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Cholinesterase inhibitors-associated torsade de pointes/QT prolongation: a real-world pharmacovigilance study

Ni Zhang1, Lanlan Gan1, Guiyuan Xiang1

  • 1Department of Pharmacy, Daping Hospital, Army Medical University, Chongqing, China.

Frontiers in Pharmacology
|January 26, 2024
PubMed

Insights

Cholinesterase inhibitors (ChEIs) used for Alzheimer's disease show a strong link to QT prolongation and TdP. This risk is higher in elderly women and during the initial month of treatment, especially with certain drug combinations.

Area of Science:

  • Pharmacovigilance
  • Cardiology
  • Geriatrics

Background:

  • Cholinesterase inhibitors (ChEIs) are primary treatments for Alzheimer's disease (AD).
  • Understanding the cardiac risks, specifically Torsade de Pointes (TdP) and QT prolongation, associated with ChEIs is crucial for patient safety.
  • This study investigates the relationship between various ChEIs and the occurrence of TdP/QT prolongation.

Purpose of the Study:

  • To evaluate the correlation between different Cholinesterase inhibitors (ChEIs) and the risk of Torsade de Pointes (TdP)/QT prolongation.
  • To identify specific ChEIs with a higher association with these cardiac events.
  • To analyze risk factors and co-medications associated with ChEI-induced TdP/QT prolongation.

Main Methods:

  • Utilized the FDA Adverse Event Reporting System (FAERS) database for case retrieval.
  • Employed Standard MedDRA Queries (SMQ) to identify relevant cases of TdP/QT prolongation linked to ChEIs from Q1 2004 to Q3 2022.
  • Applied disproportionality and sensitivity analyses to detect and confirm safety signals.

Main Results:

  • Identified 557 cases of TdP/QT prolongation associated with three different ChEIs.
  • Disproportionality analysis revealed significant safety signals for TdP/QT prolongation with ChEIs, with Donepezil showing the strongest signal.
  • Sensitivity analysis confirmed a robust and stable correlation. Events typically occurred within one month of initiating ChEI therapy, predominantly in elderly females. Citalopram was frequently co-prescribed with Donepezil and Galantamine, while Atorvastatin was common with Rivastigmine.

Conclusions:

  • Strong and stable safety signals for TdP/QT prolongation exist for Cholinesterase inhibitors (ChEIs).
  • Vigilance is required regarding the cardiac risks of all ChEIs, particularly in elderly women.
  • Consideration of co-medications known to prolong the QT interval is essential, especially during the initial treatment phase.

Keywords:
FAERScholinesterase inhibitorsdrug safetypharmacovigilance studytorsade de pointes/QT prolongation

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