Tuesday, July 21, 2009

4. Do Statins Protect against Sepsis?

Quite surprisingly, you can easily find web pages that hail the benefits of statins beyond their ability to lower cholesterol (already a dubious achievement). The claims they make directly contradict the actual effects of statins. For example, if you do a web search on "statins cancer", you will find several hits claiming that statins may be protective against cancer. Several recent articles on the Web have suggested that statins may protect against sepsis. I am almost certain that both of these claims are false.

We'll start with sepsis, and with an article that illustrates how sloppy science gets turned into truth when it migrates into the media. (Statins Reduce Sepsis Risk) . I quote here the lead sentence of the story:

"Cholesterol-lowering drugs can reduce the risk of severe infection in patients suffering from heart disease or stroke, scientists said on Wednesday."

This sounds like a fact, but instead it is the result of a flawed study, as I will argue below. The conclusion was drawn on the basis of a retrospective study of patients who had had a heart attack or stroke. "Retrospective" means to take a look back at something that has already taken place. Some of the patients had been prescribed statins and some had not, a decision surely based on their cholesterol profile. Thus, those who were not prescribed statins must have had naturally occurring low cholesterol, even though they suffered from a disease commonly treated with statins. Although high cholesterol is correlated with heart disease incidence, it is by no means the case that if you have heart disease you must have high cholesterol.

Another very strong risk factor for heart disease and stroke is diabetes, (in fact, it is sometimes referred to as a cardiovascular disease) (Diabetes and Heart Disease) . (Diabetes and Stroke) . Diabetes is also a risk factor for sepsis (Diabetes and Sepsis) , because untreated diabetes often leads to sores in the extremities that won't heal, which can lead to subsequent gangrene and amputations. It is quite plausible that those in the retrospective study who did not have high cholesterol were more likely to have diabetes (the causative agent of their heart attack or stroke), a condition which causes increased risk to sepsis.

The above claim that cholesterol-lowering drugs can reduce the risk of severe infection in patients suffering from heart disease or stroke is directly contradicted in the conclusion of an excellent article that carefully examined several studies on sepsis. These authors concluded that statin therapy should be temporarily halted during a sepsis event [27]. (Statins Following Sepsis Event) .

"Statins are effective at lowering lipid levels, but lipids are the wrong target in sepsis. Higher lipid levels are desirable in these patients."

He goes on to say: "Research has shown that hypocholesterolemia [low cholesterol] in critical illness and multisystem organ failure correlates with decreased patient survival rates." This can be translated into "if your cholesterol is low, you have a worse chance of surviving."

A careful study of all the available evidence that statins may protect against sepsis, titled simply, "Statins and Sepsis," [7] was published by Professor Fang Gao at the University of Warwick in the U.K. in the British Journal of Anesthesia in 2008. (Statins and Sepsis: Review Study) . At the end of the study, he wrote this caveat: "However, there have been no RCT [randomized controlled clinical trials] of statins in sepsis, and large randomized controlled clinical trials with clinically relevant primary endpoints are desperately needed." In the paper, he mentioned the ASEPSIS trial, that was underway at the time, and which he claimed would be completed by 2008. A "Declaration of interest" at the bottom of the paper said the following:

"Professor Gao is the Chief Investigator of RCT on Statin therapy in the ASEPSIS trial. The trial received a pump-prime research grant from Pfizer. Professor Gao and Dr Thickett have received travelling sponsorships from pharmaceutical and industrial companies to attend national and international conferences."

I.e., Professor Gao receives funding and perks from Big Pharma that surely influence his research bias.

Since it is now June, 2009, I was eager to find the results of the ASEPSIS trial on the Web. I did find a pointer to the trial itself, (ASEPSIS Trial) , and a very encouraging title: "Randomised double-blind placebo-controlled trial of 40 mg/day of Atorvastatin on reduction in severity of SEPSIS in ward patients." The trial web site indicated that indeed the trial had been completed in January, 2008, i.e., eighteen months ago. But there was nothing there to indicate what the outcome was. The web search turned up no other pointer to this trial -- no papers, no media coverage. You can be sure that if this trial had had an outcome favorable to statins, it would have been all over the media. Thus, it is highly likely that this randomized double-blind placebo-controlled trial showed the exact opposite of the effect that was so eagerly anticipated. Once you remove the cholesterol bias, the effect goes away.


Anonymous said...

some people use Generic Viagra to protect against this condition, beside I was checking some pictures of this disease, what a horrible end have the person who suffers this.

Blogger said...

Informative content. I would like to say thank you for sharing this article. Know about the best diagnostic service centre in Kerala.