Bird flu and statins

In an extremely interesting article in the Clinicians Biosecurity Network Weekly Bulletin (issue of 9/27/05) Borio and Bartlett review a suggestion of David Fedson, an expert on vaccines (and former Director of Medical Affairs at Aventis Pasteur), that statins (tradenames Zocor or Lipitor) might be helpful in preventing serious complications of influenza, perhaps by dampening the cytokine response.

The statins are widely used and available drugs used to lower cholesterol. They also have anti-inflammatory activities, perhaps by preventing activation of the transcription factor NF-kappaB. One mechanism thought to underlie the virulence of the H5N1 virus is production of a "cytokine storm," an unregulated systemic inflammatory response that results in a rapidly developing generalized clotting disorder, hemorrhage, kidney failure and fluid-filled lungs. The phenomenon is similar to or the same as what is called gram-negative sepsis or septic shock, a serious complication of bacterial infections that claims 400,000 to 500,000 lives each year in the US and has 50% to 70% mortality. Treatment for sepsis is a high priority independently of any role for the same or similar mechanism in influenza.

The idea that statins might be helpful for sepsis or influenza is based on more than speculation about mechanism. In 2004 Almog et al. (Circulation, Aug 17 2004;110(7):880-885) reported that patients admitted to the hospital with acute bacterial infections and who were on statins for more than a month for other reasons had a dramatically reduced incidence of severe sepsis (19% versus 2.2%) and reduced admission to the Intensive Care Unit (12.2% vs. 3.7%). An interesting point is that patients on statins might be expected to be at greater risk because they are taking a medication for a pre-existing medical condition.

Another study (.pdf available free on line here) looked back at the experience of over 700 patients that were admitted to a hospital for pneumonia. About 100 of them were also taking statins. Using 30-day mortality as a measure of outcome, the statin group had about two thirds fewer deaths than the non-statin group (odds ratio .36, 95% confidence interval .14 - .92).

Borio and Bartlett also report on an article from The Netherlands by Enserink to appear shortly in Science (hence not available to me other than through their summary). Enserink examined influenza seasons between 1996 to 2003, and using a database of 60,000 primary care patients compared those with at least two statin prescriptions in the previous year to those without. There was a 26% lower risk of pneumonia in the statin group. Because of the imprecision of the measure of statin use, I would expect the statin effect to be even greater than reported here.

Borio and Bartlett conclude:

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.

This is extremely interesting work. It is too early to say that prophylactic statin use in a pandemic is a reasonable strategy, but it is worth considering.