COVID-19 and Renin Angiotensin Blockers

Authors:
Messerli FH, Siontis GC, Rexhaj E.
Citation:
COVID-19 and Renin Angiotensin Blockers: Current Evidence and Recommendations. Circulation 2020;Apr 13:[Epub ahead of print].

The following are key perspectives from this Viewpoint on COVID-19 and renin angiotensin blockers:

  1. Both angiotensin II converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) have repeatedly, but not consistently, been documented to slow progression of pulmonary complications in vulnerable patients.
  2. These seemingly beneficial findings of renin angiotensin system (RAS) blockade on outcomes in pneumonia resurfaced in the recent literature in relation to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
  3. Epidemiologic data suggest that patients with cardiovascular disease (CVD) and hypertension are more susceptible to SARS-CoV-2 infection and that the course of pneumonia is more severe in hypertensive relative to normotensive subjects.
  4. SARS-CoV-2, the recently identified strain responsible for the current COVID-19 epidemic, relies on ACE2 protein as a cellular entry receptor by binding with its spike (S) protein, similar to SARS-CoV.
  5. Of note, ACE2 expression protects from lung injury, an action which is down-regulated by binding of SARS-CoV via its spike protein.
  6. Experimentally and in humans, RAS blockade has been shown to up-regulate ACE2 activity, thereby potentially antagonizing some effects of COVID-19.
  7. However, presently, there are no clinical data regarding a favorable effect of RAS blockade on pulmonary outcome in SARS-CoV-2-infected patients.
  8. Conversely, speculation has been put forward that the enhanced ACE2 expression with RAS antagonists might increase the number of binding sites, thereby increasing the odds of infection with SARS-CoV-2.
  9. Of note, the RAS effects among available blockers is markedly different. Direct renin inhibitors (DRIs) has been shown to diminish activity of the RAS and also down-regulate ACE2 in animal models. Thus, with DRIs, RAS blockade and cardiopulmonary protection is maintained, but ACE2 seems to be down-regulated.
  10. Presently, all guidelines recommend continuing ACEI/ARBs in patients diagnosed with COVID- 19 infection. Until the evidence in aggregate becomes firmer (and it will), this viewpoint recommends the following regarding COVID-19 and RAS blockade:
    • In noninfected patients and patients at risk, there is currently no valid reason to discontinue RAS blockade;
    • In healthy subjects at risk, evidence is not (yet?) sufficient to prophylactically recommend RAS blockade;
    • If apprehension about increased infectivity persists, patients on ACEIs or ARBs could temporarily be switched to a DRI;
    • In COVID-19-positive patients on RAS blockers, the drugs should be continued;
    • In febrile patients with pulmonary symptoms on RAS blockers, close monitoring of blood pressure and renal function is advisable; RAS blockers should be discontinued only as clinically indicated.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Lipid Metabolism, Novel Agents, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Hypertension

Keywords: Angiotensin II, Angiotensin Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Blood Pressure, COVID-19, Coronavirus, Heart Failure, Hypertension, Lung Injury, Metabolic Syndrome X, Peptidyl-Dipeptidase A, Primary Prevention, Renin, Renin-Angiotensin System, SARS Virus, Severe Acute Respiratory Syndrome, severe acute respiratory syndrome coronavirus 2, Vascular Diseases


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