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 - Funding Information: 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., and H.L.T.), and the COST Action PARQ (grant agreement no. CA19137) supported by COST (European Cooperation in Science and Technology) (T.E.E., M.T.B., and H.L.T.), 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. and H.L.T.). The ARREST registry is supported by an unconditional grant of 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 decision to publish. Publisher Copyright: © 2021 The Author(s). Published by Oxford University Press on behalf of the European Society of Cardiology.
PY - 2022/4/1
Y1 - 2022/4/1
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 - ESCAPE-NET
KW - Non-cardiac QT-prolonging drugs
KW - Out-of-hospital cardiac arrest
KW - Sudden cardiac arrest
UR - http://www.scopus.com/inward/record.url?scp=85128819592&partnerID=8YFLogxK
U2 - https://doi.org/10.1093/europace/euab251
DO - https://doi.org/10.1093/europace/euab251
M3 - Article
C2 - 34661653
SN - 1099-5129
VL - 24
SP - 630
EP - 638
JO - Europace
JF - Europace
IS - 4
ER -