To the Editor:
We read with great interest the review by Khan et al. who discussed the
emerging role of cardiovascular disease and the progression of the novel
Coronavirus disease 19 (COVID-19).1 As part of their
review, the authors discussed a broad range of cardiovascular effects
being observed during and post infection in this disease. We commend
their conclusions that appropriate triage and risk stratification is
essential in patients with cardiovascular disease (CVD) and COVID-19. We
encourage the need for further evidence regarding the mechanisms of CVD
and particularly the use of therapeutics. This is of particular
importance given the global concern about the use of
renin-angiotensin-aldosterone system (RAAS) inhibitors in the mechanisms
of severe acute respiratory distress syndrome coronavirus 2
(SARS-CoV-2).
SARS-CoV-2 utilises the Angiotensin converting enzyme 2 (ACE2) cell
membrane protein on lung alveolar epithelial cells to enter host
cells.1 This ACE2 enzyme is key in the cascade of the
(RAAS) so the authors highlight of the importance understanding this
further was justified. RAAS inhibitors contributing to increased
severity of COVID-19, most commonly in hypertension, is a logical
hypothesis due to their mode of action. However, it is currently unclear
whether this virus’s interaction with ACE2 causes dysregulation or
interference of downstream effectors. Early observational studies
concluded that use of RAAS inhibitors may not be associated with
SARS-CoV-2 infection, or more severe Covid-19 progression. One
retrospective multi-centre study with 1128 participants (188 on a RAAS
inhibitor) suggested that in hospitalised COVID-19 patients with
pre-existing hypertension, RAAS inhibitors had better outcomes compared
with non-RAAS inhibitoruse.2 This supports continuing
their use if already prescribed but recognises the significant risk for
confounding variables in their methodology.2
Discontinuing these medications may potentially put patients at greater
risk of complications, directly due to SARS-CoV-2 infection or
indirectly from a period of blood pressure instability and attenuating
their known cardio- and renal-protective effects.3Furthermore, the authors highlighted that cardiovascular complications
and myocardial injury have also been observed peri- and post-infection
with SARS-CoV-2, even in patients without pre-existing
CVD1. Given these mechanisms are yet to be elucidated
and likely to be multifactorial, this further supports this notion.
We support the conclusion made that there is currently limited evidence
to recommend their use should be discontinued prophylactically and in
confirmed cases.3,4 It is pivotal further pre-clinical
studies are carried out to understand the cardiovascular mechanisms in
COVID-19. We emphasise the need to elucidate mechanisms of RAAS
inhibitors in SARS-CoV-2 infection. Robust and collaborative human
studies are needed to apply this understanding in a meaningful way,
where major confounding variables, such as advancing age, can be
accounted for.
References
- Khan, I.H., Zahra, S.A., Zaim, S., Harky, A., 2020. At the heart of
COVID-19. J Card Surg. 1-2.
- Zhang, P., Zhu, L., Cai, J., Lei, F., Qin, J.-J., Xie, J., Liu, Y.-M.,
Zhao, Y.-C., Huang, Xuewei, Lin, L., Xia, M., Chen, M.-M., Cheng, X.,
Zhang, X., Guo, D., Peng, Y., Ji, Y.-X., Chen, J., She, Z.-G., Wang,
Y., Xu, Q., Tan, R., Wang, H., Lin, J., Luo, P., Fu, S., Cai, H., Ye,
P., Xiao, B., Mao, W., Liu, L., Yan, Y., Liu, M., Chen, M., Zhang,
X.-J., Wang, X., Touyz, R.M., Xia, J., Zhang, B.-H., Huang, Xiaodong,
Yuan, Y., Rohit, L., Liu, P.P., Li, H., 2020. Association of Inpatient
Use of Angiotensin Converting Enzyme Inhibitors and Angiotensin II
Receptor Blockers with Mortality Among Patients With Hypertension
Hospitalized With COVID-19. Circulation Research.
- Jarcho, J.A., Ingelfinger, J.R., Hamel, M.B., D’Agostino, R.B.,
Harrington, D.P., 2020. Inhibitors of the
Renin–Angiotensin–Aldosterone System and Covid-19. N Engl J Med
NEJMe2012924.
- Khashkhusha, T.R., Chan, J.S.K., Harky, A., 2020. ACE inhibitors and
COVID-19: We don’t know yet. J Card Surg.