayesian meta-analysis

Background: 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 16 106 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 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 patientrelated factors modify the effect of cholinesterase inhibitors in patients with Alzheimer's disease.

• 出版日期2017-7