COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

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Etiology Fosbol EL, Butt JH, Ostergaard L, et al. Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use With COVID-19 Diagnosis and Mortality. JAMA. 2020 Jul 14;324(2):168-177. doi: 10.1001/jama.2020.11301.

Importance: It has been hypothesized that angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) may make patients more susceptible to coronavirus disease 2019 (COVID-19) and to worse outcomes through upregulation of the functional receptor of the virus, angiotensin-converting enzyme 2.

Objective: To examine whether use of ACEI/ARBs was associated with COVID-19 diagnosis and worse outcomes in patients with COVID-19.

Design, Setting, and Participants: To examine outcomes among patients with COVID-19, a retrospective cohort study using data from Danish national administrative registries was conducted. Patients with COVID-19 from February 22 to May 4, 2020, were identified using ICD-10 codes and followed up from day of diagnosis to outcome or end of study period (May 4, 2020). To examine susceptibility to COVID-19, a Cox regression model with a nested case-control framework was used to examine the association between use of ACEI/ARBs vs other antihypertensive drugs and the incidence rate of a COVID-19 diagnosis in a cohort of patients with hypertension from February 1 to May 4, 2020.

Exposures: ACEI/ARB use was defined as prescription fillings 6 months prior to the index date.

Main Outcomes and Measures: In the retrospective cohort study, the primary outcome was death, and a secondary outcome was a composite outcome of death or severe COVID-19. In the nested case-control susceptibility analysis, the outcome was COVID-19 diagnosis.

Results: In the retrospective cohort study, 4480 patients with COVID-19 were included (median age, 54.7 years [interquartile range, 40.9-72.0]; 47.9% men). There were 895 users (20.0%) of ACEI/ARBs and 3585 nonusers (80.0%). In the ACEI/ARB group, 18.1% died within 30 days vs 7.3% in the nonuser group, but this association was not significant after adjustment for age, sex, and medical history (adjusted hazard ratio [HR], 0.83 [95% CI, 0.67-1.03]). Death or severe COVID-19 occurred in 31.9% of ACEI/ARB users vs 14.2% of nonusers by 30 days (adjusted HR, 1.04 [95% CI, 0.89-1.23]). In the nested case-control analysis of COVID-19 susceptibility, 571 patients with COVID-19 and prior hypertension (median age, 73.9 years; 54.3% men) were compared with 5710 age- and sex-matched controls with prior hypertension but not COVID-19. Among those with COVID-19, 86.5% used ACEI/ARBs vs 85.4% of controls; ACEI/ARB use compared with other antihypertensive drugs was not significantly associated with higher incidence of COVID-19 (adjusted HR, 1.05 [95% CI, 0.80-1.36]).

Conclusions and Relevance: Prior use of ACEI/ARBs was not significantly associated with COVID-19 diagnosis among patients with hypertension or with mortality or severe disease among patients diagnosed as having COVID-19. These findings do not support discontinuation of ACEI/ARB medications that are clinically indicated in the context of the COVID-19 pandemic.

Discipline / Specialty Area Score
General Internal Medicine-Primary Care(US)
Family Medicine (FM)/General Practice (GP)
Infectious Disease
Public Health
Intensivist/Critical Care
Hospital Doctor/Hospitalists
Internal Medicine
Emergency Medicine
Comments from MORE raters

Emergency Medicine rater

As an emergency physician, this information is unlikely to impact clinical practice.

Emergency Medicine rater

It`s comforting to know that ACE inhibitors do not have to be stopped in patients with Covid.

General Internal Medicine-Primary Care(US) rater

The current COVID-19 pandemic has required clinicians to remain conversant with a number of new and interesting medical developments. One of them involves the question of potential benefit or harm from certain medications such as ACE inhibitors and ARBs. We know now about the SARS2 virus and its affinity for the ACE2 cell surface receptor, particularly on the respiratory epithelium. This study reviewed more than 4000 patients to determine the effect of stopping ACE inhibitors and ARBs to see whether there was an effect on the SARS2 binding to the receptor. No significant difference was noted, indicating that stopping these drugs would be of clinical benefit.

Hospital Doctor/Hospitalists rater

This article underscores the necessity of evaluating propensity-adjusted models rather than raw utilization trends.

Intensivist/Critical Care rater

This has been a question since early in the COVID pandemic (i.e., risk associated with ARBs, ACEI). This large retrospective cohort study with adjustment for potential confounders seems to fairly definitely rule out an increased risk. Although not ground-breaking, I think this is important for readers.

Intensivist/Critical Care rater

Important confirmation of what was already known and shows important associations.

Public Health rater

The potential for bias in non-experimental studies is high. We need to await RCTs for a clearer understanding of any risks/benefits.

Public Health rater

This retrospective cohort study investigated the association of the use of ACEI/ARB and the outcomes of COVID-19 patients and also the susceptibility of COVID-19 in patients using ACEI/ARB. The article is important and reassuring to continue the use of ACEI/ARB for patients with cardiovascular diseases.

Respirology/Pulmonology rater

Although this is a retrospective cohort study, it is a robust study that supports findings by others that, after appropriate adjustment, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers do not increase the more severe outcomes of COVID-19 infection compared with non-users. There was no difference when compared with users of calcium channel blockers. The results suggest that it is hypertension and not the drugs used to treat it that increase the risk for severe COVID-19 infection. I also note that racial distribution was not addressed in this study. It is likely the population studied was highly selected for Northern European ancestry. The findings of the study should be cautiously interpreted when considering other racial and ethnic groups such as African Americans and Hispanics.