Prophylactic (hydroxy)chloroquine in COVID-19: Potential relevance for cardiac arrhythmia risk

Abstract

(Hydroxy)chloroquine ((H)CQ) is being investigated as a treatment for COVID-19, but studies have so far demonstrated either no or a small benefit. However, these studies have been mostly performed in patients admitted to the hospital and hence likely already (severely) affected. Another suggested approach uses prophylactic (H)CQ treatment aimed at preventing either severe acute respiratory syndrome coronavirus 2 infection or the development of disease. A substantial number of clinical trials are planned or underway aimed at assessing the prophylactic benefit of (H)CQ. However, (H)CQ may lead to QT prolongation and potentially induce life-threatening arrhythmias. This may be of particular relevance to patients with preexisting cardiovascular disease and those taking other QT-prolonging drugs. In addition, it is known that a certain percentage of the population carries genetic variant(s) that reduces their repolarization reserve, predisposing them to (H)CQ-induced QT prolongation, and this may be more relevant to female patients who already have a longer QT interval to start with. This review provides an overview of the current evidence on (H)CQ therapy in patients with COVID-19 and discusses different strategies for prophylactic (H)CQ therapy (ie, preinfection, postexposure, and postinfection). In particular, the potential cardiac effects, including QT prolongation and arrhythmias, will be addressed. Based on these insights, recommendations will be presented as to which preventive measures should be taken when giving (H)CQ prophylactically, including electrocardiographic monitoring.

Keywords: Arrhythmia; COVID-19; Chloroquine; ECG; Hydroxychloroquine; Prophylaxis; QT; Recommendations; SARS-CoV-2; Torsades de pointes.

Figure 1

Baseline corrected QT (QTc) interval in the population with coronavirus disease 2019 (COVID-19) compared to the control population. Manually measured QTc values were used unless unavailable or unspecified; the latter are indicated by a red outline., , Error bars indicate standard deviations of each separate study (not available for 2 studies^23,29). The filled symbols (circles and squares) represent the sample size of the studies (see inset color scale). The horizontal black line indicates the overall mean value of all the studies for each group.

Figure 2

Overview of (sub)trials listed on ClinicalTrials.gov assessing the prophylactic use of (hydroxy)chloroquine in severe acute respiratory syndrome coronavirus 2. Trials are listed by estimated sample size and prophylaxis strategy. Trials not conducting any electrocardiography (ECG) are depicted in gray, trials conducting baseline ECG in red, and trials conducting baseline and follow-up ECG in green.

Figure 3

Schematic diagram of the recommendations for electrocardiographic (ECG) monitoring during (hydroxy)chloroquine prophylaxis. ∗Individuals at risk are defined as those with a known history of congenital or acquired long QT syndrome, structural heart disease, bradycardia, use of other QT-prolonging drugs, and conditions with an increased risk of electrolyte disorders (such as chronic diarrhea or chronic kidney disease). ^†Symptom education for patients, ensuring awareness of potential arrhythmic symptoms (eg, dizziness, syncope, and palpitations). QTc = corrected QT.