Table 3.
Antimalarial treatment for COVID-19 and cardiovascular-related safety outcomes.
| Study | Design | Country | Sample size, Population | Antimalarial dosing | Comparator | Cardiovascular-related Safety Outcomes | Main Results |
|---|---|---|---|---|---|---|---|
| Borba et al. | RCT | Brazil | 81 (62/81 with confirmed COVID-19 infection) |
HCQ 600 mg twice daily for 10 days (AND AZT 500 mg daily for 5 days in ARDS) |
HCQ 450 mg twice daily on day 1, then daily for 4 days (AND AZT 500 mg daily for 5 days in ARDS) |
ECG on day 13 and 28 | QTc was greater than 500 msec in 18.9% of the high-dosage group and in 11.1% of the low-dosage group (p = 0.51) |
| Mercuro et al. | Cohort | USA | 90 hospitalized with pneumonia | HCQ 400 mg twice on day 1, then 400 mg daily for 4 days AND AZT (dose and duration unknown) |
Only HCQ | QTc prolongation | Combination HCQ + AZT therapy was associated with a greater change in QTc compared with HCQ alone (p = 0.03) QTc was greater than 500 msec in 19% of the HCQ group and in 21% of the HCQ+AZT group |
| Rosenberg et al. | Cohort | USA | 1438 hospitalized | HCQ + AZT/HCQ alone/AZT alone; Dose and duration unknown |
Supportive treatment | - Cardiac arrest (secondary outcome) - QTc prolongation (secondary outcome) |
There was a significant association with cardiac arrest in the HCQ + AZT group (OR 2.13, 95% CI 1.12–4.05) but not in the HCQ-alone group (OR 1.91, 95% CI 0.96–3.81) There was no significant difference in abnormal ECG findings (27.1% in the HCQ + AZT group, 27.3% in the HCQ-alone group, 16.1% in the AZT-alone group, and 15% in the supportive treatment group) |
| Ramireddy et al. | Case series | USA | 98 hospitalized with confirmed COVID-19 or clinical suspicion for COVID-19 | HCQ 400 mg twice on day 1, then 200 mg twice daily for 4 days + AZT 500 mg for 5 days |
ECGs prior to CQ treatment | Prolonged QTc | Critical QTc prolongation was observed in 12% of the patients |
| Chorin et al. | Case series | USA | 84 hospitalized | HCQ and AZT; Dose and duration unknown |
ECGs prior to CQ treatment | Prolonged QTc | QTc prolongation was observed in 11% of the patients |
| Saleh et al. | Cohort | USA | 201 hospitalized | CQ 500 mg twice on day 1, then 500 mg daily for 4 days AND/OR HCQ 400 mg twice daily on day 1, then 200 mg twice daily for 4 days + AZT 500 mg daily for 5 days |
ECGs prior to CQ treatment | - QTc prolongation - Torsades de pointes |
QTc prolongation was observed in 9% of the patients; Torsades de pointes was not observed |
| Bessiere et al. | Case series | France | 40 ICU patients | HCQ 200 mg twice daily for 10 days | ECGs prior to CQ treatment | Prolonged QTc | QTc prolongation was observed in 36% of the patients |
| van den Broek et al. | Case series | The Netherlands | 95 suspected hospitalized | CQ 600 mg loading dose, then 300 mg twice daily for 4 days |
ECGs prior to CQ treatment | Prolonged QTc | QTc prolongation was observed in 23% of the patients |
| Cipriani et al. | Case series | Italy | 126 hospitalized | HCQ 200 mg twice daily for 3 or more days AND AZT 500 mg daily for 3 or more days |
ECGs prior to CQ treatment | Prolonged QTc | There was no significant difference in QTc interval duration between post-treatment results (450 msec) and pre-treatment results (426 msec) (p = 0.02) |
Abbreviations: HCQ: Hydroxychloroquine; CQ: Chloroquine; AZT: Azithromycin; RR: Relative Risk; OR: Odds Ratio; HR: Hazard Ratio; CI: Confidence Interval; ICU: intensive care unit; PCR: polymerase chain reaction; QTc: QT corrected; ECG: electrocardiogram.