FAQ: Preventing First-Time Heart Disease With Cholesterol-Lowering Drugs
Daniel J. DeNoon
WebMD Health News
Latest Cholesterol News
Reviewed By Laura J. Martin, MD
April 2, 2010 – Should healthy people take a cholesterol-lowering drug to prevent heart disease even if they don't have high cholesterol?
The answer, for some people, is yes. It's a controversial answer that raises a lot of questions. Here are WebMD's answers to those questions.
Who should consider taking statins to prevent heart disease?
In February 2010, the FDA approved the use of AstraZeneca's statin drug Crestor for preventing first-time heart disease. The approval is for people who meet all of the following conditions:
- Age: Men 50 or older or women 60 or older
- High blood levels of C-reactive protein (CRP, at or over 2 mg/L as measured on the hsCRP test)
- At least one other risk factor for heart disease, such as high blood pressure, low HDL "good" cholesterol, smoking, or a family history of premature heart disease
Not included on this list is a high level of LDL "bad" cholesterol. Why? LDL cholesterol is a major contributor to heart disease. But half of all heart attacks and strokes happen in apparently healthy people with LDL cholesterol levels below the current level of concern.
Can a statin drug help such patients? One controversial idea was to test a statin -- AstraZeneca's Crestor -- in people with normal cholesterol levels but high levels of CRP. CRP is a measure of inflammation in the body. Inflammation is a major part of the process leading to heart disease.
The AstraZeneca-sponsored JUPITER clinical trial enrolled 17,802 men over age 50 and women over age 60 with high CRP levels but with LDL cholesterol levels under 130 mg/dL (their average LDL level was 108 mg/dL).
An independent review panel stopped the trial after two years when it became apparent that patients receiving a placebo were having more heart attacks, strokes, angina (heart pain), and death from cardiovascular disease than those taking 20 milligrams of Crestor daily.
Even so, the risk wasn't extreme. There were 251 heart disease events in the 8,901 placebo patients and 142 events in those taking Crestor. But this 44% relative reduction is about twice as great as seen in most clinical trials of statins that enrolled patients with high LDL cholesterol.
So who should consider taking Crestor or perhaps another statin to prevent heart disease? The answer: men 50 years of age or older and women 60 years of age or older with relatively low cholesterol but with other factors that put them at high risk of heart disease should discuss statin therapy with their doctors, especially if they have high CRP levels.
The results of this discussion will vary. Different people have different constellations of heart disease risk -- and different reasons they should or should not take statin drugs.
Whether to start taking statin drugs is not a simple decision. Once a person starts statin therapy, treatment may continue for life. And while generic drugs cost less, treatment isn't cheap. Crestor, which is not available as a generic drug, costs about $3.45 per day.
Can any statin prevent heart disease in people with normal cholesterol levels?
Statin drugs currently on the market include Crestor, Lescol, Lipitor, Mevacor, Pravachol, and Zocor. The JUPITER trial isn't the first to show that statins can prevent heart events even in people with normal cholesterol levels.
However, Crestor is the only statin approved by the FDA for preventing first-time heart disease in people who do not have high cholesterol.
While it's tempting to conclude from available data that any statin might have the same effect at effective doses, this has not been proven in clinical trials. And not all statins are the same. Some have more potent effects at lower doses, and some are more likely than others to cause side effects.
Does CRP cause heart disease?
Few issues are more hotly debated by researchers than the role C-reactive protein (CRP) plays in heart disease.
Inflammation swells cholesterol-crammed artery walls, making the lining of those arteries vulnerable to breaking down or bursting. When the lining of an artery wall is disrupted, a cascade of events is set off, culminating in the formation of a blood clot, which can go on to cause a potentially deadly heart attack or stroke.
Some studies suggest CRP plays a major role in the development of heart disease. Others suggest it's merely a marker for the process that is the real culprit, while still others reject CRP as a distraction.
The consensus of opinion is that high CRP levels indicate high risk of heart disease.
In the JUPITER study, participants' CRP levels were very high -- at least 2 mg/L. But all by itself, CRP did not identify the patients whose risk of heart disease was lowered by statin therapy. All of the patients who benefited had at least one other traditional risk factor for heart disease: family history of premature heart disease, high blood pressure, smoking, or low HDL "good" cholesterol.
What are the risks of statins for healthy people who do not have high LDL cholesterol?
Neither Crestor nor other statins are without risk. This means that these risks should be weighed carefully against expected benefits.
Statins are linked to a number of minor side effects. They also are linked to a rare but serious side effect: muscle breakdown.
In its mildest form, this appears as myositis, a painful inflammation of the muscles. A muscle enzyme called CPK may build up in the blood. The most serious form of muscle breakdown is rhabdomyolysis, in which muscles all over the body become painful and weak. A flood of muscle proteins collects in the kidneys and can lead to kidney failure and death.
Another troubling problem linked to statin use is an increased risk of diabetes. This risk became apparent in the JUPITER trial, in which more individuals taking Crestor developed diabetes than those taking placebo.
A 2010 analysis of statin clinical trials suggests that increased diabetes risk is linked to all statins, not just Crestor. It appears to occur more often in patients over age 60.
How big is the risk? The study found that if 255 patients take a statin for four years, the drugs will cause one extra case of diabetes. Meanwhile, the drugs would prevent 5.4 heart-related deaths or heart attacks. Overall, the benefit of statins in reducing heart disease risk is nine times greater than the drugs' danger of increasing diabetes risk.
However, this finding suggests that older patients taking statins should have their blood sugar levels checked regularly.
SOURCES: FDA, Crestor primary prevention approval letter, Feb. 8, 2010.
FDA, Crestor label, accessed April 2, 2010.
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