Background/Purpose: Hydroxychloroquine (HCQ) is a derivative of quinidine, a class 1a anti-arrhythmic agent used to prevent ventricular arrhythmias and recurrent atrial fibrillation (AFib). AFib occurs more commonly in patients with systemic lupus erythematosus (SLE) compared to the general population. HCQ is a cornerstone treatment in SLE. This study examines the association of HCQ use and AFib or ventricular arrhythmias in SLE.

Methods: A retrospective cohort of adult SLE (ICD 10: M32) patients at a tertiary academic rheumatology practice from Dec 1,2014 to May 30,2017 excluding patients with prevalent AFib was constructed. Patients were categorized as HCQ users versus non-users. Primary outcome was incident AFib adjudicated by electronic health record (EHR) review and EKG confirmation. AFib events occurring in the first year of observation were considered prevalent AFib to allow for a run-in period and exclude prevalent cases more reliably. Secondary outcome was incident ventricular arrhythmias- a composite of ventricular tachycardia (VT), ventricular fibrillation (VF), torsades, and sudden cardiac death (SCD)adjudicated similarly. Multivariate regression analysis was performed to estimate the association between HCQ exposure and development of incident AFib, after adjusting for relevant confounders, including demographics (age, sex, ethnicity), AFib‐related co-morbidities (BMI, smoking, alcohol use, chronic obstructive pulmonary disease, obstructive sleep apnea, hypertension, coronary artery disease, heart failure, diabetes, cerebrovascular accident and transient ischemic attack, peripheral vascular disease, thyroid disorder, chronic kidney disease and liver dysfunction), anti-arrhythmic medication use (beta-blockers, calcium channel blockers, flecainide, digoxin, amiodarone), and autoimmune serologies. Sub-group analysis was performed on patients age >65yrs (given higher risk of AFib).

Results: Our study included 1646 patients with SLE including 754 HCQ users. During the observation period, 5 AFib events occurred in HCQ users and 18 in non-users. Unadjusted odds ratio (OR) was calculated at 0.22 (95% CI 0.08-0.60, p=0.003), and multivariable logistic regression analysis showed an OR of 0.33 (95% CI 0.12-0.91, p=0.03) for incident AFib. Six incident ventricular arrhythmia events (2 VT, 3 torsades, 1 SCD) occurred in HCQ users and 3 (2 VT, 1 SCD) occurred in non-users with OR of 2.49 (95% CI 0.62-9.9, p=0.2). In the age>65 yrs sub-group analysis, OR was 0.4 (95% CI 0.13-1.25, p=0.11).

Conclusion: In this exploratory study, HCQ use was associated with a 67% reduced risk of incident AFib in SLE. In light of the cardiovascular risk benefits of HCQ and its close relation to anti-arrhythmic medication quinidine, if our preliminary results are confirmed in larger studies, our findings may be used as rationale for a randomized study of HCQ’s protective role against AFib in high-risk patients with SLE.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/association-of-hydroxychloroquine-use-and-incident-atrial-fibrillation-in-systemic-lupus-erythematosus-a-retrospective-study/