{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T11:39:26Z","timestamp":1770982766210,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T00:00:00Z","timestamp":1619308800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Out\u2010of\u2010hospital 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\u2010regulated K<jats:sup>+<\/jats:sup> channels (K<jats:sub>ATP<\/jats:sub> 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a population\u2010based case\u2013control study in 219 VT\/VF\u2010documented OHCA cases with diabetes and 697 non\u2010OHCA 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\u2010clamp studies in human induced pluripotent stem cell\u2010derived cardiomyocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to metformin, use of SU drugs alone or in combination with metformin was associated with reduced OHCA risk (OR<jats:sub>SUdrugs\u2010alone<\/jats:sub> 0.6 [95% CI 0.4\u20130.9], OR<jats:sub>SUdrugs\u00a0+\u00a0metformin<\/jats:sub> 0.6 [95% CI 0.4\u20130.9]). 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 (OR<jats:sub>adj<\/jats:sub> 0.5 [95% CI 0.3\u20130.9]), but not glibenclamide (OR<jats:sub>adj<\/jats:sub> 1.3 [95% CI 0.6\u20132.7]); for tolbutamide, the association with reduced OHCA risk just failed to reach statistical significance (OR<jats:sub>adj<\/jats:sub> 0.6 [95% CI 0.3\u20131.002]). Glibenclamide attenuated simulated ischaemia\u2010induced APD shortening, while the other SU drugs had no effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14774","type":"journal-article","created":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T10:35:21Z","timestamp":1619346921000},"page":"3588-3598","source":"Crossref","is-referenced-by-count":12,"title":["Sulfonylurea antidiabetics are associated with lower risk of out\u2010of\u2010hospital cardiac arrest: Real\u2010world data from a population\u2010based study"],"prefix":"10.1111","volume":"87","author":[{"given":"Talip E.","family":"Eroglu","sequence":"first","affiliation":[{"name":"Department of Cardiology, Heart Center, Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"},{"name":"Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences Utrecht University  Utrecht The Netherlands"},{"name":"Department of Cardiology Copenhagen University Hospital Herlev and Gentofte  Hellerup 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of Cardiology, Heart Center, Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"},{"name":"Department of Medical Biology, Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerard J.J.","family":"Boink","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Center, Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"},{"name":"Department of Medical Biology, Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7452-0477","authenticated-orcid":false,"given":"Patrick C.","family":"Souverein","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences Utrecht University  Utrecht The 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