COVID-19 and Renin Angiotensin Blockers
- Messerli FH, Siontis GC, Rexhaj E.
- 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:
- 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.
- 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.
- 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.
- 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.
- Of note, ACE2 expression protects from lung injury, an action which is down-regulated by binding of SARS-CoV via its spike protein.
- Experimentally and in humans, RAS blockade has been shown to up-regulate ACE2 activity, thereby potentially antagonizing some effects of COVID-19.
- However, presently, there are no clinical data regarding a favorable effect of RAS blockade on pulmonary outcome in SARS-CoV-2-infected patients.
- 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.
- 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.
- 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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