Journal article

View all Respiratory Digests

Renin–Angiotensin–Aldosterone System Inhibitors in Patients with Covid-19

Author(s): Vaduganathan M, Vardeny O, Michel T et al

NEJM March 30, 2020

Respiratory infections
General respiratory patient care
Public health

Digest Author(s): Stylianos Loukides, e-Learning Director / 4 April, 2020

The renin–angiotensin–aldosterone system (RAAS) is an elegant cascade of vasoactive peptides that orchestrate key processes in human physiology. COVID-19 pandemic is currently affecting more than 1000000 while >50000 deaths have been reported. There is a considerable evidence that Arterial Hypertension (AH) represents a significant co-morbidity among patients with Covid-19 infection. AH was more frequent in critically ill patients being admitted to the intensive care unit, received mechanical ventilation, or died than among patients who have had mild illness. Some initial thoughts supported that the medical management of Hypertension with RAAS inhibitors, may have contributed to the adverse health outcomes observed. However, the co-existing advancing age was the strongest predictor of Covid-19–related death. Laboratory data supports that any interaction between the SARS viruses and ACE2, potentially enhance infectivity. The above pathophysiological interaction lead to a hypothesis that any use of RAAS inhibitors which alter the ACE2 expression may be partially contribute to what we call disease progression.

This perspective approach raised some important points as following:

  • ACE2, an enzyme that physiologically counters RAAS activation, is the functional receptor to SARS-CoV-2, the virus responsible for the Covid-19 pandemic.
  • Preclinical studies have suggested that RAAS inhibitors may increase ACE2 expression, raising concerns regarding their safety in patients with Covid-19
  • At the moment we consider the above data as Insufficient.
  • Clinical trials are under way to test the safety and efficacy of RAAS modulators, including recombinant human ACE2 and the ARB losartan in Covid-19.
  • Withdrawal of RAAS inhibitors without strong evidence in high-risk patients is not recommended.
  • RAAS inhibitors should be continued in patients with clear indications.

    Comment

    Considering the above speculation we have to address the position of European Cardiology society which was published on line on 13-3-2020. The Council on Hypertension of the European Society of Cardiology wish to highlight the lack of any evidence supporting harmful effect of ACE-I and ARB in the context of the pandemic COVID-19 outbreak. The Council on Hypertension strongly recommends that physicians and patients should continue treatment with their usual anti-hypertensive therapy because there is no clinical or scientific evidence to suggest that treatment with ACEi or ARBs should be discontinued because of the Covid-19 infection. Switching from a RAAS inhibitor to another antihypertensive therapy in a stable patient will require a more close follow -up in order to keep his blood pressure in stable values. However in an infected patient this may worsen an underlying condition which will also indirectly impact the infection prognosis. We cannot exclude the harmful effects, but we need more supportive and clinical evidence.