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Lower Cholesterol to Lower Heart Risk

by Wayne L. Clark

There are consistent, though uncommon, reports of muscle weakness and aches in people taking statins, though the incidence has been the same in clinical trial participants taking placebos. One in every thousand people taking a statin develops a condition called myositis, with an elevated level of the muscle enzyme creatine kinase (CPK) accompanying the muscle aches. Rarer still, about one in every 10,000 people taking a statin progresses to serious muscle disease and acute kidney failure, although the early signal from raised CPK levels should give plenty of time to stop therapy before that happens.

The benefits of statins nonetheless far outweigh the rare serious side effects, according to a clinical advisory from the American College of Cardiology, the American Heart Association, and the National Heart, Lung, and Blood Institute.

“Given a one-in-five chance of heart disease in diabetes,” Dr. Keilson says, “the one-in-10,000 chance of serious side effects from the statins shouldn’t keep anyone from reaping the benefits of the therapy.”

A five-year study funded by the National Institutes of Health comparing the side effects of simvastatin and pravastatin against placebo is due to be completed this year. The $5 million study is investigating issues such as muscle pains and anecdotal reports of cognitive dysfunction in people taking statins.

Alternative LDL-lowering drugs include the bile acid sequestrants, such as cholestyramine (Questran, Questran Light) and colestipol (Colestid). These drugs lower LDL cholesterol and have few serious side effects, though they have been associated with bothersome gastrointestinal side effects. Some may also find cholestyramine and some forms of colestipol unpalatable because they are powders or granules that must be mixed with water. (A tablet form of colestipol is available.) A newer drug in this class, colesevelam (WelChol), comes in tablet form and may be better tolerated and as effective as its predecessors.

The bile acid sequestrants can raise triglyceride levels, so in a person with high triglycerides, nicotinic acid, or niacin, is sometimes used instead because it has been shown to decrease levels of LDL cholesterol and triglycerides and to raise levels of HDL cholesterol. The Coronary Drug Project examined the benefits of niacin in people who had had heart attacks and found an 11% lower mortality after 15 years. The side effects of therapeutic niacin treatment include flushing, gastrointestinal upset, and liver damage. Flushing can be reduced by using extended-release (Niaspan) or sustained-release formulations of niacin, but risks of liver damage increase with use of sustained-release (but not extended-release) niacin.

Niacin can also cause high blood glucose levels in some people, so there has been concern about using it in people with diabetes. However, a study published in 2000 concluded that niacin could be safely used in people with diabetes, increasing HDL levels by 29% while lowering LDL levels by 8% and triglycerides by 23%. Current guidelines for people with diabetes allow for its use with mindfulness of the potential side effects.

Ezetimibe (Zetia) is the first in a new class of drugs called cholesterol absorption inhibitors. In clinical trials, it has significantly lowered LDL levels and moderately lowered triglyceride levels and raised HDL levels. Ezetimibe is much better tolerated than the bile acid sequestrants and may ultimately replace them in routine therapy.

Lowering triglycerides
Once LDL levels are brought under control, the next step is to address elevated triglyceride levels. The drugs of choice for this therapy are the fibrates: gemfibrozil (Lopid), clofibrate, and fenofibrate (Lofibra, Tricor). In addition to lowering triglycerides, they also moderately lower LDL cholesterol and can change the size of LDL particles from the small, dense type that is more likely to cause atherosclerosis to a larger type. The most common side effects of the fibrates are primarily gastrointestinal symptoms.

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