Article type
Year
Abstract
Background: Cholinesterase inhibitors (CI) are commonly prescribed to treat the symptoms of Alzheimer’s disease (AD). An aging population will increase the number of CI users, who are more prone to the adverse effects (AE) of these drugs. Many of the AE are potentially severe, such as syncope and its consequences. Until recently their AE profile has received little attention.
Objectives: 1) To compare the efficiency of methods of identifying and confirming the specific association of bradycardia and related serious consequences with CI (BRSCI) in a systematic review (SR) of the biomedical literature with that of the United States Food and Drug Administration (FDA) spontaneous Adverse Event Reporting System (AERS) database; 2) To determine which method could have detected the AE earlier; 3) To determine whether differences exist in these AE between the various CI.
Methods: We performed a SR and descriptive analysis of primary, secondary (reviews) and tertiary literature (critical summaries) of the composite event of: bradycardia, bradyarrythmia, pacemaker insertion, complete atrio-ventricular block and hip fracture, associated with CI. We performed an analysis of the AERS database searching for the composite event (AERSDACE), using the Bayesian 'Multi Gamma Poisson Shrinker’ method.
Results: None of the clinical trials detected a single BRSCI adverse event. 13 patients with BRSCI were identified through case reports. Three large cohort studies yielded 831 individuals with BRSCI. A total of 246 patients were identified that possessed one or more of the defined composite AE through AERSDACE. A statistically strong signal of disproportionate reporting was observed by the Empirical Bayesian Geometric Mean, 7.07 (95%CI: 6.23-8.03), detected at one year after approval.
Conclusions: Publication of case reports of CI’s AE are a less efficient form of detection and epidemiological studies take many years to test a hypothesis. Analysis of large spontaneous adverse event databases is the most efficient primary source to identify non-common AE.
Objectives: 1) To compare the efficiency of methods of identifying and confirming the specific association of bradycardia and related serious consequences with CI (BRSCI) in a systematic review (SR) of the biomedical literature with that of the United States Food and Drug Administration (FDA) spontaneous Adverse Event Reporting System (AERS) database; 2) To determine which method could have detected the AE earlier; 3) To determine whether differences exist in these AE between the various CI.
Methods: We performed a SR and descriptive analysis of primary, secondary (reviews) and tertiary literature (critical summaries) of the composite event of: bradycardia, bradyarrythmia, pacemaker insertion, complete atrio-ventricular block and hip fracture, associated with CI. We performed an analysis of the AERS database searching for the composite event (AERSDACE), using the Bayesian 'Multi Gamma Poisson Shrinker’ method.
Results: None of the clinical trials detected a single BRSCI adverse event. 13 patients with BRSCI were identified through case reports. Three large cohort studies yielded 831 individuals with BRSCI. A total of 246 patients were identified that possessed one or more of the defined composite AE through AERSDACE. A statistically strong signal of disproportionate reporting was observed by the Empirical Bayesian Geometric Mean, 7.07 (95%CI: 6.23-8.03), detected at one year after approval.
Conclusions: Publication of case reports of CI’s AE are a less efficient form of detection and epidemiological studies take many years to test a hypothesis. Analysis of large spontaneous adverse event databases is the most efficient primary source to identify non-common AE.