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Sulfonylurea antidiabetics are associated with lower risk of out-of-hospital cardiac arrest: Real-world data from a population-based study

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DOI

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  1. Opioid use is associated with increased out-of-hospital cardiac arrest risk among 40,000-cases across two countries

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Out-of-hospital cardiac arrest and differential risk of cardiac and non-cardiac QT-prolonging drugs in 37,000 cases

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Temporal variation in out-of-hospital cardiac arrest occurrence in individuals with or without diabetes

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Talip E Eroglu
  • Lixia Jia
  • Marieke T Blom
  • Arie O Verkerk
  • Harsha D Devalla
  • Gerard J J Boink
  • Patrick C Souverein
  • Anthonius de Boer
  • Hanno L Tan
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AIMS: Out-of-hospital cardiac arrest (OHCA) mostly results from ventricular tachycardia/ventricular fibrillation (VT/VF), often triggered by acute myocardial infarction (AMI). Sulfonylurea (SU) antidiabetics can block myocardial ATP-regulated K+ channels (KATP channels), activated during AMI, thereby modulating action potential duration (APD). We studied whether SU drugs impact on OHCA risk, and whether these effects are related to APD changes.

METHODS: We conducted a population-based case-control study in 219 VT/VF-documented OHCA cases with diabetes and 697 non-OHCA controls with diabetes. We studied the association of SU drugs (alone or in combination with metformin) with OHCA risk compared to metformin monotherapy, and of individual SU drugs compared to glimepiride, using multivariable logistic regression analysis. We studied the effects of these drugs on APD during simulated ischaemia using patch-clamp studies in human induced pluripotent stem cell-derived cardiomyocytes.

RESULTS: Compared to metformin, use of SU drugs alone or in combination with metformin was associated with reduced OHCA risk (ORSUdrugs-alone 0.6 [95% CI 0.4-0.9], ORSUdrugs + metformin 0.6 [95% CI 0.4-0.9]). We found no differences in OHCA risk between SU drug users who suffered OHCA inside or outside the context of AMI. Reduction of OHCA risk compared to glimepiride was found with gliclazide (ORadj 0.5 [95% CI 0.3-0.9]), but not glibenclamide (ORadj 1.3 [95% CI 0.6-2.7]); for tolbutamide, the association with reduced OHCA risk just failed to reach statistical significance (ORadj 0.6 [95% CI 0.3-1.002]). Glibenclamide attenuated simulated ischaemia-induced APD shortening, while the other SU drugs had no effect.

CONCLUSIONS: SU drugs were associated with reduced OHCA risk compared to metformin monotherapy, with gliclazide having a lower risk than glimepiride. The differential effects of SU drugs are not explained by differential effects on APD.

Original languageEnglish
JournalBritish Journal of Clinical Pharmacology
Volume87
Issue number9
Pages (from-to)3588-3598
Number of pages11
ISSN0306-5251
DOIs
Publication statusPublished - Sep 2021

Bibliographical note

© 2021 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

    Research areas

  • Case-Control Studies, Humans, Hypoglycemic Agents/therapeutic use, Induced Pluripotent Stem Cells, Out-of-Hospital Cardiac Arrest/drug therapy, Ventricular Fibrillation/epidemiology

ID: 72414571