Discussion:
Among patients who were hospitalized for COVID-19, this study showed no
significant association between prior use of ACEI/ARBs and COVID-19
mortality or severity as evident by ICU admission rate after adjusting
for baseline characteristics, comorbidities, and steroid use, using the
adjusted logistic regression model and Cox-proportional hazard model.
The mean BMI in our study population was high (32). Eighty percent of
the patients had BMI equal or higher than 25. This finding correlates
with the findings of other studies on the association between BMI and
COVID-19 hospitalization rates.
Some studies have suggested that ACEI/ARB may increase viral entry, with
concerns that these drugs could increase the risk of developing severe
outcome with COVID-19
However, to date, there is insufficient data the association between
prior use of ACEI/ARBs associated and an increased risk of COVID-19
severity. A retrospective cohort study was conducted in two Saudi public
specialty hospitals, included 354 patients with COVID-19 (in which 146
were ACEI/ARB users and 208 were non-ACEI/ARB users) after controlling
for confounders, using multivariate logistic regression and sensitivity
analyses using propensity score matching (PSM) and inverse propensity
score weighting (IPSW) for high-risk patient subsets. The ACEI/ARB group
had an eight-fold higher risk of developing critical or severe COVID-19
(OR = 8.25, 95%CI = 3.32–20.53); a nearly 7-fold higher risk of
intensive care unit (ICU) admission (OR = 6.76, 95%CI = 2.88–15.89)
and a nearly 5-fold higher risk of requiring noninvasive ventilation (OR
= 4.77,95%CI = 2.15–10.55). Concluding that ACEI/ARBs use was
associated with a higher risk of severe COVID-19 disease. However, this
study had a small sample size, some variables were overlooked including
the use of steroids, and the results showed a wide confidence interval.
On the other hand, a prospective cohort study in England involving
8.28 million participants showed reduced risk of COVID-19 positive
disease requiring hospitalization. This study is limited by
unavailability of standard systematic strategy for COVID-19 testing in
the UK and restricting the COVID-19 testing to only hospitalized
patients by UK health policy during the period of the study.
Despite that, a meta-analysis including 13 studies conducted in 2020
showed that ACEI/ARB use was not associated with an increased risk of
all-cause mortality or severe disease due to COVID-19. Among these 13
studies, 11 studies that reported odds ratio showed the thebACEI/ARB
group had a significantly lower risk of all-cause mortality than
non-ACEI/ARB group regardless of confounders of adjustment for
confounders. This meta-analysis was limited by inconsistencies in the
definition of severe diseases and in inclusion criteria that were
inconsistent across the studies.
In addition to this meta-analysis, an open randomized controlled trial
in Brazil including 659 hospitalized patients with mild to moderate
COVID-19 showed no effect of discontinuation of ACEIs or ARBs on
COVID-19 mortality. However, this study explored a different question
than our study. The two proposed two conflicting hypotheses state that
ARBs and ACEIs either increase ACE2 expression, allowing virus entry
into the cell and, therefore, increasing SARS-COV2 infectivity and
severity or coronavirus downregulates ACE2 receptors causing an
elevation of angiotensin II, which may lead to lung injury. Based on
this, prior use of ACEI/ARB would affect the COVID-19 infectivity,
severity or mortality or than the use of ACEIs/ARBs after establishment
COVID-19.
Another study conducted in New York in the March of 2020 showed a
reduced length of hospital stay in patients admitted with COVID-19 who
used ACEI/ARB in the hospital, most of whom belonged to ethnic
minorities. This limitations of this study include the disproportionate
size of the control vs. treatment group and the fact that study only
considered the ACEIARB during the hospitalization. The results were not
significant for the other primary outcome or the secondary outcomes.
We have a large high-quality database of hospitalized COVID-19 patients
at our hospitals. Our study is observational and we were able to reduce
the confounding effect by adjusting a wide range of confounders recorded
in electronic medical records including age, race, BMI, and other
comorbidities. Our sample was representative and was restricted to a
group of patients with hypertensive. Another great strength of our study
is the inclusion of a diverse group of patients as the eight hospitals
are spread out over the Southeast Michigan region where a majority of
Michigan’s population resides and comprises of Caucasians, African
Americans, and Arabs. The limitations of our study include, the
retrospective nature of the study, the inability to specify the
chronicity of ACEI/ARB use based on the available data, overlooking of
unknown confounders and finally, and performing the study during the
early months of COVID-19 pandemic where little information about the
treatment and disease was available.
At this stage, there is insufficient clinical evidence for either, thus
we still need further studies. Until further data are available, we
should continue using ACEI and ARB to treat cardiovascular disease in
patients with COVID-19 given the significant cardiovascular benefits of
ACEI/ARBs. In addition, the sudden withdrawal of ACEI/ARBs in those
patients may result in adverse outcomes.