Risk factors

ACE inhibitors and ARBs associated with better COVID-19 outcomes

Three new studies have allayed fears that ACE inhibitors and Angiotensin Receptor Blockers (ARBs) may increase the risk of severe COVID-19 disease, with some showing they may even be beneficial.

With the coronavirus known to enter cells via binding to the ACE2 receptor it had been thought that ACE inhibitors and ARBs would worsen susceptibility to COVID-19 infection or promote more adverse outcomes by upregulation of the ACE2 receptor.

But an observational study from China has found that in hospitalised COVID-19 patients with hypertension, the use of ACEI/ARB was associated with lower risk of all-cause mortality compared with non-users.

Published in Circulation, the retrospective study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB who were admitted to nine hospitals.

After adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was 58% lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted HR, 0.42; 95% CI, 0.19-0.92; P =0.03).

A propensity score-matched analysis also showed lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted HR, 0.37; 95% CI, 0.15-0.89; P = 0.03).

The use of ACEI/ARB was also associated with lower mortality when compared to use of other antihypertensives (adjusted HR, 0.30; 95%CI, 0.12-0.70; P = 0.01).

The study authors said there was still uncertainty around the mechanisms involved in ACE inhibitor and ARB effects in COVID-19 disease, which may involve hypokalaemia and effects on unopposed Angiotensin II. They also cautioned that their study was not powered to differentiate between ACE inhibitors and ARBs.

“Overall, these findings suggested potential beneficial effects observed with continued use of ACEI/ARB therapy and the possible contribution of RAS activation in the pathogenesis of severity of COVID-19 in patients with hypertension,” they concluded.

And a second study, involving 205 acute inpatients with COVID-19 at two London hospitals, has found that treatment with ACE-inhibitors was associated with a reduced risk of rapidly deteriorating severe disease.

There was a lower rate of death or transfer to a critical care unit within 7 days in patients on an ACE inhibitor (Odds Ratio 0​.​29 (CI 0​.​10-0​.​75, p<0​.0​1), after adjusting for age, gender and comorbidities said clinicians from Kings College Hospital.

“We do not see evidence for ACE inhibitors increasing the short-term severity of COVID-19 disease and patients on treatment with ACE inhibitors should continue these drugs during their COVID-19 illness. A potential beneficial effect needs to be explored as more data becomes available,” they said.

A third study from China published in JAMA Cardiology,  involving 362 patients with hypertension hospitalised with COVID-19 infection in Wuhan, found no difference in severity of the disease, complications, and risk of death in patients who were taking ACEIs/ARBs compared with those not treated with these medications.

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