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

Offerhaus, Joost A.; Wilde, Arthur A.M.; Remme, Carol Ann

(Hydroxy)chloroquine ((H)CQ) is being investigated as 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 hospital and hence likely already (severely) affected. Another suggested approach employs prophylactic (H)CQ treatment aimed at preventing either SARS-CoV-2 infection or 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 for patients with pre-existing 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) which reduces their repolarization reserve, predisposing them to (H)CQ-induced QT-prolongation, and this may be more relevant in females who already have a longer QT to start with. This review provides an overview of the current evidence on (H)CQ therapy in COVID-19 patients and discusses different strategies for prophylactic (H)CQ therapy (i.e. pre-infection, post-exposure, post-infection). 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 ECG monitoring.