Prevalence of ECG testing and characteristics among new hydroxychloroquine and chloroquine users within a multi-center tertiary care center

Abstract

COVID-19 raised concern regarding cardiotoxicity and QTc prolongation of hydroxychloroquine (HCQ) and chloroquine (CQ). We examined the frequency and patient factors associated with ECG testing and the detection of prolonged QTc among new HCQ/CQ users in a large academic medical system. 10,248 subjects with a first HCQ/CQ prescription (1/2015–3/2020) were included. We assessed baseline (1 year prior to and including day of initiation of HCQ/CQ through 2 months after initial HCQ/CQ prescription) and follow-up (10 months after the baseline period) patient characteristics and ECGs obtained from electronic health records. Among 8384 female HCQ/CQ new users, ECGs were obtained for 22.3%, 14.3%, and 7.6%, at baseline, follow, and both periods, respectively. Among 1864 male HCQ/CQ new users, ECGs were obtained more frequently at baseline (29.7%), follow-up (18.0%), and both periods (11.3%). Female HCQ/CQ users with a normal QTc at baseline but prolonged QTc (> 470 ms) at follow-up (13.1%) were older at HCQ/CQ initiation [mean 64.7 (SD 16.5) vs. 58.7 (SD 16.9) years, p = 0.004] and more likely to have history of myocardial infarction (41.0% vs. 21.6%, p = 0.0003) compared to those who had normal baseline and follow-up QTc. The frequency of prolonged QTc development was similar (12.4%) among male HCQ/CQ new users (> 450 ms). Prior to COVID-19, ECG testing before and after HCQ/CQ prescription was infrequent, particularly for females who are disproportionately affected by rheumatic diseases and were just as likely to develop prolonged QTc (> 1/10 new users). Prospective studies are needed to guide future management of HCQ/CQ therapy in rheumatic populations. Supplementary Information The online version contains supplementary material available at 10.1007/s00296-022-05125-0.

Hydroxychloroquine and Chloroquine-Induced Cardiac Arrhythmias and Sudden Cardiac Death in Patients with Systemic Autoimmune Rheumatic Diseases: A Systematic Review and Meta-Analysis

“…The most common study designs were retrospective cohort (n = 19), prospective cohort (n = 6), case-controlled (n = 6), and retrospective observational (including pharmacovigilance; n = 3) (Table 1). 5, Of the 34 studies included, only 11 provided mean QTc and OR for prolonged QTc for metaanalysis (Table 2). Six studies provided the mean QTc difference, and all reported outcomes in HCQ users alone.…”

“…Eighteen studies reported outcomes in populations that pooled rheumatic diseases in the analysis, most commonly RA and SLE. 5, Other diseases reported included unspecified mixed rheumatic disease, systemic sclerosis, undifferentiated connective tissue disease, mixed connective tissue disease, Henoch-Schönlein purpura, urticarial vasculitis, proteinase 3 (PR3) vasculitis, myeloperoxidase (MPO) vasculitis, eosinophilic granulomatosis with polyangiitis, Takayasu arteritis, Behçet's disease, adult-onset Still's disease, polyarteritis nodosa, relapsing polychondritis, calcium pyrophosphate disease, unspecified inflammatory arthritis, Sjögren disease, sarcoidosis, spondyloarthropathy, polymyalgia rheumatica, juvenile idiopathic arthritis, morphea, osteoarthritis, and cutaneous lupus erythematosus. Disease duration and duration of HCQ/CQ therapy were infrequently and inconsistently reported and thus could not be extracted.…”

“…29.5% of HCQ/CQ users and 33.8% of HCQ/CQ nonusers were female. 5, Of studies reporting outcomes in patients with SLE included in the meta-analysis, only 1 reported mean systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K). 40 Most studies (n = 26, 76.5%) reported outcomes among HCQ-users while 6 studies reported outcomes in both HCQ and CQ-users, and only 2 reported outcomes of CQ-users alone.…”

“…The Framingham formula 53 was used in only 2 included studies. 5, Among the 70,609 HCQ and CQ users identified in all included studies, there were 695 events of prolonged QTc and 520 events of prolonged QTc pooled with other conduction abnormalities, 11 events of torsades de pointes, 43 events of QTc prolongation pooled with torsades de pointes (polymorphic ventricular tachycardia), and 120 events of cardiac death. Six hundred ninety-nine events of supraventricular tachycardia, including 631 events of atrial fibrillation or atrial flutter, were identified.…”

“…[1][2][3] HCQ is the only immunomodulatory therapy shown to improve survival in SLE.2 However, concerns regarding HCQ and corrected QT (QTc) interval prolongation arose when HCQ was being considered as possible treatment for COVID-19. 4,5 Although there were many new studies examining HCQ and QTc intervals early in the pandemic, data from patients with COVID-19 should not be extrapolated directly to patients with systemic autoimmune rheumatic diseases as there is evidence of cardiotoxicity due to COVID-19 itself. 6 The HCQ dose, duration, and its combination with azithromycin, another QTc prolonging medication, 3,7,8 for the treatment of COVID-19 is also different than the HCQ regimen for systemic autoimmune rheumatic diseases.…”