Differential effects on out-of-hospital cardiac arrest of dihydropyridines: real-world data from population-based cohorts across two European countries
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Publication date
2020-11
Authors
Eroglu, Talip E.
Mohr, Grimur H.
Blom, Marieke T.
Verkerk, Arie O.
Souverein, Patrick C.
Torp-Pedersen, Christian
Folke, Fredrik
Wissenberg, Mads
van den Brink, Lettine
Davis, Richard P.
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Article
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Abstract
AIMS: Various drugs increase the risk of out-of-hospital cardiac arrest (OHCA) in the general population by impacting cardiac ion channels, thereby causing ventricular tachycardia/fibrillation (VT/VF). Dihydropyridines block L-type calcium channels, but their association with OHCA risk is unknown. We aimed to study whether nifedipine and/or amlodipine, often-used dihydropyridines, are associated with increased OHCA risk, and how these drugs impact on cardiac electrophysiology. METHODS AND RESULTS: We conducted a case-control study with VT/VF-documented OHCA cases with presumed cardiac cause from ongoing population-based OHCA registries in the Netherlands and Denmark, and age/sex/index date-matched non-OHCA controls (Netherlands: PHARMO Database Network, Denmark: Danish Civil Registration System). We included 2503 OHCA cases, 10 543 non-OHCA controls in Netherlands, and 8101 OHCA cases, 40 505 non-OHCA controls in Denmark. To examine drug effects on cardiac electrophysiology, we performed single-cell patch-clamp studies in human-induced pluripotent stem cell-derived cardiomyocytes. Use of high-dose nifedipine (≥60 mg/day), but not low-dose nifedipine (
Keywords
Amlodipine, Epidemiology, Nifedipine, Sudden cardiac arrest, action potential, adult, article, calcium current, cardiac muscle cell, case control study, controlled study, Denmark, drug effect, drug megadose, female, heart electrophysiology, heart ventricle tachycardia, human, human cell, induced pluripotent stem cell, ischemic heart disease, low drug dose, major clinical study, male, Netherlands, out of hospital cardiac arrest, patch clamp technique, sudden cardiac death, titrimetry, amlodipine, calcium channel L type, endogenous compound, nifedipine, nitric acid derivative, SDG 3 - Good Health and Well-being
Citation
Eroglu, T E, Mohr, G H, Blom, M T, Verkerk, A O, Souverein, P C, Torp-Pedersen, C, Folke, F, Wissenberg, M, van den Brink, L, Davis, R P, de Boer, A, Gislason, G H & Tan, H L 2020, 'Differential effects on out-of-hospital cardiac arrest of dihydropyridines : real-world data from population-based cohorts across two European countries', European heart journal. Cardiovascular pharmacotherapy, vol. 6, pp. 347-355. https://doi.org/10.1093/ehjcvp/pvz038