Can Statins Play a Role in Sepsis-Related Mortality?

PHILADELPHIA—Statins may lower mortality risk in patients with sepsis, said Ahmed Ijaz Shah, MD, at the American College of Chest Physicians 2008 Annual International Assembly.

Research shows that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors may be helpful in sepsis due to their pleiotropic anti-inflammatory and immunomodulatory effects, and possibly due to actions on endothelial dysfunction, noted Dr. Shah of the Department of Cardiology, Kaiser Permanente Los Angeles Medical Center; he cited one study that showed lower risk of sepsis related to statin use in patients with atherosclerosis. To confirm this connection with sepsis mortality, Dr. Shah and colleagues retrospectively reviewed statin use, demographics, and mortality in sepsis patients included in the Kaiser Permanente health care system database.

STATIN USE AND COMORBIDITIES

Using the International Classification of Diseases, Ninth Revision codes for sepsis and severity described in a 2003 epidemiology study, the researchers identified more than 23,000 patients 50 or older (mean age, 72) in the system for at least one year who were hospitalized with sepsis or severe sepsis between 1999 and 2004. The Charlson index was used to calculate a risk score for comorbidities.

With the help of pharmacy records, the researchers grouped patients based on their use of commonly prescribed statins: simvastatin, lovastatin, and atorvastatin. Current users had taken statins for at least two consecutive months prior to hospitalization, remote users had taken statins up to two months prior to hospitalization but none thereafter, and nonusers had not taken statins within the year prior to hospitalization.

Seventy percent of patients were nonusers; 11% were remote users, and 19% were current users. Charlson index scores and incidence of comorbidities (including diabetes, atherosclerosis, heart, lung, and kidney diseases, lipid disorders, hypertension, and heart failure) were higher among statin users than in nonusers; neoplasms, chronic central nervous system disorders (eg, Alzheimer’s and Parkinson’s diseases), and acute and chronic gastrointestinal and liver diseases were more common in nonusers.

STATINS REDUCE HIGH MORTALITY RATES

Sepsis was most often of respiratory and genitourinary or renal origin; gastrointestinal or hematologic causes, including bacteremia, were less common. The mortality rate was 52% one year after treatment. Of those who had undergone mechanical ventilation, there was a 37% higher risk of death. Patients with higher Charlson index scores had higher mortality.

When mortality rates were analyzed by statin use, significant differences in risk were seen (see Table). Although statin users were the sicker patients, current statin use was associated with a significantly lower one-year mortality rate, compared with remote use and nonuse, Dr. Shah stated. After adjustment for comorbidities, even remote use emerged as being beneficial, as it was associated with significantly lower mortality versus nonuse.

This was a hypothesis-generating study, Dr. Shah noted, and prospective controlled studies of statins and sepsis outcomes are warranted. “Given the high mortality associated with sepsis, I believe any intervention we can do will reduce severity and possibly have tremendous implications on sepsis care,” he concluded.

—Beth Tansey Peller, RN

Suggested Reading
Gupta R, Plantinga LC, Fink NE, et al. Statin use and sepsis events [corrected] in patients with chronic kidney disease. JAMA. 2007;297(13):1455-1464.
Hackam DG, Mamdani M, Li P, Redelmeier DA. Statins and sepsis in patients with cardiovascular disease: a population-based cohort analysis. Lancet. 2006;367(9508):413-418.
Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med. 2003;348(16):1546-1554.

Return to table of contents