Good things come in threes (and sometimes fours): Update on renin–angiotensin–aldosterone system inhibitors and COVID-19

Since the publication of our article in CMAJ,1 there have been substantial developments in the literature regarding the role of renin–angiotensin–aldosterone system (RAAS) inhibitors in patients with coronavirus disease 2019 (COVID-19). We wish to summarize them here to support our recommendations on prescribing practices for these drugs.

Three large observational studies of more than 20 000 patients with COVID-19 found no association between the use of RAAS inhibitors and increased risk of infection, development of severe disease or death.2^–4 The 3 studies used different methodological approaches, and all came to similar conclusions.

A different cohort study of 18 472 patients who were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) also found no association between RAAS inhibitor use and testing positive for COVID-19. However, a secondary analysis of 1735 patients in the study with confirmed COVID-19 showed an increased risk of severe disease requiring admission to the intensive care unit in patients using RAAS inhibitors.5

All observational studies are at risk of unmeasured confounding. However, according to the results across these studies, RAAS inhibitors are unlikely to cause harm in patients with COVID-19.

In our original article, we reinforced recommendations from multiple professional societies that “the totality of current clinical and experimental evidence for RAAS inhibitors to facilitate infection by SARS-CoV-2 or increase the risk of harm in patients with COVID-19 is insufficient to suggest altering current use.”1 We continue to support this view. Patients prescribed RAAS inhibitors should remain on them during the COVID-19 pandemic, pending release of high-quality and replicable data to the contrary.