Three Studies Add To Evidence For Safety Of RAAS Inhibitors In COVID-19 Pandemic

Three new observational studies are adding to the growing body of evidence that patients receiving renin-angiotensin-aldosterone system (RAAS) inhibitors do not face a higher risk of death or serious illness from COVID-19.

"Their message is consistent—none of the three studies showed evidence of harm" if patients continue taking the important drugs, said a team led by Dr. John Jarcho, a deputy editor at the New England Journal of Medicine, where the studies appear online.

There had been concern about angiotensin-converting-enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) because animal studies have shown that the novel coronavirus, designated SARS-CoV-2, latches onto the ACE2 receptor floating on the surface of healthy cells. Some media outlets and websites have turned that hypothetical problem into a dire warning about the drugs, even though discontinuing them could be dangerous.

"Taken together, these three studies do not provide evidence to support the hypothesis that ACE inhibitor or ARB use is associated with the risk of SARS-CoV-2, the risk of severe COVID-19 among the infected, or the risk of in-hospital death among those with the positive test," the Jarcho team concluded in their editorial.

One study involved 6,272 patients with confirmed disease from the Lombardy region of Italy. A team led by Dr. Giuseppe Mancia of the University of Milano-Bicocca found that although more COVID-19 patients were taking one of the drugs, it was "because of their higher prevalence of cardiovascular disease. However, there was no evidence that ACE inhibitors and ARBs affected the risk of COVID-19."

A second study, this one involving 12,594 patients, 5,894 of whom tested positive for COVID-19, looked for any risk posed by the two classes of drugs plus beta-blockers, thiazide diuretics, and calcium-channel blockers.

"We found no substantial increase in the likelihood of a positive test for COVID-19 or in the risk of severe COVID-19 among patients who tested positive in association with five common classes of antihypertensive medications," said that team, led by Dr. Harmony Reynolds of New York University's Grossman School of Medicine.

The study with the largest COVID-19 population—8,910 cases in 11 countries—found that patients on an ACE inhibitor were actually less likely to die, with an odds ratio of 0.33, compared with patients not on the drug.

"Among medications, ACE inhibitors and statins were more commonly used by survivors than by nonsurvivors, whereas no association between survival and the use of ARBs was found," said the research team, led by Dr. Mandeep Mehra of Brigham and Women's Hospital's Heart and Vascular Center.

ARBs posed an additional death risk of 23%, but that was not statistically significant.

That third study also concluded that already having heart failure, coronary artery disease, and chronic obstructive pulmonary disease (COPD) posed some of the highest risks for patients infected with the novel coronavirus, more than doubling their odds of death.

Specifically, with COPD the risk of death was nearly triple compared to patients without the condition.

The findings are derived from an observational database developed from the efforts of 169 hospitals in North America, Asia and Europe. The study included patients admitted through March 15.

In all, 5.8% died in the hospital.

Death rates for individual risk factors were:

• 15.3% with heart failure, which was 2.48 times higher than for patients without heart failure;
• 14.2% among COVID-19 sufferers with chronic obstructive pulmonary disease, or 2.96 times greater than patients without COPD;
• 11.5% when patients had cardiac arrhythmia, 1.95 times greater than for those with a normal heart rhythm;
• 10.2% for patients with coronary artery disease, or 2.7 times higher than for those without it;
• 10% for patients over 65, which was 93% higher compared with younger patients; and
• 9.4% for smokers, up 79% compared with former smokers and nonsmokers.

As with the Reynolds study, death rates were not influenced by the use of other medicines such as beta blockers, antiplatelet therapies, statins, or insulin.

"Our results also suggest that women are proportionately more likely than men to survive the infection," the Mehra team said, noting earlier research showing that "Women have stronger innate and adaptive immunity and greater resistance to viral infections than men."

—Gene Emery

Source