Everyone's got enemies. But our fiercest foe is heart disease. It's the No. 1 killer of Americans, and while it affects both sexes, it tends to nab men at an earlier age than it does women. Just last month, however, the Food and Drug Administration made a move that many cardiologists call a boon for prevention: The agency OK'd the use of a cholesterol-lowering drug, a statin called Crestor, in folks whose cholesterol levels are normal and whose doctors haven't diagnosed them with heart disease. The move aims to better shield millions more Americans against future heart attacks, strokes, heart procedures, and surgery.
The FDA's decision hinged on the results of a large study, called the Jupiter trial, published in the New England Journal of Medicine in 2008. Jupiter took almost 18,000 middle-aged adults and assigned them to either Crestor or a sugar pill. Under national guidelines, the study participants would not have normally been prescribed a statin because their levels of "bad" LDL cholesterol weren't high enough (all had LDL's below 130 mg/dL), explains Paul Ridker, a cardiologist at the Brigham and Women's Hospital in Boston and lead author of the study, which was funded by AstraZeneca, the drug's maker. But all of the participants had elevated levels of high-sensitivity C-reactive protein (hs-CRP), a measure of inflammation. While inflammation is the body's natural response to infection and injury, it also foments artery-clogging plaque and seems to make that plaque more likely to rupture and cause blood clots that trigger heart attacks and strokes, experts say. Researchers hoped Crestor might lower the risk of cardiovascular problems since statins also reduce CRP.
After two years, the trial was halted early because volunteers on Crestor were so much less likely to have heart attacks, strokes, and procedures such as coronary artery bypass grafts than those taking a placebo. The trial, says Steven Nissen, chairman of the department of cardiovascular medicine at the Cleveland Clinic, was a "blockbuster" and suggests an "important change in thinking about who ought to be treated" with statins. (The FDA apparently agrees.) Jupiter has also suggested a change to the usual heart disease prevention strategy: screening for high cholesterol and prescribing statin drugs to those who have it, says Ridker. That's pretty good, he says, but since 50 percent of all heart attacks occur in people with normal cholesterol levels, many people at risk aren't identified. But now, he says, "even if your cholesterol is low, [we can] screen for CRP and treat with a statin." (Ridker has received funding from AstraZeneca and is listed as a coinventor on CRP-related patents held by Brigham & Women's.)
So what are the implications for men? Since CRP and the inflammation it measures seem to be important aspects of one's cardiovascular risk, should all men 50 and older have their CRP levels checked and start taking Crestor if their numbers are elevated? Well, no, says Nissen.
The FDA now says that Crestor should be prescribed for prevention's sake in men ages 50 and up and women 60 and older with normal "bad" cholesterol levels only if they have a CRP of 2 mg/L or higher as well as at least one characteristic that puts them at risk for cardiovascular disease. Those risk factors include a smoking habit, a family history of early heart disease, high blood pressure, and low levels of HDL, or "good," cholesterol (which the American Heart Association says for men is anything below 40 mg/dL). By contrast, Jupiter participants did not need any additional risk factors to be eligible for the trial; an elevated CRP level was sufficient, says Ridker.
An FDA Q&A says the trial showed no evidence that Crestor benefited people with no traditional signs of cardiovascular risk except elevated CRP, and thus it shouldn't be prescribed to them. That means a 55-year-old man who smokes but has low levels of LDL cholesterol may want to know what his CRP is, says Nissen, since it might point to a change in treatment. But if a man of the same age has multiple risk factors and high cholesterol, "I'm going to treat him with a statin anyway," says Stuart Seides, associate director of cardiology at the Washington Hospital Center in the District of Columbia, so a test wouldn't change anything.
Note, too, that the CRP test isn't perfect. "You don't want to treat someone with a statin just because they have an isolated CRP increase," says James Stein, director of preventive cardiology at the University of Wisconsin Hospital and Clinics. “There are a lot of things unrelated to heart disease that can make your CRP go up,” including an injury or infection, a dental cleaning, strenuous exercise like a marathon, and even an allergic reaction to a girlfriend’s cat. And the test can be quite variable from week to week. "I would not say the sky is falling if a patient comes to me and says, 'I'm perfectly healthy, but my doc just told me I had an elevated CRP, [so] when am I going to have my heart attack?' " says cardiologist Thomas Behrenbeck, an associate professor at the Mayo Clinic. He said he would have to rule out all the other possible causes before considering cardiac risk. (That's why some guidelines, such as those jointly published by the American Heart Association and the Centers for Disease Control and Prevention in 2003, for example, advise that when doctors deem the test is warranted, they measure CRP twice, ideally two weeks apart, and average the results.)
Also, Crestor isn't cheap. A month's supply of the 20-mg daily dose used in the Jupiter trial now has a retail price of about $141—up about 20 percent since the trial results were published, says Stein. (He used drugstore.com to determine those figures.) That makes Crestor the most expensive statin on the market, he says. Most other statins are available generically.
The key question is whether people could get the same protective benefit from a generic statin as from Crestor, says Nissen, but that will be hard to answer. (Nissen accepts no funding from the pharmaceutical industry.) Some doctors will feel comfortable only if they stick to the FDA's new indication, while other doctors may figure that a statin is a statin is a statin; it's just a matter of finding an equivalent dose. (Crestor is the most potent statin.) "This is where you have to really trust your doctor, do a gut-check, and ask yourself, 'Am I willing to pay more for the proven drug or pay less for a drug that's been proven to do a lot of good things but not exactly what Crestor has been proven for?' " says Stein.
While statins are generally quite safe, say experts, as with any drugs they have side effects. A meta-analysis of 13 statin studies published last month in the Lancet found the drugs were linked with a small but increased risk (9 percent) of getting diabetes, though it wasn't clear why; the authors said that risk was "outweighed by cardiovascular benefit . . . in individuals for whom statin therapy is recommended."(The Jupiter study also reported a slightly higher risk of diabetes.) Some people experience muscle aches while taking the drugs, and extremely rarely, statins have led to rhabdomyolysis, a serious condition in which muscles essentially turn to mush and leak into the bloodstream, endangering the kidneys. Such side effects are why it's important that the benefits of taking a statin like Crestor eclipse the risks, and why "the whole idea of putting statins in the drinking water and everybody just taking it because 'What the hell,' is a really, bad idea," says Seides. Still, he suspects that there will be "some creep" in terms of statins being prescribed off-label to people who don't meet the FDA's new criteria as part of aggressive prevention strategies.
None of this, of course, is a substitute for making and sticking to lifestyle changes. That means following a Mediterranean-style diet,or another healthful eating pattern that's rich in fruits and vegetables, whole grains, fish, and healthy "good" fats (such as olive oil) rather than a steady stream of burgers and fries, says Stein. It also means exercising at least 30 minutes a day rather than using that elliptical machine in the basement as a clothes hanger, he says. And when it comes to medication, none of this new information will be relevant if men don't regularly see a doctor who can help them apply it. Seides himself admits he got a colonoscopy only because his wife made him.
Corrected on 3/2/10: An earlier version of this article incorrectly listed abdominal obesity as a factor unrelated to heart disease that can elevate CRP. Abdominal obesity is related to heart disease.