Dataset Information

Gabapentin and Pregabalin and Risk of Atrial Fibrillation in the Elderly: A Population-Based Cohort Study in an Electronic Prescription Database.

ABSTRACT:

Introduction

Gabapentin and pregabalin are widely prescribed to elderly people, but data on their pharmacokinetics, safety, and efficacy in this population are scarce. Neurological adverse effects are common. Atrial fibrillation (AF) associated with their use has been described in several case reports and case series, but the incidence is unknown.

Objective

The aim of this study was to assess the association between exposure to gabapentin or pregabalin and AF in the elderly.

Methods

Patients???65 years of age starting treatment with either gabapentin or pregabalin between January 1 and March 31, 2015, free of cardiovascular disease, and who did not receive the alternate study medications were studied. They were compared with patients who initiated treatment with an analgesic opiate or with alprazolam or diazepam. The two primary outcome variables were a first claim of an oral anticoagulant plus an antiarrhythmic drug (OAC?+?AA), or of an oral anticoagulant or an antiplatelet agent plus an antiarrhythmic drug (OAC/APA?+?AA), in the 3 months after treatment initiation.

Results

Compared with opiate analgesics, both gabapentin and pregabalin were associated with an increased risk of initiating OAC/APA?+?AA. The incidence was 6 of 668 (9.0 per 1000 patients) with gabapentin, versus 12 of 3889 (3.1 per 1000) with opiates, relative risk (RR) 2.91 (95% confidence interval [CI] 1.10-7.73), and for pregabalin it was 6 of 698 (8.6 per 1000) RR 2.79 (95% CI 1.05-7.40). The comparison with alprazolam/diazepam gave similar results. The risks did not vary by age, sex, or co-treatment with NSAIDs, and they increased with dose.

Conclusion

In elderly patients free of cardiovascular disease, an association between new exposure to gabapentin or pregabalin and initiating treatment for AF was found. These results should be confirmed in other studies.

SUBMITTER: Ortiz de Landaluce L

PROVIDER: S-EPMC6223696 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Publications

Gabapentin and Pregabalin and Risk of Atrial Fibrillation in the Elderly: A Population-Based Cohort Study in an Electronic Prescription Database.

Ortiz de Landaluce Leticia L Carbonell Pere P Asensio Carmen C Escoda Núria N López Pilar P Laporte Joan-Ramon JR

Drug safety 20181201 12

<h4>Introduction</h4>Gabapentin and pregabalin are widely prescribed to elderly people, but data on their pharmacokinetics, safety, and efficacy in this population are scarce. Neurological adverse effects are common. Atrial fibrillation (AF) associated with their use has been described in several case reports and case series, but the incidence is unknown.<h4>Objective</h4>The aim of this study was to assess the association between exposure to gabapentin or pregabalin and AF in the elderly.<h4>Me ...[more]

PMID: 29956217

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Project description:BackgroundPregabalin and gabapentin improve neuropathic pain symptoms but there are emerging concerns regarding their misuse. This is more pronounced among patients with substance use disorder, particularly involving opioids. Co-ingestion of gabapentinoids with opioids is increasingly identified in opioid related deaths, however, the molecular mechanism behind this is still unclear. We have sought to determine whether pregabalin or gabapentin directly modulates acute μ receptor signaling, or μ receptor activation by morphine.MethodsThe effects of pregabalin and gabapentin were assessed in HEK 293 cells stably transfected with the human μ receptor. Their effect on morphine induced hyperpolarization, cAMP production and ERK phosphorylation were studied using fluorescent-based membrane potential assay, bioluminescence based CAMYEL assay and ELISA assay, respectively. Pregabalin/gabapentin effects on morphine-induced hyperpolarization were also investigated in AtT20 cells.ResultsPregabalin or gabapentin (1 µM, 100 µM each) did not activate the µ receptor or affect K channel activation or ERK phosphorylation produced by morphine. Neither drug affected the desensitization of K channel activation produced by prolonged (30 min) application of morphine. Gabapentin (1 µM, 100 µM) and pregabalin (1 µM) did not affect inhibition of forskolin-stimulated cAMP production by morphine. However, pregabalin (100 µM) potentiated forskolin mediated cAMP production, although morphine still inhibited cAMP levels with a similar potency to control.DiscussionPregabalin or gabapentin did not activate or modulate µ receptor signaling in three different assays. Our data do not support the hypothesis that gabapentin or pregabalin augment opioid effects through direct or allosteric modulation of the µ receptor. Pregabalin at a high concentration increases cAMP production independent of morphine. The mechanism of enhanced opioid-related harms from co-ingestion of pregabalin or gabapentin with opioids needs further investigation.

Dataset Information

Gabapentin and Pregabalin and Risk of Atrial Fibrillation in the Elderly: A Population-Based Cohort Study in an Electronic Prescription Database.

Introduction

Objective

Methods

Results

Conclusion

Publications

Gabapentin and Pregabalin and Risk of Atrial Fibrillation in the Elderly: A Population-Based Cohort Study in an Electronic Prescription Database.

Similar Datasets

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