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COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

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Etiology Zhang X, Yu J, Pan LY, et al. ACEI/ARB use and risk of infection or severity or mortality of COVID-19: A systematic review and meta-analysis. Pharmacol Res. 2020 Aug;158:104927. doi: 10.1016/j.phrs.2020.104927. Epub 2020 May 15.

The effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on the risk of COVID-19 infection and disease progression are yet to be investigated. The relationship between ACEI/ARB use and COVID-19 infection was systematically reviewed. To identify relevant studies that met predetermined inclusion criteria, unrestricted searches of the PubMed, Embase, and Cochrane Library databases were conducted. The search strategy included clinical date published until May 9, 2020. Twelve articles involving more than 19,000 COVID-19 cases were included. To estimate overall risk, random-effects models were adopted. Our results showed that ACEI/ARB exposure was not associated with a higher risk of COVID-19 infection (OR = 0.99; 95 % CI, 0-1.04; P = 0.672). Among those with COVID-19 infection, ACEI/ARB exposure was also not associated with a higher risk of having severe infection (OR = 0.98; 95 % CI, 0.87-1.09; P = 0.69) or mortality (OR = 0.73, 95 %CI, 0.5-1.07; P = 0.111). However, ACEI/ARB exposure was associated with a lower risk of mortality compared to those on non-ACEI/ARB antihypertensive drugs (OR = 0.48, 95 % CI, 0.29-0.81; P = 0.006). In conclusion, current evidence did not confirm the concern that ACEI/ARB exposure is harmful in patientswith COVID-19 infection. This study supports the current guidelines that discourage discontinuation of ACEIs or ARBs in COVID-19 patients and the setting of the COVID-19 pandemic.

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

Cardiology rater

Unfortunately, some speculation has produced big concerns about treating COVID patients with ACEi/ARB. This confirms that in clinical practice these drugs are not dangerous.

Family Medicine (FM)/General Practice (GP) rater

Treatment of Hypertesion is a normal deision in Primary Care. In conclusion, the results of the meta-analysis suggest that use of ACEI/ARB in patients with COVID-19 does not increase the risk of COVID-19 infection, severity, or mortality. However, a lower risk of mortality was observed among those patients who were taking ACEI/ ARB for the treatment of hypertension, looking at more than 19,000 cases. This is a good meta-analysis to decide on treatment changes.

Hospital Doctor/Hospitalists rater

Since we are living in the pandemic era, every relevant piece of information is very useful for the COVID-19 storm!

Infectious Disease rater

These are reassuring data that ACEI/ARB are not harmful for patients with COVID-19. Thus, ACEI/ARB should not be stopped in this setting; particularly if the indication for their use was hypertension.

Infectious Disease rater

Well done meta-analysis.

Infectious Disease rater

This systematic review shows that patients taking ACE inhibitors or ARB are not at increased risk for COVID-19 infection, or of a more serious outcome. On the contrary, the data suggest taking these drugs may be associated with lower mortality rates for COVID-19 infection.

Intensivist/Critical Care rater

There was initial concern about the use of ACE inhibitors or Angiotensin receptor blockers in COVID infection because of the initial association between mortality and hypertension as a comorbidity and the identification of the ACE 2 receptor as the binding site of the virus. As with many associations, they turn out to not be related by cause and effect as this study shows. The authors performed a metaanalysis with over 19,000 patients and found that there was not an increased risk of developing the disease or having more severe disease as was initially hypothesized. The authors did, however, use a random effects model which is conservative at avoiding a type 1 error and is recommended for therapeutic interventions. A fixed effects model would not have changed the result, however, because of the lower OR. A compelling finding, however, is that the OR for the mortality was 0.48. There is a separate trial evaluating these medications as possible therapeutic agents.

Internal Medicine rater

Unfortunately for these authors (and for reasons that are not their fault), they have included the Mehra MR article, responsible for 14 and 22% of their data, which was just retracted for data irregularities yesterday (6/4/20). So until this data is re-run, I think this work is not of further interest to my hospital colleagues.

Public Health rater

The authors included 5 case-control and 7 cohort studies; there were no RCTs. The authors did not include confounders in their review. They did an excellent job stating the limitations of their review: 1. Such as the residual number of unknown confounders. Previous studies reported sex, age, smoking, diabetes which greatly affect the prognosis of COVID-19 infection. However, these potential confounders are considered in most included studies. 2. There are a small number of eligible high-quality studies. 3. The measurement of ACEI/ARB exposure was through medical record review, which is less reliable than other methods. 4. Mild heterogeneity was observed in the analysis of COVID-19 severity. The existence of clinical heterogeneity is expected to lead to a degree of statistical heterogeneity in the results. The definitions of COVID-19 severity and outcomes were inconsistent among the included studies. Finally, the results of this review are susceptible to selection bias given that most of the patients in the study population were in a hospital.