Tag: ACE inhibitors

Long-term Use of RAS Inhibitor Drugs Could Damage Kidneys

Photo by Robina Weermeijer on Unsplash

New research is raising concerns that long-term use of renin-angiotensin system (RAS) inhibitor drugs such as ACE inhibitors could be contributing to kidney damage.

The researchers stress that patients should continue taking the medications. But the scientists are urging studies to better understand the drugs’ long-term effects.

“Our studies show that renin-producing cells are responsible for the damage. We are now focusing on understanding how these cells, which are so important to defend us from drops in blood pressure and maintain our well-being, undergo such transformation and induce kidney damage,” said UVA’s Dr Maria Luisa Sequeira Lopez. “What is needed is to identify what substances these cells make that lead to uncontrolled vessel growth.”

A billion people around the world are affected by chronic hypertension. In a study published in JCI Insight, University of Virginia (UVA) researchers were seeking to better understand why severe forms of the condition are often accompanied by atherosclerosis in the kidney, leading to organ damage.

They found that renin cells, which help regulate blood pressure through renin production, play an important role. Harmful changes in the renin cells can cause the cells to invade the walls of the kidney’s blood vessels. The renin cells then trigger a buildup of another cell type, smooth muscle cells, that cause the vessels to thicken and stiffen, resulting in impeded kidney blood flow.

Long-term use of RAS inhibitor drugs, such as ACE inhibitors, or angiotensin receptor blockers, have a similar effect. But the study found that long-term use of the drugs was associated with hardened kidney vessels in both lab mice and humans

The researchers note that the medications can be lifesaving for patients, so they stress the importance of continuing to take them. But they say additional studies are needed to better understand the drugs’ long-term effects on the kidneys.

“It would be important to conduct prospective, randomised controlled studies to determine the extent of functional and tissue damage in patients taking medications for blood pressure control,” said UVA’s Dr Ariel Gomez. “It is imperative to find out what molecules these cells make so that we can counteract them to prevent the damage while the hypertension is treated with the current drugs available today.”

Source: University of Virginia

ACE Inhibitors Reduce Immune Defence against Bacteria

Neutrophil interacting with two pink-colored, rod shaped, multidrug-resistant (MDR), Klebsiella pneumoniae
Neutrophil interacting with two pink-colored, rod shaped, multidrug-resistant (MDR), Klebsiella pneumoniae. Photo by CDC on Unsplash

Scientists have found evidence suggesting that giving patients ACE inhibitors reduces the ability of their immune system to resist bacterial infections.  the group describes testing of multiple ACE inhibitors in mice and human cells.

ACE inhibitors are typically given to patients with hypertension, and some instances to people with heart failure, kidney disease or diabetes. The drugs relaxes the walls of arteries, veins and capillaries, reducing blood pressure. Some prior studies had shown that the drugs also help the immune system by boosting neutrophils, which are produced to fight bacteria. In this new study, published in the journal Science Translational Medicine, the researchers have found the opposite to be true.

In order to see the effects of ACE inhibitors on the immune system, researchers at Cedars-Sinai Medical Center administered different brands of ACE inhibitor such as Zestril and Altace, to mice and then tested their ability to resist bacterial infections. Compared to untreated mice, those with the ACE inhibitors had greater difficulty in recovering from bacterial infections such as staph.

Seven human patients who were taking an ACE inhibitor volunteered blood samples to measure their immune response. The researchers found that the neutrophils were unable to produce the molecules needed to fight off bacteria. They were also found to be in vitro ineffective against bacteria.

The researchers also tested another drug used to treat hypertension, an angiotensin II receptor drug, Cozaar. These drugs work by preventing arterial walls from constricting, which reduces blood pressure. They found no evidence of a negative impact on immunity. They did not test beta-blockers, which work by preventing adrenergic receptors from being stimulated, reducing cardiac action.

The researchers concluded that administering ACE inhibitors to patients puts them at an increased risk of bacterial infections, noting that doctors may want to try alternative drugs to treat their patients.

Source: MedicalXpress

Journal information: Duo-Yao Cao et al, An ACE inhibitor reduces bactericidal activity of human neutrophils in vitro and impairs mouse neutrophil activity in vivo, Science Translational Medicine (2021). DOI: 10.1126/scitranslmed.abj2138

ARB Has Slight Edge Over ACE Inhibitors for Hypertension Treatment

Photo by Hush Naidoo on Unsplash

A huge multinational study found that while angiotensin-converting enzyme (ACE) inhibitors are just as effective as angiotensin receptor blockers (ARBs) for hypertension treatment, ARBs have slightly fewer side effects.

The study, led by researchers at Columbia University Vagelos College of Physicians and Surgeons and encompassing millions of electronic health records, is the largest to compare the safety and efficacy of these two types of drugs. The findings were published online in Hypertension.

“Physicians in the United States and Europe overwhelmingly prescribe ACE inhibitors, simply because the drugs have been around longer and tend to be less expensive than ARBs,” said senior study author George Hripcsak, MD, the Vivian Beaumont Allen Professor and chair of biomedical informatics at Columbia University Vagelos College of Physicians and Surgeons.

“But our study shows that ARBs are associated with fewer side effects than ACE inhibitors. The study focused on first-time users of these drugs. If you’re just starting drug therapy for hypertension, you might consider trying an ARB first. If you’re already taking an ACE inhibitor and you’re not having any side effects, there is nothing that we found that would indicate a need for a change.”

“U.S. and European hypertension guidelines list 30 medications from five different drug classes as possible choices, yet there are very few head-to-head studies to help physicians determine which ones are better,” Dr Hripcsak said. “In our research, we are trying to fill in this information gap with real-world observational data.”

ACE inhibitors and ARBs are among the choices, and they have a similar mechanism of action. Both reduce the risk of stroke and heart attacks, though it’s known that ACE inhibitors are associated with increased risk of cough and angioedema.

“We wanted to see if there were any surprises–were both drug classes equally effective, and were ARBs producing any unexpected side effects when used in the real world?” Hripcsak says. “We’re unlikely to see head-to-head clinical trials comparing the two since we are reasonably sure that both are effective.”

To tackle the problem, the researchers analysed insurance claims and electronic health records from approximately 3 million patients in Europe, Korea, and the United States who were starting antihypertensive treatment with either an ACE inhibitor or an ARB.

The researchers employed a variety of cutting-edge mathematical techniques to dramatically reduce the bias and deal with information gaps from electronic health records, balancing the two treatment groups as if they had been enrolled in a prospective study.

The researchers tracked four cardiovascular outcomes–heart attack, heart failure, stroke, and sudden cardiac death–and 51 adverse events in patients after they started antihypertensive treatment.

They found that the vast majority of patients–2.3 million–were prescribed an ACE inhibitor, but found no significant difference between the two drug classes in reducing major cardiovascular complications in people with hypertension. As expected, patients taking ACE inhibitors had a higher risk of cough and angioedema, but the risk of pancreatitis and gastrointestinal bleeding was slightly higher as well.

“Our study largely confirmed that both antihypertensive drug classes are similarly effective, though ARBs may be a little safer than ACE inhibitors,” Hripcsak said. “This provides that extra bit of evidence that may make physicians feel more comfortable about prescribing ARBs versus ACE inhibitors when initiating monotherapy for patients with hypertension. And it shows that large-scale observational studies such as this can offer important insight in choosing among different treatment options in the absence of large randomised clinical trials.”

Source: EurekAlert!