Researchers at Tianjin Medical University in China report that statins, which are commonly prescribed to lower blood cholesterol levels, may also offer significant benefits to patients admitted to the intensive care unit (ICU) with a sepsis diagnosis. These findings, published today in Frontiers in Immunology, were obtained in a retrospective study that looked at over 12,000 ICU patients at the Beth Israel Deaconess Medical Center in Boston.
“Our large, matched cohort study found that treatment with statins was associated with a 39% lower death rate for critically ill patients with sepsis, when measured over 28 days after hospital admission,” said Caifeng Li, PhD, associate professor at Tianjin Medical University General Hospital and first author of the study.
Sepsis is a life-threatening condition that occurs when the immune system generates an extreme inflammatory response to an infection, which can damage tissues and organs across the body and lead to organ dysfunction and failure. Despite early interventions to treat sepsis and prevent it from developing into septic shock, mortality rates remain high, with nearly 28% of patients hospitalized for sepsis in the U.S. dying every year.
Statins are widely used as a protective treatment to reduce the risk of cardiovascular disease properties. In recent years, there has been a growing interest in using statins to treat disorders where inflammation plays a key role, such as autoimmune diseases, multiple sclerosis and cancer.
“Statins have anti-inflammatory, immunomodulatory, antioxidative, and antithrombotic properties,” said Li. “They may help mitigate excessive inflammatory responses, restore endothelial function, and show potential antimicrobial activities.”
These properties have sparked an interest in studying the effect of statins on sepsis patients. However, previous studies have presented conflicting results, which Li and colleagues attribute to design limitations and the relatively small sample sizes reported in clinical studies to date.
“Previous randomized controlled trials may not have found a benefit of statins in patients with sepsis due to underreporting of sepsis diagnosis, small sample sizes, and failure to account for the complex interactions between statin use and patient characteristics,” Li added.
Randomized controlled trials are the gold standard to obtain clinical evidence, but they can be challenging to conduct due to high costs and intensive use of time and resources, especially in large patient cohorts. In order to study a larger patient population, the researchers opted to instead run a retrospective trial that relied on propensity score matching to adjust for any potential confounders.
The study was based on anonymized records from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database, which includes data from 265,000 patients admitted to the ICU of the Beth Israel Deaconess Medical Center. Adults with a sepsis diagnosis who were hospitalized for longer than 24h between 2008 and 2019 were selected and assigned a propensity score to determine how likely they were to be prescribed statins according to numerous variables such as age, gender, respiratory rate, disease history and multiple relevant lab values. Patients who received statins during their ICU stay were matched one by one to patients who had the most similar propensity score and were not treated with statins, resulting in two matched cohorts of 6,070 patients each.
An analysis of the data showed that the 28-day mortality rate was 14.3% for patients who received statins, compared to 23.4% for patients who did not receive statins, which is equivalent to a relative mortality reduction of 39% associated with statin treatment. These results were consistent when the patients were stratified into subgroups based on age, gender, race and body mass index (BMI). While the data showed that statin use was also linked to longer ICU stays and treatment, the researchers expect this to be a result of the lower mortality rate.
“These results strongly suggest that statins may provide a protective effect and improve clinical outcomes for patients with sepsis,” said Li.
The current study looked at statin use regardless of the type of statin. To better understand the effects of statins of sepsis patients, Li observed that future studies should look into more detailed patient data: “An ideal randomized controlled trial to confirm or reject our results should include a large sample size of sepsis patients, with detailed information on statin types, doses, and treatment duration. It should also carefully consider the timing of statin initiation and control for potential confounders.”
