Cardiac Risk Factors in Drug-Resistant Tuberculosis Patients on Bedaquiline: A Retrospective Cohort Study

Bedaquiline improves treatment outcomes in drug-resistant tuberculosis (DR-TB), but prolongs the QT interval; the cardiac safety must be thoroughly evaluated in clinical applications. This study aims to assess the cardiac safety and possible risk factors of bedaquiline-containing regimen in patients with DR-TB.

This retrospective cohort study assessed cardiac safety in 202 patients diagnosed with DR-TB and treated with a bedaquiline-containing regimen between March 2019 and May 2024. Follow-up was conducted from 2nd to 24th weeks after treatment, including cardiovascular-related symptoms, electrocardiogram (ECG) testing, serum electrolyte testing, combined use of medicines, etc. Results: Among 202 participants, 40 (19.80%) patients experienced an absolute change from baseline (ΔQTcF) ≥60 ms (including 1 patient QTcF >500 ms), 4 patients discontinued bedaquiline due to adverse events. QTcF prolongation peaked at the 20th week, and the average QTcF values at each monitoring time point showed significant differences compared to baseline. According to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (Corrected Version 2.1) (DAIDS AE Grading Table, v2.1), 139 (68.81%) had no adverse cardiac events, 18 (8.91%) experienced grade 1-2 events, 44 (21.78%) had grade 3 events, and 1 (0.5%) developed grade 4 events. No heart failure cases or deaths were reported. Over 1,022.7 person-months of follow-up, 45 patients experienced grade ≥3 cardiac events, corresponding to an incidence rate of 4.40 events per 100 person-months. Compared to regimens without clofazimine, the concomitant use of clofazimine was significantly associated with an increased risk of grade ≥3 cardiac adverse events (OR = 3.66, 95% CI: 1.59-8.39, p = 0.002). Patients who experienced hypokalemia (4 of 202; 1.98%) during treatment showed 24-fold higher odds of grade ≥3 adverse cardiac events compared to those without hypokalemia (OR = 24.77, 95% CI: 2.44-251.78, p = 0.007).

QT interval prolongation is common in patients with DR-TB treated with bedaquiline-containing regimens, but the incidence of discontinuation is low. The concomitant use of clofazimine and the occurrence of hypokalemia during treatment will increase the risk of adverse cardiac events. It is recommended routine electrolyte monitoring, aggressive potassium supplementation, and cautious co-prescription of clofazimine or other QT-prolonging drugs for DR-TB patients on bedaquiline.