Could statins reduce death risk in chronic kidney disease

Statins, known for their efficacy in reducing low-density lipoprotein (LDL) cholesterol or ‘bad’ cholesterol, are increasingly being recognized for their broader health benefits. Originally prescribed to heart attack patients to prevent recurrence, statin use is now being constantly updated to include more groups who could benefit from the drug. A recent trial has indicated that older adults with chronic kidney disease could also benefit from statin use.
In 2020, statins were the most prescribed drug in the United States. They work by lowering levels of LDL cholesterol, preventing the hardening and narrowing of arteries, which can lead to high blood pressure. Unlike earlier interventions that focused on lifestyle changes like diet and exercise, statins have proven more effective in reducing LDL cholesterol.
The maximum safe dose of some statins can reduce LDL cholesterol levels by up to 55%, a significant achievement recognized by the 1985 Nobel Prize in Physiology or Medicine. A 2002 study in The Lancet showed a 25% reduction in heart attack and stroke risk over five years in high-risk cardiovascular disease patients taking 40 mg of simvastatin daily.
The REPRIEVE trial, recently reported in The Lancet, found that the statin pitavastatin lowers the risk of cardiovascular events by 35% in people with HIV. This has led to calls for guidelines to recommend statin use for all people with HIV over the age of 40.
A study published in JAMA Network Open has now shown that older adults, predominantly men, with chronic kidney disease could benefit from taking statins. The study analyzed data from 17,609 U.S. veterans over the age of 65 with moderate chronic kidney disease. It found that taking statins reduced overall mortality in these veterans by 9%, although the reduction in major adverse cardiovascular events was not significant.
The study did not speculate on the mechanism behind these findings but called for further randomized control trials. Dr. Barry Sears, a researcher not involved in the study, hypothesized that statins might activate the AMPK pathway, a major controller of inflammation, thereby reducing mortality in chronic diseases like kidney disease.
Dr. Ariela Orkaby, the lead author of the study, suggested inflammation reduction as a potential mechanism. Chronic kidney disease patients have higher rates of inflammation and a high risk of cardiovascular events, and statins’ ability to lower inflammation could be beneficial.
There is, however, insufficient evidence on the safety of statins in older individuals. A 2022 study by the U.S. Preventative Services Task Force indicated a lack of sufficient data to determine the harms and benefits of statin use in people over 76. Dr. Orkaby highlighted the lack of evidence in older populations, women, and people with autoimmune disorders, emphasizing the need for more inclusive clinical trials.
The ongoing PREVENTABLE trial is expected to provide key insights, especially as the aging population, at high risk of cardiovascular events, has historically been excluded from clinical trials.
—Hannah Flynn