Key result
Bedaquiline causes QTcF >500 ms in ~4% of drug-resistant TB patients without causing arrhythmias.
Why the study?
Bedaquiline has a black-box warning for arrhythmias and sudden death, but the incidence of QTc prolongation and cardiac events under programmatic conditions was unclear.
Does bedaquiline treatment cause significant QTc prolongation or cardiac events in patients with drug-resistant tuberculosis?
Cohort (n=420)
No
Does bedaquiline treatment cause significant QTc prolongation or cardiac events in patients with drug-resistant tuberculosis?
Bedaquiline treatment for drug-resistant tuberculosis is associated with modest QTcF prolongation but no recorded arrhythmias or cardiac deaths, suggesting a manageable cardiac safety profile under programmatic conditions.
Supports bedaquiline use with QTc monitoring in resistant TB; extends observational safety data but leaves randomized confirmation open.
Background Bedaquiline has a black-box warning of the risk of arrhythmias and sudden death. This study aimed to determine the incidence of QTc prolongation and cardiac events in patients receiving bedaquiline for drug-resistant tuberculosis (DR-TB) under programmatic conditions. Methods Retrospective cohort study of patients receiving bedaquiline at a DR-TB hospital in KwaZulu Natal, South Africa from September 2017 to February 2019. The primary outcome, a prolonged QT interval corrected using the Fridericia formula (QTcF), was defined as QTcF >500 ms, QTcF change >60 ms from baseline, or both. Results Among 420 patients (66.2% male, median age 36 years), the median QTcF was 406.4 (interquartile range [IQR], 389.1–421.3) ms at baseline, increasing to 430.5 (IQR, 414.4–445.1) ms by 3 months and 434.0 (IQR, 419.0–447.9) ms at 6 months. Eighteen of 420 patients (4.3%) had a QTcF >500 ms and 110 of 420 patients (26.2%) had a QTcF change >60 ms. There were no recorded arrhythmias or cardiac deaths. Odds of prolonged QTcF were increased with concomitant azoles (adjusted odds ratio [aOR], 5.61 [95% confidence interval (CI), 2.26–13.91]; P < .001) and an inverse association with HIV-positive status (aOR, 0.34 [95% CI, .15–.75]; P = .008) and hypertension (aOR, 0.13 [95% CI, .02–.86]; P = .02). After prolongation, the QTcF declined to <500 ms, whether drugs were interrupted or not. Conclusions We observed a modest prolongation of QTcF, maximal at week 15; there were no recorded arrhythmias or related deaths.
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Isralls et al. (2021) conducted a cohort in drug-resistant tuberculosis (DR-TB) (n=420). Bedaquiline was evaluated on Prolonged QT interval corrected using the Fridericia formula (QTcF), defined as QTcF >500 ms, QTcF change >60 ms from baseline, or both. Bedaquiline treatment for drug-resistant tuberculosis resulted in a QTcF >500 ms in 4.3% of patients and a change >60 ms in 26.2%, with no recorded arrhythmias or related deaths.
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