Evidence for cardiac safety and antiarrhythmic potential of chloroquine in systemic lupus erythematosus

Abstract

Aims: To perform a comprehensive evaluation of heart rhythm disorders and the influence of disease/therapy factors in a large systemic lupus erythematosus (SLE) cohort.

Methods and results: Three hundred and seventeen consecutive patients of an ongoing electronic database protocol were evaluated by resting electrocardiogram and 142 were randomly selected for 24 h Holter monitoring for arrhythmia and conduction disturbances. The mean age was 40.2 ± 12.1 years and disease duration was 11.4 ± 8.1 years. Chloroquine (CQ) therapy was identified in 69.7% with a mean use of 8.5 ± 6.7 years. Electrocardiogram abnormalities were detected in 66 patients (20.8%): prolonged QTc/QTd (14.2%); bundle-branch block (2.5%); and atrioventricular block (AVB) (1.6%). Age was associated with AVB (P = 0.029) and prolonged QTc/QTd (P = 0.039) whereas anti-Ro/SS-A and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores were not (P > 0.05). Chloroquine was negatively associated with AVB (P = 0.01) as was its longer use (6.1 ± 6.9 vs. 1.0 ± 2.5 years, P = 0.018). Time of CQ use was related with the absence of AVB [odds ratio (OR) = 0.103; 95% confidence interval (CI) = 0.011-0.934, P = 0.043] in multiple logistic regression. Holter monitoring revealed abnormalities in 121 patients (85.2%): supraventricular ectopies (63.4%) and tachyarrhythmia (18.3%); ventricular ectopies (45.8%). Atrial tachycardia/fibrillation (AT/AF) were associated with shorter CQ duration (7.05 ± 7.99 vs. 3.63 ± 5.02 years, P = 0.043) with a trend to less CQ use (P = 0.054), and older age (P < 0.001). Predictors of AT/AF in multiple logistic regression were age (OR = 1.115; 95% CI = 1.059-1.174, P < 0.001) and anti-Ro/SS-A (OR = 0.172; 95% CI = 0.047-0.629, P = 0.008).

Conclusions: Chloroquine seems to play a protective role in the unexpected high rate of cardiac arrhythmias and conduction disturbances observed in SLE. Further studies are necessary to determine if this antiarrhythmic effect is due to the disease control or a direct effect of the drug.

Keywords: Antimalarial; Arrhythmia; Safety; Systemic lupus erythematosus; Treatment.