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

Christiansen, Christian Fynbo; Heide‐Jørgensen, Uffe; Rasmussen, Thomas Bøjer; Bodilsen, Jacob; Søgaard, Ole Schmeltz; Maeng, Michael; Vistisen, Simon Tilma; Schmidt, Morten; Pottegård, Anton; Lund, Lars Christian; Reilev, Mette; Hallas, Jesper; Johansen, Nanna Borup; Brun, Nikolai Constantin; Sørensen, Henrik Toft; Thomsen, Reimar Wernich

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.