Open AccessDifferential effects on out-of-hospital cardiac arrest of dihydropyridines: real-world data from population-based cohorts across two European countries
Author(s) -
Talip E Eroglu,
Grímur Høgnason Mohr,
Marieke T. Blom,
Arie O. Verkerk,
Patrick C. Souverein,
Christian TorpPedersen,
Fredrik Folke,
Mads Wissenberg,
Lettine van den Brink,
Richard Davis,
Anthonius de Boer,
Gunnar Gislason,
Hanno L. Tan
Publication year - 2019
Publication title -
european heart journal. cardiovascular pharmacotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.895
H-Index - 26
eISSN - 2055-6845
pISSN - 2055-6837
DOI - 10.1093/ehjcvp/pvz038
Subject(s) - medicine , nifedipine , amlodipine , ventricular tachycardia , cardiology , ventricular fibrillation , population , odds ratio , anesthesia , blood pressure , environmental health , calcium
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 (<60 mg/day) or amlodipine (any-dose), was associated with higher OHCA risk than non-use of dihydropyridines [Netherlands: adjusted odds ratios (ORadj) 1.45 (95% confidence interval 1.02–2.07), Denmark: 1.96 (1.18–3.25)] or use of amlodipine [Netherlands: 2.31 (1.54–3.47), Denmark: 2.20 (1.32–3.67)]. Out-of-hospital cardiac arrest risk of (high-dose) nifedipine use was not further increased in patients using nitrates, or with a history of ischaemic heart disease. Nifedipine and amlodipine blocked L-type calcium channels at similar concentrations, but, at clinically used concentrations, nifedipine caused more L-type calcium current block, resulting in more action potential shortening. Conclusion High-dose nifedipine, but not low-dose nifedipine or any-dose amlodipine, is associated with increased OHCA risk in the general population. Careful titration of nifedipine dose should be considered.