Ask the Doctors: Fibrates may be better option than statins for some
A: Statins and fibrates act in fundamentally different ways. Statins, more officially known as HMG-CoA reductase inhibitors, target cholesterol in the bloodstream, most of which comes from the liver, not from foods that we eat. They work by binding to the enzyme HMG-CoA reductase, which the liver needs to form cholesterol.
Statins act in another way as well. Because they make cholesterol levels fall within the liver, the liver then increases production of a substance, or receptor, that takes LDL, the so-called "bad" cholesterol, from the bloodstream and shepherds it back into the liver. There, it is eventually removed via the bile. Because we make more cholesterol at night, statins are given before bedtime.
Fibrates, which include gemfibrozil (Lopid) and fenofibrate, target triglycerides in the bloodstream. They work by decreasing the liver's release of triglycerides and by increasing the production of lipoprotein lipase, which breaks down triglycerides. In addition, fibrates increase the formation of HDL, the so-called "good" cholesterol; they have only minor effects in reducing LDL. Unlike statins, fibrates should be taken before eating.
Statins have undeniably shown benefits in decreasing the risk of both heart attacks and strokes; fibrates seem to have a more narrow benefit. In 2010, a Lancet review analysis of 18 studies involving more than 45,000 patients showed a 13 percent decrease in heart attacks and angina among people who were taking fibrates, but no reduction in stroke risk, no decrease in overall death rates and no decrease in death rates from heart attacks.
A 1987 study published in the New England Journal of Medicine also showed mixed results. It followed more than 4,000 middle-aged men with elevated triglyceride levels for five years. At the start of the study, one group began using gemfibrozil, and the other group began taking a placebo. At the end of the study, the group that took gemfibrozil had a 34 percent decrease in the risk of coronary heart disease, but there was no difference in the death rate.
Overall, statins appear to have greater benefit than fibrates in decreasing the risk of both heart attacks and strokes. That's not to say fibrates aren't the right choice for some people, however. Significant elevation of triglycerides, greater than 400, can cause inflammation of the pancreas, so people with very elevated triglyceride levels would benefit from a fibrate medication. So too might those with elevated triglycerides and normal LDL cholesterols.
Before you suggest combining a statin and a fibrate for added benefit, be aware that the combination can increase the risk of muscle aches and possible muscle breakdown. On occasion, I will prescribe this combination to my patients with very elevated triglycerides, but I monitor them carefully for any signs of muscular problems or breakdown. Also in such cases, I try to lower the statin dose to decrease the chance of muscular symptoms.
In summary, statins and fibrates work by different mechanisms. Statins have greater benefit than fibrates in decreasing heart attacks and strokes. Fibrates, though, may be appropriate for people with elevated triglyceride levels.
Robert Ashley, M.D., is an internist and assistant professor of medicine at the University of California, Los Angeles.
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