Very Low LDL May Mean More Cancer Risk

New research suggests a link between very low cholesterol levels and an increased risk of cancer, but the findings are far from conclusive, researchers say.

The analysis of studies examining outcomes in patients taking cholesterol-lowering drugs called statins to lower their low density lipoprotein (LDL) "bad" cholesterol found an elevated risk of cancer among those who achieved the very lowest LDL cholesterol levels while taking the drugs.

The findings do not directly implicate statins in increasing cancer risk, but they do raise important questions, which need to be answered in future clinical trials, researcher Richard H. Karas, M.D., of Boston's Tufts-New England Medical Center, tells WebMD.

Statins like Lipitor, Pravachol, Crestor, and Zocor lower LDL levels by blocking a key enzyme in the liver responsible for making cholesterol.

"Our findings should not be seen as a reason to change clinical practice," Karas says. "No one who needs these drugs should stop taking them based on these findings."

Millions of Americans take statins to lower their risk of heart attack and stroke, and in recent years an increasing number have been placed on high doses of the drugs to achieve lower LDL levels.

The "lower is better" strategy for controlling LDL has been shown to reduce cardiovascular risk, especially in very high-risk heart patients. But questions remain about the long-term safety of high-dose statin use.

Karas and colleagues did not have cancer in mind when they set out to examine the safety of the strategy. They were more focused on two more widely suspected side effects of statins — muscle damage and elevated liver enzymes.

They found no link between very low LDL levels and either of these side effects, but a clear association was seen between statin use in high doses and liver abnormalities.

"There was an important and significant relationship between the dose of statins given and the risk of liver toxicity," Karas says. "I think this paper establishes that point quite strongly."

The analysis failed to show a similar link between statin dosage and muscle damage. It has long been suggested that in high doses statins raise the risk of a rare but potentially life-threatening muscle disorder known as rhabdomyolysis.

No evidence of a link was found by Karas and colleagues, but the researcher says there were too few cases of the disorder to prove or disprove the association.

Karas favors using moderate doses of statins in combination with other cholesterol-lowering drugs instead of high doses of statins to lower the risk to the liver.

"To be clear, the benefits of statins far outweigh the risks," he says.

It is not clear from the analysis if the increased cancer risk seen in patients with very low LDL had anything to do with statin use.

The study is published in the July 31 issue of the Journal of the American College of Cardiology (ACC).

In an interview with WebMD, ACC President James Dove, M.D., FACC, expressed concern that it would be misinterpreted by the press and public.

"It would be wrong to conclude that the drugs are too risky because of this unproven cancer risk," he says. "These results raise important questions, but they do not demonstrate a causal relationship between statins and cancer."

Editors of the ACC journal expressed a similar apprehension in an editorial accompanying the research analysis.

"Given the growing public angst regarding the safety of prescription medications, all were concerned that the paper contained great potential both for harm and good," editors Anthony DeMaria, M.D., and Ori Ben-Yehuda, M.D., write.

The study prompted "spirited discussions" among editorial board members, with some arguing that the paper should not be published, the editors write.

"In the final analysis, the consensus was that these findings could not be ignored, that they did indeed warrant further investigation, and that they should be aired in public," they conclude.

Lipitor manufacturer Pfizer issued a statement late Monday in response to the study, noting that "the existing pre-clinical and clinical evidence does not support a causal association between the use of statins and the development of cancer."

A Pfizer spokeswoman pointed to a large analysis of 26 studies including nearly 90,000 patients published last year, which showed no evidence of an increased risk of cancer with statin use.

"A limitation of the current analysis is that researchers took data from clinical trials available before November of 2005," the statement reads. "We agree with the authors that further analysis in this area is appropriate, but should include all currently available trials."

By Salynn Boyles
Reviewed by Louise Chang, M.D.
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