High-Dose Statins Reduce Mortality in Sepsis Patients

February 4, 2009 (Nashville, Tennessee) — Current use of moderate to high doses of statins for patients hospitalized with sepsis was associated with a mortality risk reduction of more than 20%, compared with patients not taking statins, investigators reported here at the Society of Critical Care Medicine 38th Critical Care Congress.
Results of a retrospective review of 25,587 patients 50 years and older who were hospitalized with sepsis between 1999 and 2004 were presented by Ahmed I. Shah, MD, from the Department of Cardiology at Kaiser Permanente Los Angeles Medical Center, in California. The group was approximately half men and half women, and the mean age was 72 years.
Dr. Shah's team divided patients into 3 groups, according to statin use: current users, who were taking a statin before and on the day of hospitalization; remote users, who had taken a statin 2 or more months before hospitalization, but not afterward; and never users, who had not taken a statin for at least 1 year before admission.
Current users were divided into a low-dose group and a high-dose group. Low dose was defined as lovastatin 40 mg or less daily, simvastatin 10 mg or less daily, and atorvastatin 10 mg or less daily.
Of the cohort, 70% were never users, 11% were remote users, and 19% were current users. Of the current users, approximately half were on low doses and half were on moderate to high doses. Current users were more severely ill and had more comorbidities than never users.
Patients were followed for up to 12 months after admission or until death. Twelve-month mortality rates were calculated.
The adjusted hazard ratios for all-cause mortality were:
0.83 (0.76–0.91; P < .0001) for current users vs never users;
0.76 (0.72–0.81; P < .0001) for current users vs remote users;
0.87 (0.79–0.96; P < .009) for low-dose users vs never users;
0.79 (0.72–0.88; P < .0001) for high-dose users vs never users; and
0.90 (0.83–0.99; P < .03) for high-dose vs low-dose users.
"In hospitalized septic patients, current high-dose statin use is associated with a statistically significantly lower rate of 1-year mortality," Dr. Shah told meeting attendees. However, he emphasized that this was a retrospective review and not a prospective interventional study.
"This has become a very hot area for research over the past 5 to 6 years, but most of the data are like this," Robert Duncan Hite, MD, FCCP, associate professor of medicine and director of the Medical Intensive Care and Critical Care Research Section on Pulmonary, Critical Care, Allergy and Immunologic Disease at Wake Forest University School of Medicine, in Winston-Salem, North Carolina, told Medscape Critical Care in an interview after Dr. Shah's presentation.
These are "retrospective analyses of large databases in which the use of statins is examined but cannot be controlled for other important variables that might explain differences in outcomes," Dr. Hite said.
"There are several prospective, randomized, blinded trials currently ongoing around the world. Even once those [results] are available, and assuming they prove to be successful, we will still not know whether all statins [are] of equal benefit and what the optimal dose is," he pointed out. "Since statins are not without toxicity and little is known about the metabolism of statins in sepsis, dosing will have to be considered carefully."
Dr. Hite concluded: "For now, I would not recommend that statins be initiated in a septic patient, but it is reasonable to continue statins in a septic patient previously taking a statin. This is a change that I and many others have made in their practice over the past few years as a result of data similar to the data provided by this study.
Drs. Shah and Hite have disclosed no relevant financial relationships.