Oncology News Updates

Statins Don't Cause Cancer in Patients With Low LDL Cholesterol

Elsevuier Global Medical News
Aug 20, 2008

There is no evidence that statin use causes cancer, although patients who reduce their LDL cholesterol level with statins appear to have a significantly increased risk of the disease, Dr. Alawi Alsheikh-Ali and colleagues reported in the Sept. 30 issue of the Journal of the American College of Cardiology.

Because the association also occurs in untreated patients with low LDL cholesterol, it's probably driven by an as-yet-undefined relationship between cancer and low LDL cholesterol levels regardless of how they occur, the researchers wrote (J. Am. Coll. Cardiol. 2008 Sept. 30 [doi:10.1016/j.jacc.2008.06.037]).

Dr. Alawi A. Alsheikh-Ali of Tufts University, Boston, and colleagues previously observed a significant relationship between low LDL cholesterol levels and cancer among patients who take statins (J. Am. Coll. Cardiol. 2007;50:409-18). However, the meta-analysis upon which the conclusion was based examined the risk in treated patients only. Their new meta-analysis included data from both the active and control groups in 15 randomized, controlled trials of statin therapy, which comprised more than 97,000 patients and 437,000 person-years of follow-up.

During these trials, 5,752 patients developed a new cancer. The incidence was 4%-27% per 1,000 person-years in the statin arms, and 6%-24% per 1,000 person-years in the control arms.

The researchers cut the data in several ways: univariate and multivariate regression analyses; and Poisson fixed effects and Bayesian random effects analyses. The association between low LDL cholesterol levels and cancer among the statin-taking groups remained strong and statistically significant in almost every model.

However, the models also showed similar associations between cancer and low LDL cholesterol in the control arms, the researchers found. "This supports the notion that lowering LDL-C with statins does not contribute etiologically to cancer," they wrote. Therefore, they reasoned, something else must be driving the association. Although it could be a chance finding, the authors thought it more likely that the association might be influenced by "an unknown confounder that itself is related to cancer risk."

In an accompanying editorial, Dr. Daniel Steinberg of the University of California, San Diego, said the association represents "unsuspected sickness phenomenon": Rather than low LDL cholesterol causing cancer to develop, undiagnosed early cancers were probably causing some patients to develop low LDL cholesterol levels (J. Am. Coll. Cardiol. 2008 Sept. 30 [doi:10.1016/j.jacc.2008.06.036]).

"We know that cancers can significantly lower cholesterol levels as much as 10 years before they surface clinically," Dr. Steinberg wrote. "The randomly recruited cohorts in the large statin trials undoubtedly included some subjects who had low LDL [cholesterol] levels at the time they entered the study because they already had cancer."

Tumor cells have large numbers of LDL cholesterol receptors and use LDL cholesterol at a higher rate than do normal cells, Dr. Steinberg said. Because of this increased catabolism, any large randomly recruited population that is followed for at least 5 years, with no statin treatment at all, will show more cancer deaths in those with the lowest baseline LDL cholesterol levels.

"The central question for the clinician is whether a low LDL carries with it any intrinsic danger of cancer or other serious consequences," he said. "Almost certainly not." Cells take up as much LDL cholesterol as they need, even when levels are extremely low, so there should be no hesitation in aiming for LDL cholesterol levels of 50-70 mg/dL in high-risk patients, he concluded.

Two of the study researchers disclosed ties to Pfizer Inc. One of the researchers disclosed ties to Merck and Co., Abbott Laboratories, and AstraZeneca Pharmaceuticals LP. All four companies manufacture statins.

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