Clinical significance of QT-prolonging drug use in patients with MDR-TB or NTM disease.

Abstract

Many drugs with potential QT prolongation effects (QT drugs) have already been used for decades in patients with multidrug-resistant TB (MDR-TB) or non-tuberculous mycobacterial (NTM) disease, but without a common consensus. To investigate the effects of QT drugs on cardiac events in patients with MDR-TB or NTM disease. We retrospectively reviewed 373 patients (mean age: 56.4 years) with MDR-TB or NTM disease treated for >1 month with clofazimine (CFZ), moxifloxacin (MFX), bedaquiline (BDQ), delamanid (DLM) or macrolides (clarithromycin or azithromycin). Adverse cardiac events, death and QTcF changes were evaluated. Forty-four per cent had MDR-TB; 165 (44%), 315 (85%), 10 (3%), 229 (61%) and 1 patient received CFZ, MFX, BDQ, macrolides and DLM, respectively. Except for three patients (0.8%) lost to follow-up with unknown cause of death, 3 (0.8%, 95%CI 0.2-2.4) adverse cardiac events were documented: atrial fibrillation, cardiac tamponade due to TB pericarditis and cardiac arrest, which was determined to not have been caused by QT drugs. Clinically significant QTcF changes (QTcF > 500 msec or an increase > 60 msec) were observed in 10/60 patients (17%, 95%CI 8.0-30.7) without clinical events. The use of QT drugs, alone or in combination, in the treatment of MDR-TB or NTM disease is relatively safe.