Renin-Angiotensin System Blockers and Adverse Outcomes of Influenza and Pneumonia: A Danish Cohort Study

J Am Heart Assoc. 2020 Oct 20;9(19):e017297. doi: 10.1161/JAHA.120.017297. Epub 2020 Oct 1.


Background Angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) may worsen the prognosis of coronavirus disease 2019, but any association could be confounded by the cardiometabolic conditions indicating ACE-I/ARB use. We therefore examined the impact of ACE-Is/ARBs on respiratory tract infection outcomes. Methods and Results This cohort study included all adult patients hospitalized with influenza or pneumonia from 2005 to 2018 in Denmark using population-based medical databases. Thirty-day mortality and risk of admission to the intensive care unit in ACE-Is/ARBs users was compared with nonusers and with users of calcium channel blockers. We used propensity scores to handle confounding and computed propensity score-weighted risks, risk differences (RDs), and risk ratios (RRs). Of 568 019 patients hospitalized with influenza or pneumonia, 100 278 were ACE-I/ARB users and 37 961 were users of calcium channel blockers. In propensity score-weighted analyses, ACE-I/ARB users had marginally lower 30-day mortality than users of calcium channel blockers (13.9% versus 14.5%; RD, -0.6%; 95% CI, -1.0 to -0.1; RR, 0.96; 95% CI, 0.93-0.99), and a lower risk of admission to the intensive care unit (8.0% versus 9.6%; RD, -1.6%; 95% CI, -2.0 to -1.2; RR, 0.83; 95% CI, 0.80-0.87). Compared with nonusers, current ACE-I/ARB users had lower mortality (RD, -2.4%; 95% CI, -2.8 to -2.0; RR, 0.85; 95% CI, 0.83-0.87), but similar risk of admission to the intensive care unit (RD, 0.4%; 95% CI, 0.0-0.7; RR, 1.04; 95% CI, 1.00-1.09). Conclusions Among patients with influenza or pneumonia, ACE-I/ARB users had no increased risk of admission to the intensive care unit and slightly reduced mortality after controlling for confounding.

Keywords: angiotensin receptor blockers; angiotensin‐converting enzyme inhibitor; cohort study; infectious disease; intensive care unit.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiotensin Receptor Antagonists / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Betacoronavirus*
  • COVID-19
  • Coronavirus Infections / drug therapy*
  • Denmark / epidemiology
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Influenza, Human / drug therapy*
  • Influenza, Human / epidemiology
  • Male
  • Odds Ratio
  • Pandemics
  • Pneumonia / drug therapy*
  • Pneumonia / epidemiology
  • Pneumonia, Viral / drug therapy*
  • Propensity Score
  • Renin-Angiotensin System / drug effects*
  • Retrospective Studies
  • SARS-CoV-2
  • Survival Rate / trends


  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors