Sulfonylurea antidiabetics are associated with lower risk of out-of-hospital cardiac arrest: Real-world data from a population-based study
| Main Authors: | Eroglu, Talip E., Jia, Lixia, Blom, Marieke T., Verkerk, Arie O., Devalla, Harsha D., Boink, Gerard J.J., Souverein, Patrick C., de Boer, Anthonius, Tan, Hanno L. |
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| Format: | Article Journal |
| Terbitan: |
, 2021
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| Online Access: |
https://zenodo.org/record/5142375 |
Daftar Isi:
- 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.
- This work was supported by the European Union's Horizon 2020 research and innovation programme under the acronym ESCAPE-NET, registered under grant agreement No. 733381 (T.E.E., M.T.B., H.L.T.), and the COST Action PARQ (grant agreement No. CA19137) supported by COST (European Cooperation in Science and Technology), and the Netherlands CardioVascular Research Initiative (Dutch Heart Foundation, Dutch Federation of University Medical Centers, Netherlands Organization for Health Research and Development, and Royal Netherlands Academy of Sciences) grants CVON-2017-15 RESCUED (H.L.T.) and CVON-2018-30 Predict-2 (M.T.B., H.L.T.). The ARREST registry is supported by an unconditional grant from Physio-Control Inc., part of Stryker, Redmond, WA, USA. The funders were not involved in designing the study, collecting and analysing the data, preparing the manuscript, or the decision to publish.