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Could Statins Improve the Outcome of Influenza?

By Luciana Borio, M.D. and John G. Bartlett, M.D., September 29, 2005

Dr. David Fedson, former Director of Medical Affairs at Aventis Pasteur MSD, recently suggested that statin therapy might have a role in ameliorating the natural course of severe influenza infection, and its use in this setting should be investigated further (Bulls, Bears, and Birds: Preparing the Financial Industry for a Pandemic, NY, 9-23-05).

Statin (HMG-CoA reductase inhibitor) therapy in cardiovascular disease stems from its lipid-lowering effect as well as its anti-inflammatory properties. Statins have been shown to prevent the activation of NF-kappaB, a transcription factor involved in the activation of cytokine genes during inflammation. Influenza virus also triggers the release of cytokines.

In a prospective, observational cohort study of 361 patients, prior statin therapy for at least one month before the onset of acute bacterial infection was associated with a decreased rate of both severe sepsis and ICU admission [1]. Severe sepsis developed in 19% of patients off statin therapy and in 2.4% of patients on statin therapy (RR 0.13, 0.03-0.52). Furthermore, 12.2% of patients off statin therapy required ICU admission, compared with only 3.7% of patients on statin therapy (RR 0.30, 0.1-0.95). This was especially significant since patients treated with statins have significant comorbidities, which impart a worse prognosis after serious infections.

A more recent retrospective cohort study examined the effect of prior use of statins on 30-day mortality for patients hospitalized with community-acquired pneumonia [2]. Of 787 patients, 110 (14%) were on statins at presentation. In a multivariable regression analysis, the use of statins was associated with decreased 30-day mortality (odds ratio of 0.36, 95% confidence interval 0.14-0.92).

In an article in this month’s edition of Science [3], Ensirink reports on an epidemiological study from the Netherlands, in which the researchers examined a database of 60,000 primary care patients. They found that during influenza seasons between 1996 and 2003, patients who had at least two statin prescriptions in the previous year had a 26% lower risk of developing pneumonia. (This data is not yet published but was presented at The Second European Influenza Conference in Malta, 9-11-2005.)

These studies suggest that statin therapy may ameliorate the course and/or prevent complications of influenza.
In these studies, it appears that all of the people were already receiving statins when they got infected. Whether statins would be beneficial after the onset of symptoms is still unknown. However, further investigation is merited. This is particularly important given the likelihood that vaccines and antiviral agents will be in short supply during an influenza pandemic, and statins are widely available and may be produced relatively inexpensively.

References

  1. Almog Y, Shefer A, Novack V, et al. Prior statin therapy is associated with a decreased rate of severe sepsis. Circulation. Aug 17 2004;110(7):880-885.

  2. Mortensen EM, Restrepo MI, Anzueto A, Pugh J. The effect of prior statin use on 30-day mortality for patients hospitalized with community-acquired pneumonia. Respir Res. Jul 25 2005;6:82.

  3. Enserink M. Infectious disease. Old drugs losing effectiveness against flu; could statins fill gap? Science. Sep 23 2005;309(5743):1976-1977.