Table 2.
Risk of adverse cardiac effects with usage of hydroxychloroquine in COVID-19 patients
| Author (year, study design) | Population | Key findings | Study limitations |
|---|---|---|---|
|
Asli et al. [157] (2020, Case report) |
1 patient given HCQ | Developed prolonged QTc interval and a right bundle block | Single patient |
|
Borba et al. [114] (2020, Randomized double-blinded parallel phase IIb trial) |
Total = 81 High dose (600 mg CQ BD for 10 days) group = 41 Low dose group (450 mg BD on day 1 and OD for 4 days) = 40 |
Arrhythmias with high dose CQ within 2–3 days of administration, while 11 patients died on the 6th day. Increased mortality in high-dose group in comparison to low-dose group (39% vs. 15%). More instance of a prolonged QTc interval (> 500 ms) in high-dose group—18.9%, than the low-dose group [11.1%]. Ventricular arrhythmia in 2 patients (2.7%) | Limited sample size. Only hospitalized patients with severe SARS-CoV-2 infection |
|
Chorin et al. [158] (2020, Retrospective cohort study) |
251 patients Given HCQ in conjunct to AZT | Development of prolonged QTc (> 500 ms) in 23% of patients with one presenting as polymorphic ventricular tachycardia that was suspected as torsades de pointes | No comparison group |
|
Mahévas et al. [159] (2020, Comparative observational study) |
181 hospitalized patients on supplemental oxygen HCQ group = 84 Non HCQ group = 89 |
No difference in survival rates between patients receiving HCQ with those not being treated by HCQ (89% vs 91%). 10% in HCQ group had adverse changes in ECGs due to which HCQ had to be withdrawn. ECG changes included QTc prolongation (> 60 ms in 7 patients and > 500 ms in 1 patient), first degree AV block in 1 patient and left bundle branch block in 1 patient | Potential confounders since treatment was not given randomly. Only hospitalized patients considered |
|
Mercuro et al. [160] (2020, Retrospective cohort study) |
Total = 90 53: HCQ + AZT 37: HCQ only |
Demonstrated the prolongation of QTc (> 500 ms in 7 patients and > 50 ms in 3 patients). One case of torsades de pointes was also reported | Attributable risk unclear: Most had a pre-existing CVD. No control group |
|
Shirazi et al. [46] (2020, Case series) |
3 patients given HCQ along with lopinavir/ritonavir and other regimens | Sudden cardiac death in all three patients. (It is suggested that the cardiac arrest was due to the proarrythmatic effects of HCQ which along with liponavir/ritonavir could have led to QTc prolongation and development of TdP) | ECG of patients prior to death was not available to confirm the hypothesis. Small sample size |
|
Bessière et al. [161] (2020, Retrospective cohort study) |
40 patients given HCQ and AZT vs HCQ only | 93% patients showed an increase in QTc interval; however, the prolongation was greater in the group receiving HCQ + AZT as compared to HCQ only (33% vs 5%) | Treatment was stopped in most patients before completion |
|
Lane JCE et al. [162] (2020, Cohort self-controlled case series) |
Total = 1,941,802 956,374 and 310,350 users of hydroxychloroquine + sulfasalazine 323,122 and 351,956 users of hydroxychloroquine–azithromycin and hydroxychloroquine–amoxicillin |
Higher risk of 30-day cardiovascular mortality upon using HCQ along with AZT in comparison to HCQ alone | No control arm without HCQ |
|
Saleh et al. [163] (2020, Prospective observational study) |
201 patients given HCQ + AZT | Patients had increased rates of QTc prolongation when used in combination,, however, no case of torsades de pointes was noted | No control arm with HCQ alone or without HCQ |