Hydroxychloroquine, Azithromycin and Mortality in COVID-19: Meta-Analysis

Quick Takes

  • Treatment with hydroxychloroquine was not associated with reduced mortality in hospitalized patients with COVID-19.
  • Use of combination of hydroxychloroquine and azithromycin was associated with increased mortality in hospitalized patients with COVID-19.

Study Questions:

Is hydroxychloroquine (HCQ) with or without azithromycin (AZI) associated with lower mortality in patients with coronavirus disease 2019 (COVID-19)?

Methods:

The authors conducted a meta-analysis of all studies (randomized and nonrandomized) reporting an association between HCQ with and without AZI and survival in patients with COVID-19. The primary analysis compared survival between patients treated with HCQ and standard of care. Subgroup analyses examined the differences between article type (peer-reviewed vs. unpublished), whether confounding factors were adjusted for, and the impact of dose.

Results:

The authors identified 29 articles meeting the meta-analysis’ inclusion criteria: 25 observational, one nonrandomized, and three randomized studies. Fifteen observational studies and the nonrandomized trial had serious risk of bias, of which 10 were critical. After excluding studies with critical bias, the pooled analysis showed HCQ was not associated with mortality (relative risk [RR], 0.83; 95% confidence interval [CI], 0.65-1.06). The finding was similar when examining randomized trials alone (RR, 1.09; 95% CI, 0.97-1.24) and across subgroup analyses; notably between preprints and published studies. In studies with both HCQ and AZI (n = 7), use of combination therapy was associated with an increase in mortality (RR, 1.27; 95% CI, 1.04-1.54) compared to standard of care.

Conclusions:

HCQ use alone was not associated with mortality in patients with COVID-19, while combination use of HCQ and AZI was associated with increased mortality.

Perspective:

This meta-analysis summarizes the latest findings from studies examining the impact of HCQ and AZI on mortality in patients with COVID-19. Findings are consistent with the prior studies showing no positive impact of HCQ treatment in COVID-19. This meta-analysis delves into subgroup analyses and explores potential sources of heterogeneity, only to circle back to the same conclusions: HCQ is not beneficial in patients with COVID-19, and combination of HCQ and AZI is associated with an increased risk of death. There are limitations, as always, but none to justify continued use or testing of HCQ as a treatment in this patient population. It is time to put this story to rest.

Clinical Topics: Prevention, Novel Agents, Statins

Keywords: Azithromycin, Coronavirus, COVID-19, Hydroxychloroquine, Primary Prevention, Randomized Controlled Trials as Topic, Risk, severe acute respiratory syndrome coronavirus 2, Standard of Care


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