Use of non-recommended drugs in Brugada Syndrome: a Danish nationwide cohort study
Authors: Jespersen CHB , Kroell J , Bhardwaj P , Hansen CJ , Svane J , Winkel B , Joens C , Jacobsen PK , Torp-Pedersen C , Koeber L , Tfelt-Hansen J , Weeke PE 
Published: May 2022

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
To lower the risk of sudden cardiac death, patients with Brugada Syndrome (BrS) are recommended to avoid intake of drugs known to increase the risk of arrhythmias or the development of type-1 BrS ECG. However, information on adherence to these recommendations among patients with BrS is limited.

Purpose
To examine treatment with non-recommended drugs before and after diagnosis with BrS, risk factors of treatment with these drugs, and whether treatment was associated with a higher risk of hospitalization with ventricular arrhythmias or death.

Methods
All patients diagnosed with BrS in Denmark (1995-2018) with &gt;12 months of follow-up were identified through nationwide registries using the ICD-10 diagnosis code DI472M (PPV 95.8%). Relevant BrS risk drugs were identified and grouped as drugs to "avoid" or "preferably avoid" in agreement with the likelihood of promoting arrhythmias and type-1 BrS ECG according to brugadadrugs.org(1) (accessed August 2021). Multiple logistic regression (adjusted for sex, age, year of diagnosis, and relevant comorbidities and drugs) was performed to identify factors associated with risk drug use during follow-up.

Results
We identified 270 patients with BrS. Median age at the time of diagnosis was 46.2 years [IQR 32.6-57.6], 70.4% were male. Before the time of diagnosis, 16 patients (5.9%) were treated with a drug to "avoid" or "preferably avoid" (n=5 and n=12, respectively). During a median follow-up of 79 months, 89 patients (33%) were treated with at least one BrS risk drug after the time of diagnosis (table). A total of 22 patients with BrS (8.1%) received ≥2 different drugs at any time during follow-up. There was no significant difference in proportions of patients receiving a risk drug the year prior to diagnosis (12.2%) compared to each of the five years following diagnosis (year 1-5, respectively: 12.2%; 9.7%; 12.3%; 13.6%; 13.5% (p&gt;0.05 for all)).
Females had an odds ratio (OR) of 2.21 [95% CI 1.21-4.03] for use of risk drugs. Also associated with a greater likelihood of risk drug use after diagnosis were having a psychiatric disease at baseline (OR=4.80 [1.72-13.41]) and any use of a risk drug within 90 days prior to diagnosis (OR=8.54 [2.13-34.31]) (figure).
During follow-up, six patients were hospitalized for ventricular arrhythmias; none had redeemed a prescription of a risk drug. In total, 12 patients died, of which five (41.7%) had redeemed a prescription of one or more risk drugs within 50 days of death.

Conclusions
1/3 patients with BrS received a risk drug at any time point after diagnosis. No change in proportions of patients treated with risk drugs was identified after time of diagnosis. 5/12 patients that died during follow-up had redeemed a prescription of one or more risk drugs within 50 days of death. Female sex, any psychiatric diagnosis, and use of a non-recommended drug before diagnosis with BrS were associated with a greater likelihood of risk drug use after diagnosis.