Evidence for cardiac safety and antiarrhythmic potential of chloroquine in systemic lupus erythematosus.
OBJECTIVE
To perform a comprehensive evaluation of heart rhythm disorders and the influence of disease/therapy factors in a large systemic lupus erythematosus (SLE) cohort.


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.
Pacemaker Clinic, Heart Institute (InCor), University of São Paulo Medical School, FMUSP, Avenue Dr Enéas de Carvalho Aguiar 44, 05403-900-São Paulo, Brazil ricardo.alkmim@incor.usp.br.
Ricardo Alkmim
RA
Teixeira
Rheumatology Division, University of São Paulo Medical School, FMUSP, Av. Dr. Arnaldo, 455 - 3o Floor/Room 3190, 01246-903 - São Paulo, Brazil.
Eduardo F
EF
Borba
Pacemaker Clinic, Heart Institute (InCor), University of São Paulo Medical School, FMUSP, Avenue Dr Enéas de Carvalho Aguiar 44, 05403-900-São Paulo, Brazil.
Anísio
A
Pedrosa
Pacemaker Clinic, Heart Institute (InCor), University of São Paulo Medical School, FMUSP, Avenue Dr Enéas de Carvalho Aguiar 44, 05403-900-São Paulo, Brazil.
Silvana
S
Nishioka
Rheumatology Division, University of São Paulo Medical School, FMUSP, Av. Dr. Arnaldo, 455 - 3o Floor/Room 3190, 01246-903 - São Paulo, Brazil.
Vilma S T
VS
Viana
Pacemaker Clinic, Heart Institute (InCor), University of São Paulo Medical School, FMUSP, Avenue Dr Enéas de Carvalho Aguiar 44, 05403-900-São Paulo, Brazil.
José A
JA
Ramires
Pacemaker Clinic, Heart Institute (InCor), University of São Paulo Medical School, FMUSP, Avenue Dr Enéas de Carvalho Aguiar 44, 05403-900-São Paulo, Brazil.
Roberto
R
Kalil-Filho
Rheumatology Division, University of São Paulo Medical School, FMUSP, Av. Dr. Arnaldo, 455 - 3o Floor/Room 3190, 01246-903 - São Paulo, Brazil.
Eloísa
E
Bonfá
Pacemaker Clinic, Heart Institute (InCor), University of São Paulo Medical School, FMUSP, Avenue Dr Enéas de Carvalho Aguiar 44, 05403-900-São Paulo, Brazil.
Martino
M
Martinelli Filho
D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D001938:Brazil / Q000453:epidemiology; D002316:Cardiotonic Agents / Q000627:therapeutic use; D015984:Causality; D002738:Chloroquine / Q000627:therapeutic use*; D015897:Comorbidity; D004562:Electrocardiography / Q000187:drug effects / Q000706:statistics & numerical data; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D056687:Off-Label Use; D015995:Prevalence; D012189:Retrospective Studies; D018570:Risk Assessment; D016896:Treatment Outcome
D000889:Anti-Arrhythmia Agents; D018501:Antirheumatic Agents; D002316:Cardiotonic Agents; D002738:Chloroquine
Antimalarial; Arrhythmia; Safety; Systemic lupus erythematosus; Treatment