Hydroxychloroquine in Hospitalized Patients with COVID-19: Real-World Experience Assessing Mortality

Abstract

Introduction: Hydroxychloroquine (HCQ) for coronavirus disease 2019 (COVID-19) is presently being used off-label or within a clinical trial.

Objectives: We investigated a multinational database of patients with COVID-19 with real-world data containing outcomes and their relationship to HCQ use. The primary outcome was all-cause mortality within 30 days of follow-up.

Methods: This was a retrospective cohort study of patients receiving HCQ within 48 hours of hospital admission. Medications, preexisting conditions, clinical measures on admission, and outcomes were recorded.

Results: Among patients with a diagnosis of COVID-19 in our propensity-matched cohort, the mean ages ± SD were 62.3 ± 15.9 years (53.7% male) and 61.9 ± 16.0 years (53.0% male) in the HCQ and no-HCQ groups, respectively. There was no difference in overall 30-day mortality between the HCQ and no-HCQ groups (HCQ 13.1%, n=367; no HCQ 13.6%, n=367; odds ratio 0.95, 95% confidence interval 0.62-1.46) after propensity matching. Although statistically insignificant, the HCQ-azithromycin (AZ) group had an overall mortality rate of 14.6% (n=199) compared with propensity-matched no-HCQ-AZ cohort's rate of 12.1% (n=199, OR 1.24, 95% CI 0.70-2.22). Importantly, however, there was no trend in this cohort's overall mortality/arrhythmogenesis outcome (HCQ-AZ 17.1%, no HCQ-no AZ 17.1%; OR 1.0, 95% CI 0.6-1.7).

Conclusions: We report from a large retrospective multinational database analysis of COVID-19 outcomes with HCQ and overall mortality in hospitalized patients. There was no statistically significant increase in mortality and mortality-arrhythmia with HCQ or HCQ-AZ.

Keywords: Antimalarial; azithromycin; coronavirus; hydroxychloroquine; macrolide; severe acute respiratory syndrome coronavirus 2.

Figure 1

(a) Kaplan‐Meier survival analysis of the study groups before propensity‐score matching: HCQ and no HCQ (unmatched mortality). (b) Kaplan‐Meier survival analysis of the study groups after propensity‐score matching. Variables used for propensity matching included hypertension, diabetes mellitus, chronic obstructive lung disease, heart failure, obesity, nicotine dependence, and history of stroke (HCQ and no HCQ [matched mortality]). (c) Kaplan‐Meier survival in propensity‐matched patients with mortality‐arrhythmia outcome. Variables used for propensity matching included hypertension, diabetes mellitus, chronic obstructive lung disease, heart failure, obesity, nicotine dependence, and history of stroke (HCQ and no HCQ [matched mortality‐arrhythmia]). (d) Kaplan‐Meier survival in propensity‐matched patients with bleeding outcome. Variables used for propensity matching included hypertension, diabetes mellitus, chronic obstructive lung disease, heart failure, obesity, nicotine dependence, and history of stroke (HCQ and no HCQ [matched bleeding]). HCQ = hydroxychloroquine.

Figure 2

(a) Kaplan‐Meier survival analysis of the study groups before propensity‐score matching: HCQ + AZ and no HCQ + no AZ (unmatched mortality). (b) Kaplan‐Meier survival analysis of the study groups after propensity‐score matching. Variables used for propensity matching included hypertension, diabetes mellitus, chronic obstructive lung disease, heart failure, obesity, nicotine dependence, and history of stroke (HCQ + AZ and no HCQ + no AZ [matched mortality]). (c) Kaplan‐Meier survival in propensity‐matched patients with mortality‐arrhythmia outcome. Variables used for propensity matching included hypertension, diabetes mellitus, chronic obstructive lung disease, heart failure, obesity, nicotine dependence, and history of stroke (HCQ + AZ and no HCQ + no AZ [matched mortality‐arrhythmia]). (d) Kaplan‐Meier survival in propensity‐matched patients with bleeding outcome. Variables used for propensity matching included hypertension, diabetes mellitus, chronic obstructive lung disease, heart failure, obesity, nicotine dependence, and history of stroke (HCQ + AZ and no HCQ + no AZ [matched bleeding]). AZ = azithromycin; HCQ = hydroxychloroquine.