RAS inhibitors and COVID-19 severity in hypertensive patients

By Dr. Liji Thomas, MDApr 23 2020

A new study published in the journal JAMA Cardiology in April 2020 reports that patients with hypertension who are taking medications called ACE inhibitors (ACEI) or ARBs are not at higher risk for death or more severe illness with COVID-19. This conclusion supports current guidelines for the treatment of hypertension during this pandemic.

COVID-19 and ACE2 receptors

Patients with COVID-19 are mostly not very sick and recover after a self-limiting illness. However, in some patients with underlying medical conditions, such as hypertension and diabetes mellitus, the illness becomes severe and may lead to death.

Recently, the discovery has been made that the virus gains entry into the cell via the angiotensin-converting enzyme (ACE) 2 molecule on the cell surface. The virus receptor is, therefore, the ACE2 molecule. This also means that cells that express ACE2 are vulnerable to COVID-19 infection.

Coronaviruses penetrating in human cell. Binding of the coronavirus spike protein(red) to an ACE2 receptor (blue) leads to the penetration of the virus in the cell. 3d rendering. PDB 6VSB, 6ACJ. Image Credit: Juan Gaertner / Shutterstock

On the other hand, ACE inhibitors and angiotensin receptor blockers (ARBs) are vital drugs in the control of high blood pressure and survival after heart attacks. It is not clear whether these drugs alter the levels of ACE2 on the cell surface. Low levels of ACE2 can increase the risk of pulmonary edema and reduced lung function, which can be treated by the administration of recombinant ACE2 or losartan.

Current recommendations from most medical and cardiologic societies advise continuing these drugs if the patients are already on them unless there is another clinical indication to stop them.

The current study aimed to explore the possibility that patients with high blood pressure on ACE inhibitors and ARBs have more severe illness or an increased risk of death with COVID-19 infection. This data will help to determine whether such patients should be switched to other drugs for the control of their blood pressure.

How was the study done?

The researchers included 362 patients with COVID-19 admitted to the Central Hospital, Wuhan, from January 15, 2020, to March 15, 2020, in this retrospective study. All patients were diagnosed by real-time polymerase chain reaction (rt-PCR).

All the patients were classified for the severity of disease (COVID-19 pneumonia) according to accepted criteria. Severe illness includes low oxygen saturation in blood, tachypnea, and lung infiltrates over 50% within 24-48 hours, septic shock, respiratory failure, and multiple organ dysfunction. Patients without any features of severe illness were defined as having a non-severe illness.

Hypertension was defined in this study as having had blood pressure of 140/90 mm Hg or more, or being on antihypertensive medication. About a third of the current study cohort were hypertensive, at 31%. Patients were defined as being on ACEIs/ARBs if they were using them at admission and through their period in hospital.

The researchers were looking for correlation of the use of ACEIs/ARBs with severity of disease and mortality rates, as well as for epidemiological, clinical, and laboratory characteristics of the patients.

What did the study show?

Of the 362 patients in the study, men and women were present in almost equal numbers. Most (72%) of them were above the age of 60 years, and a third of them (32%) were on ACEIs/ARBs.

Approximately one in five of these patients died in hospital. The prevalence of other underlying diseases was similar in both groups. Laboratory tests were similar and included blood counts, tests for inflammation, renal and liver function tests, and biomarkers for ischemic heart disease.

Both groups had equal numbers of patients who developed severe illness, acute respiratory distress syndrome, and mortality rates. Most patients with hypertension were on calcium channel blockers, and there was no correlation between any drug/drugs used to control blood pressure and severity of illness or survival.

Specifically, there was a similar percentage of severe illness and mortality in both groups, those who were on ACEIs/ARBs, and those who were not.

The choice of antihypertensive is sometimes dependent on the other medical conditions the person suffers from. However, even when the subset of patients on these drugs were classified by underlying comorbid condition, such as stroke, heart disease, diabetes, neurological disease, and chronic kidney disease, there was no difference in the incidence of severe COVID-10 symptoms and signs, or of death, in the two groups.

Conclusion

The study thus supports the advice of most professional medical bodies that it is safe to continue ACEIs and jARBs unless there is another good reason to switch to other medications. There were no notable differences between the group on these medications and the control group, except that a higher proportion of the former group had heart disease. However, this observational study must be confirmed by other trials.