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Abstract
Background Hydroxychloroquine (HCQ) is a cornerstone medication for the treatment and management of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and other autoimmune rheumatic diseases. Previous studies have found an association between HCQ use and risk of arrhythmias, however the evidence is limited by small sample sizes and selected populations; additionally, findings have been contradictory. We assessed the risk of arrhythmias among new users of HCQ in newly diagnosed SLE and RA patients.
Methods We used administrative health databases from the entire province of British Columbia, Canada covering January 1997 to March 2015 to identify all patients who met the following criteria: 1) incident SLE or RA; 2) no arrhythmic events or use of anti-arrhythmic medications; and 3) no HCQ use prior to the disease index date. Eligible individuals were separated into HCQ initiator and HCQ non-initiator groups, matched 1:1 by propensity scores using baseline confounders of demographics including presence of SLE or RA disease and duration of disease prior to the index date, comorbidities, other medications, and healthcare utilization. Matching was done within the same calendar year to account for a potential secular trend in HCQ use and risk of arrhythmia. The outcomes assessed were any new arrhythmias, atrial fibrillation, abnormal electrocardiogram including prolonged QT syndrome and conduction disorder, and other unspecified arrhythmias during follow-up. Cox proportional hazard models with death as a competing event were used to assess the association of HCQ initiation and the outcomes.
Results We identified 11,518 HCQ initiators (863 SLE and 10,655 RA patients, mean ± SD age 55.9 ± 15.1 years, 76.1% female) and 11,518 HCQ non-initiators (879 SLE and 10,639 RA patients, mean ± SD age 56.0 ± 16.2 years, 76.4% female) after 1:1 propensity score matching. Over the mean follow-up of eight years, there were 1,610 and 1,646 incident arrhythmias in the HCQ initiator and non-initiator groups, respectively. The crude incidence rates of arrhythmia were 17.5, and 18.1 per 1,000 person-years, respectively. Cumulative risk of incident arrhythmia remained similar for both groups. (figure 1). Adjusted hazard ratio (aHR) of incident arrhythmia from the Cox proportional hazard model for HCQ initiators was 0.99 (95% CI: 0.92-1.06) compared to non-initiators (table 1). The corresponding aHRs for HCQ initiators in subtypes of arrhythmia – atrial fibrillation, abnormal electrocardiogram, and other unspecified arrhythmias were 0.95 (95% CI: 0.84-1.06), 1.04 (95% CI: 0.87-1.26), and 0.96 (95% CI: 0.86-1.08), respectively.
Conclusions There is no increased risk of any type of arrhythmia among new users of HCQ in SLE and RA patients. We believe the results of this large cohort study will add to the confidence with which HCQ can be used in SLE and RA management.
Incident arrhythmias of any type among RA and SLE patients initiating HCQ prescription compared with HCQ non-initiators
Cumulative risk of incident arrhythmias for HCQ initiators and non-initiators over the follow-up time
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