A Downside of Statins?
Cholesterol-busting statins, which benefit an estimated 13 million Americans and 25 million people worldwide, protect against the ravages of heart disease caused by clogged coronary arteries. But they caused some palpitations last week, when the Journal of the American College of Cardiology released a report from Tufts University School of Medicine that the lower levels of cholesterol achieved by statin therapy are associated with an increased risk of cancer (1 extra cancer per 1,000 patients). The "C" word carries such a chill that the journal's own editors toyed with rejecting the report, fearing it would cause patients to dump their lifesaving pills. The better editorial angels prevailed, and the report is out, cushioned by cautionary commentary that the findings could be a statistical fluke. With medical practice shifting toward more intensive cholesterol-lowering treatment, based on numerous clinical studies that show a reduction in heart attacks and cardiovascular mortality, people are taking statins in droves--at higher doses and for life. So it is that much more important to sort out unexpected longer-term side effects.
Past research is actually mixed on a cancer-statin link. On the one hand, statins can cause cancers in rodents in doses comparable to those used in patients. And two large randomized clinical trials found a significant cancer increase--breast cancer in one, and a variety of cancers in the second, which studied only elderly patients. On the other hand, the vast majority of statin trials have found the opposite: The drugs have either had no effect or reduced cancer risk.
Unlike most treatment studies that look for drug benefits, the Tufts study set out to evaluate adverse effects of reducing LDL cholesterol with daily statins given at a low (10 to 20 mg), intermediate (40 mg), and the increasingly common high dose (80 mg), as gleaned from 16 randomized controlled statin trials. The patients were on a variety of statins--lovastatin, simvastatin, pravastatin, fluvastatin, and atorvastatin--and were followed for approximately one to six years. Predictably, as doses rose, there was an increase in statin-related muscle injury and liver inflammation.
What was not expected, however, was that in the 41,173 patients who were enrolled in the 10 trials that reported cancer rates, patients with the lower levels of LDL cholesterol and taking higher doses of statins were more likely to have had newly diagnosed cancer. The cancers were of many types, including breast, prostate, lung, and colon.
Prudence. It's quite possible that this connection is just a coincidence. Association does not mean causation. But one can't ignore the finding, either, particularly in the face of an exuberance about lowering cholesterol to levels that some people believe will put more than half the population over age 40 on statins. So before statins are put into drinking water, or other means devised to take cholesterol to superlow levels, cardiologists need to re-evaluate the mantra "lower is better."
The evaluation will take a while, since cancer has a long latency period requiring monitoring for more than 10 years. As a start, longer-term follow-up and analysis of malignancies in all patients enrolled in these existing trials of statins--and other therapies that reduce cholesterol--will help determine if the current findings are for real. There is also a need for further study of consumers of statins who are at greater risk for cancer, such as the elderly or cancer survivors, groups that are all too often excluded from randomized clinical trials.
In the meantime, it's only prudent to reinforce the importance of healthy habits and a low-fat diet along with drugs in order to ward off cardiovascular disease in those whose cholesterol levels are elevated. And statins in low to moderate doses are the most established and commonly used agents we have to help bring down an elevated LDL cholesterol to the standard goals of less than 130 mg/dL. But the more aggressive goals for LDL now sanction cutting that threshold number almost in half for many patients. If that means pushing statins beyond a moderate dose, then doctors and patients should have a serious discussion. For someone who has had a major heart attack, the upside is great enough to dwarf possible side effects. For others, any incremental cardiovascular benefit may not be worth taking a chance. They might decide that, for now, less is more.
This story appears in the August 6, 2007 print edition of U.S. News & World Report.