Hydroxychloroquine-Chloroquine, QT-Prolongation, and Major Adverse Cardiac Events: A Meta-analysis and Scoping Review.

Abstract

We aimed to evaluate the high-quality literature on the frequency and nature of major adverse cardiac events (MACE) associated with either hydroxychloroquine (HCQ) or chloroquine (CQ). We searched Medline, Embase, International Pharmaceutical Abstracts, and Cochrane Central from 1996 onward using search strategies created in collaboration with medical science librarians. Randomized controlled trials (RCTs) published in English language from January 1996 to September 2022, involving adult patients at least 18 years of age, were selected. Outcomes of interest were death, arrhythmias, syncope, and seizures. Random-effects meta-analyses were performed with a Treatment Arm Continuity Correction for single and double zero event studies. By study drug, there were 31 HCQ RCTs (n = 6677), 9 CQ RCTs (n = 622), and 1 combined HCQ-CQ trial (n = 105). Mortality was the most commonly reported MACE at 220 of 255 events (86.3%), with no reports of torsades de pointes or sudden cardiac death. There was no increased risk of MACE with exposure to HCQ-CQ compared with control (risk ratio [RR] = 0.90, 95% CI = 0.69-1.17, I2 = 0%). These findings have important implications with respect to patient reassurance and updated guidance for prescribing practices of these medications. Despite listing as QT-prolonging meds, HCQ-CQ did not increase the risk of MACE.