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. 2021 Apr 2:12:631869.
doi: 10.3389/fimmu.2021.631869. eCollection 2021.

Hydroxychloroquine Does Not Increase the Risk of Cardiac Arrhythmia in Common Rheumatic Diseases: A Nationwide Population-Based Cohort Study

Affiliations

Hydroxychloroquine Does Not Increase the Risk of Cardiac Arrhythmia in Common Rheumatic Diseases: A Nationwide Population-Based Cohort Study

Chien-Hsien Lo et al. Front Immunol. .

Abstract

Objectives: Hydroxychloroquine (HCQ) is widely used to treat rheumatic diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS). Cardiac arrhythmia has been concerned as important safety issue for HCQ. The aim of this study was to investigate whether hydroxychloroquine increases new-onset arrhythmia among patients with RA, SLE or SS.

Methods: This was a retrospective cohort study that conducted from the longitudinal health insurance database of Taiwan. Patients with newly diagnosed RA, SLE or SS with age ≥20 years old were selected from 2000 to 2012. Patients who received HCQ and without HCQ treatment groups were matched by propensity score to minimize the effect of selection bias and confounders. The Cox proportional hazard model was used to analyze the risk of arrhythmia between the two groups after controlling for related variables.

Results: A total of 15892 patients were selected to participate and finally 3575 patients were enrolled in each group after matching. There was no different risk of all arrhythmia in patients using HCQ than without HCQ (adjusted hazards ratio 0.81, 95% CI 0.61-1.07) and ventricular arrhythmia as well. The incidence of arrhythmia did not increase when HCQ co-administrated with macrolides. The arrhythmia risk was also not different regardless of daily HCQ dose <400mg or ≥400mg or follow-up duration of ≦4 months or >4 months.

Conclusion: The administration of HCQ did not increase the risk of all cardiac arrhythmia and ventricular arrhythmia regardless of different duration of treatment (≦4 months or >4 months) or cumulative dose (<400mg or ≥400mg) in patients with common autoimmune diseases such as RA, SLE and SS.

Keywords: Hydroxychloroquine; Sjögren's syndrome; arrhythmia; rheumatoid arthritis; systemic lupus erythematosus.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow chart of patient selection for those with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) or Sjögren’s syndrome (SS), who were using hydroxychloroquine (HCQ) (study group) and or not using HCQ (non-HCQ control group) from the National Health Insurance Research Database.
Figure 2
Figure 2
The cumulative incidence of all cardiac arrhythmia (A) and ventricular tachyarrhythmia (B) between the hydroxychloroquine (HCQ) group and the non-HCQ group (p-value=0.165 and p-value=0.548 respectively, Log-rank test).
Figure 3
Figure 3
Subgroup analysis using the Cox proportional hazard model for the association between arrhythmia and HCQ. HR, hazard ratio; HCQ, hydroxychloroquine.
Figure 4
Figure 4
The risk of arrhythmias in the subgroup analysis of individual diseases and those with different daily HCQ doses and follow-up durations. aHR, adjusted hazard ratio; HCQ, hydroxychloroquine.

References

    1. Ben-Zvi I, Kivity S, Langevitz P, Shoenfeld Y. Hydroxychloroquine: from malaria to autoimmunity. Clin Rev Allergy Immunol (2012) 42:145–53. 10.1007/s12016-010-8243-x - DOI - PMC - PubMed
    1. Alarcon GS, McGwin G, Bertoli AM, Fessler BJ, Calvo-Alen J, Bastian HM, et al. . Effect of hydroxychloroquine on the survival of patients with systemic lupus erythematosus: data from LUMINA, a multiethnic US cohort (LUMINA L). Ann Rheum Dis (2007) 66:1168–72. 10.1136/ard.2006.068676 - DOI - PMC - PubMed
    1. Group CHS. A randomized study of the effect of withdrawing hydroxychloroquine sulfate in systemic lupus erythematosus. N Engl J Med (1991) 324:150–4. 10.1056/NEJM199101173240303 - DOI - PubMed
    1. Rempenault C, Combe B, Barnetche T, Gaujoux-Viala C, Lukas C, Morel J, et al. . Metabolic and cardiovascular benefits of hydroxychloroquine in patients with rheumatoid arthritis: a systematic review and meta-analysis. Ann Rheum Dis (2018) 77:98–103. 10.1136/annrheumdis-2017-211836 - DOI - PubMed
    1. Wang SQ, Zhang LW, Wei P, Hua H. Is hydroxychloroquine effective in treating primary Sjogren’s syndrome: a systematic review and meta-analysis. BMC Musculoskelet Disord (2017) 18:186. 10.1186/s12891-017-1543-z - DOI - PMC - PubMed

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