Statins vs kidney disease death risk: Cholesterol-lowering drugs help

  • Statins are a cheap, safety-profiled drug that can reduce the risk of death from cardiovascular events by reducing low-density lipoprotein (LDL) cholesterol, also known as ‘bad’ cholesterol, in the blood.
  • First prescribed to people who had had heart attacks, guidance for statin use is being constantly updated, expanding the number of groups of people who could benefit from taking the drug.
  • A recent trial showed all people with human immunodeficiency virus (HIV) over the age of 40 could benefit from taking a statin.
  • Now, a trial has shown older adults with chronic kidney disease could also benefit.

A statin was the most prescribed drug in the United States in 2020, and guidance is continually being updated recommending the expansion of the use of this type of drug.

Initially prescribed in the late 1980s to people who had had a heart attack to prevent them from having another one, statins provided a way to lower levels of low-density lipoprotein (LDL) cholesterol, also known as “bad” cholesterol. This prevents the hardening and narrowing of the arteries which can lead to high blood pressure.

Previously, the only interventions that had been available to people at greater risk of heart disease had been lifestyle interventions, such as diet and exercise. However, research has since shown that statins are more effective than many lifestyle interventions at lowering LDL cholesterol.

Statins’ effect on cholesterol and health

The maximum safe dose of some statins can reduce LDL cholesterol levels by up to 55% on their own, and potentially further in conjunction with other drugs.

Understanding the role of cholesterol to health is so critical that the Nobel Prize in Physiology or Medicine 1985 was awarded jointly to Michael Brown and Joseph Goldstein “for their discoveries concerning the regulation of cholesterol metabolism.”

A study published in The Lancet in 2002 showed that people who were at high risk of cardiovascular disease had their risk of heart attack and stroke reduced by 25% over 5 years when they took 40 milligrams (mg) of simvastatin daily.

Since the introduction of statins in the late 1980s, their use has been expanded to include more people deemed to be at risk of cardiovascular disease or major cardiovascular events in the next 10 years.

Recently, the REPRIEVE trial reported its results on the impact of statins in people with HIV. Results published in the The Lancet show that the statin pitavastatin lowers the risk of cardiovascular events by 35% in people with HIV.

Campaigners are now calling for guidelines to be updated to outline that all people with HIV over the age of 40 should be offered statins.

Can statins help in kidney disease?

Now, a study published in JAMA Network Open, has shown that older people, mainly men, with chronic kidney disease could benefit from taking statins.

Data on U.S. veterans over the age of 65 was collected from Veterans Affairs, Medicaid and Medicare, focusing on those with moderate chronic kidney disease, stages 3 or 4. The cohort was 99% male and had a mean age of 76.9 when they received a diagnosis of chronic kidney disease.

Researchers analyzed data from 17,609 veterans, and they identified 14,685 individuals with chronic kidney disease but who were not taking statins, and 2,924 with kidney disease who were offered statins. All these participants were followed up for 3.6 years.

Results showed that taking statins reduced overall mortality in veterans with chronic kidney disease by 9%.

While there was also a reduction in the number of major adverse cardiovascular events seen among the group who took statins, this difference was not significant.

How might statins reduce death risk in kidney disease?

The study authors did not speculate over the mechanism underpinning these findings in their paper, but they called for a randomized control trial to investigate the discovery further. This would allow for the collection of data on any side effects and harms caused by the medication to be collected, as these were not in this analysis.

Dr. Barry Sears, a researcher in inflammation and founder of the Inflammation Research Foundation, not involved in the current study, offered a hypothesis to Medical News Today:

“Statins can activate AMPK [the 5′-adenosine monophosphate-activated protein kinase pathway], which is a major controller of inflammation at the molecular level by inhibiting NK-κB activity. This would reduce mortality in any chronic disease associated with inflammation such as chronic kidney disease.“

“The effect on cardiovascular mortality is less than on [chronic kidney disease] mortality,“ he added. “However, statins do have side effects, such as muscle damage and diabetes which may explain the differences between mortality data from [chronic kidney disease] and cardiovascular events. Thus, the efficacy of statins in treating other chronic diseases associated with inflammation is a very open question.”

The lead author of the current study, Dr. Ariela Orkaby, suggested to MNT that inflammation could be one of the mechanism underpinning the findings.

She said: “Statins lower inflammation. People with chronic kidney disease have higher rates of inflammation than the general population but also importantly, people with chronic kidney disease have a high risk of cardiovascular events. “

“So these are people who at baseline have a higher risk of cardiovascular disease. Part of our hypothesis was — if we we look and see whether they started statins or not, that [those who were taking statins] would also benefit just like other people who don’t have cardiovascular disease yet,” she added.

Insufficient evidence on the safety of statins in older individuals

Dr. Orkaby also said she and her colleagues had chosen to study this group of participants because there was a lack of information available on the impact of statins in older people.

A study published in 2022 by the U.S. Preventative Services Task Force showed that there was not sufficient evidence to determine the harms and benefits of statin use in people over 76.

Dr. Orkaby said:

“You know, the big class of people that we don’t have enough evidence in, is the growing aging population. So that’s people over 75. And there’s an ongoing trial right now called PREVENTABLE that is testing this. And that is really key because the largest group of people who are at the highest risk of cardiovascular events [are] older adults, and yet in the past they were routinely excluded from clinical trials.“

They were not the only group who had been underrepresented, and many could benefit from an analysis of how beneficial statins are in those groups, she added.

Dr. Orkaby emphasized: “Women historically have been underrepresented. If we look across autoimmune disorders, people with rheumatoid arthritis and similar conditions. These are people who have not been included in trials and yet there’s emerging evidence that statins may play a role for lowering the risk of future heart attacks.”

The researchers hope that future clinical trials will include more representative cohorts.

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