Key result
Use of sulfonylurea antidiabetics, alone or with metformin, was associated with a reduced risk of out-of-hospital cardiac arrest compared to metformin monotherapy (OR 0.6; 95% CI 0.4-0.9).
Why the study?
Sulfonylurea antidiabetics can block myocardial KATP channels activated during AMI and modulate action potential duration, prompting investigation into their impact on OHCA risk and relationship to APD changes.
Do sulfonylurea drugs reduce the risk of out-of-hospital cardiac arrest in patients with diabetes compared to metformin?
Case-Control (n=916)
Do sulfonylurea drugs reduce the risk of out-of-hospital cardiac arrest in patients with diabetes compared to metformin?
Odds Ratio: 0.6 (95% CI 0.4–0.9)
Sulfonylurea drugs, particularly gliclazide, are associated with a lower risk of out-of-hospital cardiac arrest compared to metformin in patients with diabetes, though this effect does not appear to be mediated by changes in action potential duration.
Sulfonylurea use was associated with lower OHCA risk versus metformin; leaves open preferential prescribing pending prospective confirmation.
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.
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Eroglu et al. (2021) conducted a case-control in Diabetes and out-of-hospital cardiac arrest (n=916). Sulfonylurea antidiabetics (alone or with metformin) vs. Metformin monotherapy was evaluated on Out-of-hospital cardiac arrest (OHCA) risk (OR 0.6, 95% CI 0.4-0.9). Use of sulfonylurea antidiabetics, alone or with metformin, was associated with a reduced risk of out-of-hospital cardiac arrest compared to metformin monotherapy (OR 0.6; 95% CI 0.4-0.9).
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