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Heartbeat: interaction of renin–angiotensin–aldosterone blocking drugs with COVID-19 disease susceptibility and severity
  1. Catherine M Otto
  1. Division of Cardiology, University of Washington, Seattle, WA 98195, USA
  1. Correspondence to Professor Catherine M Otto, Division of Cardiology, University of Washington, Seattle, WA 98195, USA; cmotto{at}

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Angiotensin converting enzyme 2 (ACE2) is the primary receptor for the SARS-CoV-2 virus raising concern that patients with cardiovascular disease being treated with an ACE inhibitor or angiotensin receptor blocker (ARB) drug might have altered ACE2 expression leading to increased risk of COVID-19 infection or a more severe disease course. In this issue of Heart, Hippisley-Cox and colleagues1 addressed this question using routinely collected data in a prospective cohort study in England of 8.28 million participants aged 20–99 years. COVID-19 disease was diagnosed in 19 486 patients and 1286 required treatment in the intensive care unit (ICU). Even after adjustment for confounders, ACE inhibitors were associated with a significantly reduced risk of COVID-19 disease (adjusted HR 0.71, 95% CI 0.67 to 0.74) and no increased risk of ICU care (adjusted HR 0.89, 95% CI 0.75 to 1.06). Similarly, adjusted HRs for ARBs were 0.63 (95% CI 0.59 to 0.67) for COVID-19 disease and 1.02 (95% CI 0.83 to 1.25) for ICU care. However, there were significant interactions with ethnicity for ACE inhibitors and ARB (both p<0.001) for COVID-19 RT-PCR diagnosed disease outcome (table 1).

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Table 1

Adjusted HRs (95% CI) for risk of COVID-19 positive test associated with ACE inhibitor and ARB exposure by ethnic group

In the accompanying editorial, Straw and Witte2 point out that ‘Observational data are challenging to work with, requiring care to avoid the pitfalls of observed and hidden interactions and biases while balancing …

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