TY - JOUR
T1 - Multiple categories of non-cardiac QT-prolonging drugs are associated with increased risk of out-of-hospital cardiac arrest
T2 - real-world data from a population-based study
AU - Eroglu, Talip E
AU - Blom, Marieke T
AU - Souverein, Patrick C
AU - de Boer, Anthonius
AU - Tan, Hanno L
N1 - © The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.
PY - 2022/4/5
Y1 - 2022/4/5
N2 - AIM: Drugs causing QT-prolongation as off-target effect [non-cardiac QT-prolonging drugs (QT-drugs)] increase the risk of out-of-hospital cardiac arrest (OHCA). Such drugs are categorized in multiple clinically widely used CredibleMeds.org lists. Category 1 ('known risk of Torsade de Pointes') and category 2 ('possible risk of Torsade de Pointes') are of particular clinical relevance. However, a category-stratified analysis of OHCA-risk is presently unavailable.METHODS AND RESULTS: We conducted a case-control study with OHCA-cases from presumed cardiac causes included from the ARREST registry in the Netherlands (2009-2018) that was specifically designed to study OHCA, and age/sex/OHCA-date matched non-OHCA-controls. Adjusted odds ratios for OHCA (ORadj) of QT-drugs from categories 1 or 2 were calculated, using conditional logistic regression. Stratified analysis was performed according to sex, age, and presence of cardiovascular drugs (proxy for cardiovascular disease). We included 5473 OHCA-cases (68.8 years, 69.9% men) and matched them to 20 866 non-OHCA-controls. Compared with no use of non-cardiac QT-drugs, drugs of both categories were associated with increased OHCA-risk, but seemingly weaker for category 2 {category 1: case 3.2%, control 1.4%, ORadj 1.7 [95% confidence interval (CI): 1.3-2.1]}; [category 2: case 7.3%, control 4.0%, ORadj 1.4 (95% CI: 1.2-1.6)]. The increased risk occurred in men and women, at all ages (highest in patients aged ≤50 years), and both in the presence or absence of cardiovascular drug use.CONCLUSION: Both category 1 and category 2 QT-drugs are associated with increased OHCA-risk in both sexes, at all ages, and in patients taking or not taking cardiovascular drugs.
AB - AIM: Drugs causing QT-prolongation as off-target effect [non-cardiac QT-prolonging drugs (QT-drugs)] increase the risk of out-of-hospital cardiac arrest (OHCA). Such drugs are categorized in multiple clinically widely used CredibleMeds.org lists. Category 1 ('known risk of Torsade de Pointes') and category 2 ('possible risk of Torsade de Pointes') are of particular clinical relevance. However, a category-stratified analysis of OHCA-risk is presently unavailable.METHODS AND RESULTS: We conducted a case-control study with OHCA-cases from presumed cardiac causes included from the ARREST registry in the Netherlands (2009-2018) that was specifically designed to study OHCA, and age/sex/OHCA-date matched non-OHCA-controls. Adjusted odds ratios for OHCA (ORadj) of QT-drugs from categories 1 or 2 were calculated, using conditional logistic regression. Stratified analysis was performed according to sex, age, and presence of cardiovascular drugs (proxy for cardiovascular disease). We included 5473 OHCA-cases (68.8 years, 69.9% men) and matched them to 20 866 non-OHCA-controls. Compared with no use of non-cardiac QT-drugs, drugs of both categories were associated with increased OHCA-risk, but seemingly weaker for category 2 {category 1: case 3.2%, control 1.4%, ORadj 1.7 [95% confidence interval (CI): 1.3-2.1]}; [category 2: case 7.3%, control 4.0%, ORadj 1.4 (95% CI: 1.2-1.6)]. The increased risk occurred in men and women, at all ages (highest in patients aged ≤50 years), and both in the presence or absence of cardiovascular drug use.CONCLUSION: Both category 1 and category 2 QT-drugs are associated with increased OHCA-risk in both sexes, at all ages, and in patients taking or not taking cardiovascular drugs.
KW - Cardiovascular Agents/adverse effects
KW - Case-Control Studies
KW - Female
KW - Humans
KW - Long QT Syndrome/chemically induced
KW - Male
KW - Middle Aged
KW - Out-of-Hospital Cardiac Arrest/chemically induced
KW - Risk Factors
KW - Torsades de Pointes/chemically induced
UR - http://www.scopus.com/inward/record.url?scp=85128819592&partnerID=8YFLogxK
U2 - 10.1093/europace/euab251
DO - 10.1093/europace/euab251
M3 - Journal article
C2 - 34661653
SN - 1099-5129
VL - 24
SP - 630
EP - 638
JO - Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology
JF - Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology
IS - 4
ER -