RAAS Inhibitors in COVID-19: A Signal of Benefit?

Hypertension and the discontinuation of blood pressure-lowering medications were associated with increased mortality in COVID-19, according to data from Wuhan, China.

People with high blood pressure (BP) were more likely to die during COVID-19 hospitalization (4.0% vs 1.1% without hypertension, adjusted HR 2.12, 95% CI 1.17-3.82), as were those with a history of hypertension who were not on antihypertensive medication (7.9% vs 3.2% on medications, adjusted HR 2.17, 95% CI 1.03-4.57).

Between those on renin-angiotensin-aldosterone system (RAAS) inhibitors and peers on other antihypertensives, mortality was similar (2.2% vs 3.6%, adjusted HR 0.85, 95% CI 0.28-2.58), reported Fei Li, MD, PhD, of Xijing Hospital in Xi’an, China, and colleagues in European Heart Journal.

But when data from three other groups in China were pooled in a meta-analysis, RAAS inhibitors — angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) — were associated with significantly lower risk of mortality compared to other BP-lowering drugs (RR 0.65, 95% CI 0.45-0.94).

This is “another paper with the tantalizing suggestion that RAAS inhibition might be effective in decreasing the severity of COVID-19 infection,” Harlan Krumholz, MD, of Yale School of Medicine, told MedPage Today. “We are really at the point where we need some trials to test this hypothesis. Fortunately, as before, there is no indication that these drugs cause harm associated with viral infection.”

It had been suspected that ACE inhibitors and ARBs might worsen the severity and mortality of COVID-19 by increasing expression of the ACE2 enzyme necessary for SARS-CoV-2 viral entry.

Cardiovascular societies maintain that patients with hypertension should continue their usual antihypertensive treatment with RAAS inhibitors.

Continued RAAS inhibition in COVID-19 is important because of the chronic kidney disease (CKD) that commonly accompanies hypertension, and CKD patients may require adequate BP control as part of their renal protection, according to an accompanying editorial by Luis Ruilope, MD, PhD, of Madrid’s Hospital Universitario 12 de Octubre, and colleagues.

“Furthermore, the withdrawal of RAAS blockers in these COVID-19 patients would increase the morbidity and mortality risk given the myocardial damage that may occur in COVID-19,” the editorialists added.

RAAS inhibition can also be helpful for its antithrombotic activity, Ruilope’s group noted. “In fact, hyperinflammation and derangement of the RAAS in COVID-19 could contribute to clinically suspected hypercoagulopathy and microvascular immunothrombosis.”

Li’s team performed a retrospective observational study of all 2,877 consecutive patients admitted to Huoshenshan Hospital from Feb. 5 to March 15 of this year. This emergency specialty field hospital had been built in Wuhan specifically to treat COVID-19.

Average age was around 60 years and over half of the cohort were men.

About 30% of the group had histories of hypertension, with 83.5% of those taking medications (RAAS inhibitors in more than one-quarter). Those on RAAS inhibitors shared similar medical history and baseline BP as those on the other medications.

Patients with hypertension tended to develop more severe or critical COVID-19 and require invasive mechanical ventilation, Li and colleagues reported.

The observational study was inherently limited by the potential for unmeasured confounding, according to the investigators, and stratification of patients by drug class led to groups that were not large enough for definitive comparisons.

In the meantime, the ongoing CORONACION trial is expected to provide crucial information on how people not known to be infected with SARS-CoV-2 fare on various antihypertensive drugs.