Clinical paperUse of torsades de pointes risk drugs among patients with out-of-hospital cardiac arrest and likelihood of shockable rhythm and return of spontaneous circulation: A nationwide study
Introduction
Survival after out-of-hospital cardiac arrest (OHCA) has improved over recent years, which is, in part, due to increased awareness and improvements in each step of the “chain of survival”. However, it still remains one of the leading causes of death in developing countries and affects more than half a million patients per year.1., 2. Hence, following that “prevention is better than cure”, heightened focus towards modifiable risk factors (e.g. torsades de pointes [TdP] risk drug use) is empirical if OHCA is to be prevented.
To date, more than 200 commonly prescribed types of medication have been associated with a graded risk of QT prolongation and risk of developing malignant arrhythmias (e.g. TdP) (https://www.Crediblemeds.org).3 A previous study, including 525 patients with presumed cardiac arrest, found an association between use of QT prolonging medication and autopsy-defined causes of sudden death which highlights the importance of identifying patients vulnerable for developing arrhythmia to reduce the risk of cardiac arrest.4 While previous studies have implicated concurrent pharmacotherapy treatment with selected drugs as risk factors of OHCA (e.g. antidepressants, antipsychotics, and non-steroidal anti-inflammatory drugs)5., 6., 7., 8. little is known regarding the overall use of pharmacotherapy with proarrhythmic affects in an OHCA setting and if such use may effect the prognosis including likelihood of presenting with a shockable rhythm at the time of OHCA and subsequent risk of survival.
To address these gaps in current knowledge, the objective of this nationwide study among patients with OHCA of cardiac origin was to determine prevalence of treatment with TdP risk drugs prior to OHCA, identify factors associated with such treatment, and determine if TdP risk drug use modified the OHCA prognosis including associated likelihood of presenting with a shockable rhythm and ROSC.
Section snippets
Registries
In Denmark the government tax-funded single payer healthcare system guarantees unrestricted access to healthcare. All Danish citizens are assigned a unique and permanent identification number, upon birth or immigration, which allows for nationwide cross-linkage among the Danish registries on an individual-level. This study was based on data from the Danish Cardiac Arrest Registry, the Danish National Patient Registry, and the Danish National Prescription Registry.
The Danish Cardiac Arrest
Patient characteristics
For the present study, we identified 27,481 patients with an OHCA of cardiac origin. The median age for patients at the time of OHCA was 72 years (interquartile range [IQR] 62.0, 80.0) and 32.3% were female. Patient characteristics stratified by overall TdP risk drug use 0–30 days before OHCA are listed in Table 1. Notably, TdP risk drug treated patients had a significantly higher burden of comorbidities compared with patients not in treatment with a TdP risk drug including cancer (8.2% and
Discussion
In this nationwide study, we examined the overall use of drugs with proarrhythmic properties (i.e. QT prolongation and/or risk of TdP) prior to OHCA and how use may be associated with shockable rhythm and survival. This study had three main findings. First, use of TdP risk drugs was common among patients with OHCA with more than one third in treatment at the time of OHCA. Second, a significant increase in TdP risk drug use was observed in the time before OHCA. Third, the adjusted logistic
Limitation
Although we tried to eliminate effects of possible confounders, the present study is register based and several limitations should be considered. The study aims to descriptively address the proportion of patients who were in treatment with a TdP risk drug immediately before their OHCA and association between TdP risk drug use and subsequent shockable rhythm and ROSC was done exclusively among patients with OHCA. However, we cannot exclude the risk of confounding by indication or residual
Conclusion
In this nationwide study among patients with OHCA, use of TdP risk drugs was common with 37% of patients in treatment at the time of OHCA with an observed increment in the use of TdP risk drugs in the time immediately preceding OHCA. We found treatment with TdP risk drugs to be associated with lower odds of both the presenting rhythm being shockable and ROSC. Thus, despite that TdP risk drugs are known to be arrhythmogenic, the larger burden of comorbidities among patients in TdP risk drug
Data availability
Due to restrictions related to Danish law and protecting patient privacy, the combined set of data as used in this study can only be made available through a trusted third party, Statistics Denmark. Data will be shared on request to the corresponding author with permission of Statistics Denmark. More information regarding data access is available at https://www.dst.dk/en/TilSalg/Forskningsservice.
Conflict of Interest Statement
The authors declare no conflicts of interest.
CRediT authorship contribution statement
Johanna Krøll: Conceptualization, Methodology, Writing – review & editing. Camilla H.B. Jespersen: Writing – review & editing. Søren Lund Kristensen: Writing – review & editing. Emil L. Fosbøl: Writing – review & editing. Naja Emborg Vinding: Writing – review & editing. Freddy Lippert: Writing – review & editing. Kristian Kragholm: Writing – review & editing. Christian Jøns: Writing – review & editing. Steen M. Hansen: Writing – review & editing. Lars Køber: Writing – review & editing. Peter
Acknowledgements
Dr. Jøns reports honoraria; modest; from Biotronik Inc; speaker/speaker’s bureau; modest Abbott, outside the submitted work. Prof. Køber reports honorarium form Novo, Novartis, AstraZeneca and Boehringer, outside the submitted work. Dr. Hansen is employee at Johnson & Johnson, unrelated to the submitted work. Dr. Kristensen reports honoraria from Astra Zeneca, Boehringer Ingelheim, Novartis, outside the submitted work. Prof. Tfelt-Hansen reports grants from Novo Nordisk Foundation Tandem
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