Statins Associated With Lower Risk for Death Among Hospitalized Influenza Patients

Daniel M. Keller, PhD

November 05, 2009

November 5, 2009 (Philadelphia, Pennsylvania) — Patients who were hospitalized for seasonal influenza while taking statin drugs experienced a 54% lower risk for death, in hospital or within 30 days of discharge, than patients who had not been using statins.

There is a growing body of evidence suggesting that statins have anti-inflammatory and immunomodulatory properties, and that influenza morbidity correlates with an inflammatory response. Statins have been seen to reduce pneumonia and influenza deaths. On the basis of these observations, researchers performed a retrospective chart review to investigate the effect of statin use on mortality among hospitalized patients with laboratory-confirmed seasonal influenza.

The Emerging Infections Program (EIP) Hospitalized Influenza Surveillance System covers 59 counties in 10 states, and includes 7% of the United States population. During the 2007/08 year, 2800 patients met the study inclusion criteria: being 18 years or older, residing in the EIP surveillance area, and being hospitalized with a positive influenza test. Patients with unknown statin use and those who were on mechanical ventilation, which would preclude oral statin therapy, were excluded.

Most patients were 65 years or older (n = 1596; 57%), 44% were male, 29% (801 of 2800) were using statins, and 3% (81 patients) died. Patients 65 years and older were about 3 times more likely to be receiving statins than younger patients. A higher proportion of whites (31.9%) and Asians (33.3%) were receiving statins than blacks (19.6%) or other ethnicities.

Using a multivariable logistic regression modeling strategy, researchers, led by epidemiologist Meredith VanderMeer, MPH, from the Oregon Public Health Division EIP in Portland, found that statin use during hospitalization was associated with a 54% lower risk for death during the observed period (odds ratio [OR], 0.46; 95% confidence interval [CI], 0.26 - 0.81). Whites were at a greater risk for death than blacks (OR, 3.98; 95% CI, 1.22 - 12.91).

Interestingly, using a bivariate analysis, Ms. VanderMeer told attendees here at the Infectious Diseases Society of America (IDSA) 47th Annual Meeting that "people who were vaccinated against influenza were actually more likely to die." She speculated that people with underlying health conditions might have been more likely to have been vaccinated. In the bivariate model, vaccination was associated with a 2.26-fold increased risk for death (95% CI, 1.30 - 3.95). Cardiovascular disease was a significant risk factor for death in this model (OR, 2.57; 95% CI, 1.61 - 4.08), but not in the multivariable analysis.

Ms. VanderMeer said that her study confirms and adds to the findings of one by Frost and colleagues (Chest. 2007;131:1006-1012), which found a lower risk for death from influenza among users of moderate statin doses. However, the current study had less chance of misclassification of disease (influenza was confirmed by a laboratory) and had a more accurate classification of patients using statins (medication administration records from charts were used, as opposed to drug prescriptions).

Some limitations of the study were that it was observational, with possible unmeasured confounders and misclassification of deaths. Also, "we weren't able to effectively look at the relationship between influenza vaccination status and statin use and death," Ms. VanderMeer said. "This was mostly because there was a poor vaccine match in the 2007/08 influenza season . . .  and around 60% of our cases were over the age of 65 and were less likely to have had a good immune response to the vaccine."

She concluded that statins are a promising area for further exploration and might be a useful adjunct to antiviral medications and vaccines. "However, our results do not say that people should be put on statins if they are hospitalized for influenza. There is definitely a need for randomized controlled trials to look at this further."

Ms. VanderMeer told Medscape Infectious Diseases that she has data on which statins patients were taking, but has not analyzed them yet to try to discern if any particular ones are more protective than others against death from influenza. A stumbling block to that analysis might be the low number of deaths recorded as part of the study and the variety of statins used.

The results of the study were based on patients with seasonal influenza 2 years ago. "It's hard to say whether or not those results would extrapolate to the pandemic situation," Ms. VanderMeer cautioned, "although the mechanisms should be similar. . . .  We definitely need those randomized controlled trials before we say for sure to go ahead and use statins."

Session moderator Andrew Pavia, MD, professor and chief of pediatric infectious diseases at the University of Utah Health Sciences Center in Salt Lake City and chair of the Pandemic Influenza Task Force of the IDSA, told Medscape Infectious Diseases that the study "is very provocative, and 'provocative' is the best word. It's an observational study, but it's a very well-done one." He said it controlled for many of the problems that can affect observational studies and provides a good basis for doing intervention trials testing statins to prevent death from influenza.

Dr. Pavia said more work also needs to be done to determine the pathogenic mechanisms in influenza and which parts of the immune system should be targeted by therapies. "Although we think that a dysregulated immune system plays a role in certain kinds of very severe influenza and that this is an attractive target, to date we don't have any interventions that have worked," he noted, "which is one of the reasons that this study is so provocative, because we don't have other good, very promising strategies for immune modulation that are far along.

"Steroids clearly have a broad pleiotropic effect on the immune response, and it's not surprising that [steroids] may do more harm than good because of that," Dr. Pavia said.

According to www.clinicaltrials.gov, a placebo-controlled trial sponsored by Vanderbilt University is recruiting patients to investigate the effect of rosuvastatin (Crestor, AstraZeneca) on hospitalized patients with H1N1 influenza. Another study is planned to look at the effect of simvastatin (Zocor, Merck and others) on cytokine expression in pneumonia. Canopus BioPharma is initiating trials of its novel aerosol formulations of widely used statins as a treatment for influenza.

The study did not receive any outside funding. Ms. VanderMeer has disclosed no relevant financial relationships. Dr. Pavia reports receiving consulting fees from NexBio and that he is taking a statin.

Infectious Diseases Society of America (IDSA) 47th Annual Meeting: Abstract 706. Presented October 30, 2009.

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