Renin–angiotensin–aldosterone system inhibitors and SARS-CoV-2 infection: an analysis from the veteran's affairs healthcare system

• Published in: The American heart journal 2021-10, Vol.240, p.46-57
• Main Authors: Sandhu, Alexander T, Kohsaka, Shun, Lin, Shoutzu, Woo, Christopher Y, Goldstein, Mary K., Heidenreich, Paul A
• Format: Article
• Language: English
• Subjects: Adrenergic beta-Antagonists - therapeutic use; Aged; Aldosterone; Angiotensin; Angiotensin II Type 2 Receptor Blockers; Angiotensin Receptor Antagonists - therapeutic use; Angiotensin-converting enzyme inhibitors; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Antihypertensive Agents - therapeutic use; Beta blockers; Blood pressure; Body mass index; Calcium Channel Blockers - therapeutic use; Case-Control Studies; Chronic infection; Clinical Investigations; Codes; Comorbidity; Confidence Intervals; Coronaviruses; COVID-19; COVID-19 - epidemiology; Demographics; Demography; Diabetes; Diabetes mellitus; Diabetes Mellitus - epidemiology; Disease transmission; Enzyme inhibitors; Enzymes; Ethnicity; Female; Health risks; Heart failure; Hemoglobin; Humans; Hypertension; Hypertension - drug therapy; Infections; Kidney diseases; Laboratories; Male; Middle Aged; Odds Ratio; Patients; Peptidyl-dipeptidase A; Pharmacy; Population; Propensity Score; Receptors; Receptors, Virus; Renin; Renin-Angiotensin System - drug effects; Respiratory diseases; SARS-CoV-2; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Socioeconomic factors; Sodium Chloride Symporter Inhibitors - therapeutic use; Standard deviation; Therapy; United States - epidemiology; United States Department of Veterans Affairs; Veterans; Veterans - statistics & numerical data; Viral diseases; Vital signs
• ISSN: 0002-8703; 1097-6744
• DOI: 10.1016/j.ahj.2021.06.004

Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are known to impact the functional receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The association between chronic therapy with these medications and infection risk remains unclear. The objective was to determine the association between prior ACEI or ARB therapy and SARS-CoV-2 infection among patients with hypertension in the U.S. Veteran's Affairs health system. We compared the odds of SARS-CoV-2 infection among three groups: patients treated with ACEI, treated with ARB, or treated with alternate first-line anti-hypertensives without ACEI/ARB. We excluded patients with alternate indications for ACEI or ARB therapy. We performed an augmented inverse propensity weighted analysis with adjustment for demographics, region, comorbidities, vitals, and laboratory values. Among 1,724,723 patients with treated hypertension, 659,180 were treated with ACEI, 310,651 with ARB, and 754,892 with neither. Before weighting, patients treated with ACEI or ARB were more likely to be diabetic and use more anti-hypertensives. There were 13,278 SARS-CoV-2 infections (0.8%) between February 12, 2020 and August 19, 2020. Patients treated with ACEI had lower odds of SARS-CoV-2 infection (odds ratio [OR] 0.93; 95% CI: 0.89-0.97) while those treated with ARB had similar odds (OR 1.02; 95% CI: 0.96-1.07) compared with patients treated with alternate first-line anti-hypertensives without ACEI/ARB. In falsification analyses, patients on ACEI did not have a difference in their odds of unrelated outcomes. Our results suggest the safety of continuing ACEI and ARB therapy. The association between ACEI therapy and lower odds of SARS-CoV-2 infection requires further investigation.