Frequency of Long QT in Patients with SARS-CoV-2 Infection Treated with Hydroxychloroquine: a Meta-analysis

Abstract

Introduction: Hydroxychloroquine (HCQ) has been proposed as a SARS-CoV-2 treatment but the frequency of long QT (LQT) during use is unknown. Objective: To conduct a meta-analysis of the frequency of LQT in patients with SARS-CoV-2 infection treated with HCQ. Data Sources: PubMed, EMBASE, Google Scholar, the Cochrane Database of Systematic Reviews and preprint servers (medRxiv, Research Square) were searched for studies published between December 2019 and June 30, 2020. Methods: Effect statistics were pooled using random effects. The quality of observational studies and randomized controlled trials was appraised with STROBE and the Cochrane Risk of Bias Assessment tools, respectively. Outcomes: Critical LQT was defined as: (1) maximum QT corrected (QTc)≥500 ms (if QRS<120 ms) or QTc≥550 ms (if QRS≥120 ms), and (2) QTc increase ≥60 ms. Results: In the 28 studies included (n=9124), the frequency of LQT during HCQ treatment was 6.7% (95% confidence interval [CI]: 3.7-10.2). In 20 studies (n=7825), patients were also taking other QT-prolonging drugs. The frequency of LQT in the other 8 studies (n=1299) was 1.7% (95% CI: 0.3-3.9). Twenty studies (n=6869) reported HCQ discontinuation due to LQT, with a frequency of 3.7% (95% CI: 1.5-6.6). The frequency of ventricular arrhythmias during HCQ treatment was 1.68% (127/7539) and that of arrhythmogenic death was 0.69% (39/5648). Torsades de Pointes occurred in 0.06% (3/5066). Patients aged >60 years were at highest risk of HCQ-associated LQT (P<0.001). Conclusions: HCQ-associated cardiotoxicity in SARS-CoV-2 patients is uncommon but requires ECG monitoring, particularly in those aged >60 years and/or taking other QT-prolonging drugs.