An estimated 20 million Americans take statins, making these cholesterol-lowering drugs the most widely prescribed class in the world. In coming years, these numbers are only expected to increase. In June 2011 the full patent for Pfizer’s blockbuster Lipitor (atorvastatin) will expire, making the drug significantly more affordable. And later this year the National Cholesterol Education Program (NCEP) of the National Heart, Lung, and Blood Institute will release guidelines that could recommend statins for younger people who have no cholesterol issues—a move that could stave off cardiovascular disease later in life but also introduces questions about aggressively treating the healthy.
The current NCEP guidelines, published in 2001 and revised in 2004, recommend statins for heart disease patients with LDL (“bad”) cholesterol levels greater than 70 milligrams per deciliter of blood and for people who have a moderately elevated risk of heart disease as well as LDL levels above 100 mg/dL. An expected NCEP move to lower the treatment bar this year would follow a Food and Drug Administration advisory panel’s vote in December 2009 to broaden the prescription base of AstraZeneca’s drug Crestor (rosuvastatin) to an additional 6.5 million lower-risk Americans. The FDA usually accepts the panel’s recommendations.
For many doctors, these treatment changes are overdue. With the current guidelines and prescription numbers, “you’re going to miss a lot of the people who were destined to have heart attacks,” says Antonio M. Gotto, Jr., dean of Weill Cornell Medical College. Joseph L. Witztum, an endocrinologist at the University of California, San Diego, argues that people should be treated with statins early in life to achieve and maintain LDL cholesterol levels below 50 mg/dL. “If you start at age 30, when you can prevent even the earliest [cardiovascular] lesions, the lifetime benefits will be really quite astonishing,” he remarks. For instance, people who have low cholesterol their entire lives—such as those born with a mutation in a gene called PCSK9—suffer far fewer heart attacks than people who lower their cholesterol only later in life.
Direct evidence for the benefits of statins as primary prevention—that is, for preventing heart attacks in people who do not yet have heart disease—comes largely from one clinical trial published in 2008 in the New England Journal of Medicine. The trial, called JUPITER and funded by AstraZeneca, enrolled nearly 18,000 subjects without heart disease who had LDL cholesterol levels below 130 mg/dL and elevated levels of the inflammatory marker C-reactive protein. The trial found that rosuvastatin reduced the risk of cardiovascular events by 44 percent as compared with placebo.
Some physicians, however, have doubts as to whether the results extend to the general population, noting that JUPITER’s subjects weren’t healthy at all. More than a quarter were obese, 41 percent had metabolic syndrome and about 16 percent smoked. “They’ve never had a [cardiovascular] event, but that doesn’t meant they’re low risk—it just means they’ve dodged a lot of bullets,” says James Liao, director of vascular medicine research at Harvard Medical School’s Brigham and Women’s Hospital. Although JUPITER describes its subjects as “apparently healthy,” it would be more accurate to consider them at moderate risk of heart disease, notes Richard Karas, a cardiologist at Tufts University. “As with every clinical study, you shouldn’t generalize the finding to people who weren’t eligible for the study,” he says.
Statins can also have side effects, the most common being muscle and joint pain. “Most clinicians will tell you that they see them in at least 5 percent of patients and as many as 20 percent,” says Matthew F. Muldoon, an internist and clinical pharmacologist at the University of Pittsburgh Medical Center. Although the pain is typically mild, symptoms “frequently lead to complaints to the doctor and changes in medication,” he says. A much smaller percentage of patients suffer from severe muscle complications, like rhabdomyolysis.
But even rare side effects can be important when drugs are aggressively used. In 2007 Karas published a study in the Journal of the American College of Cardiology suggesting that the risk of complications increases with statin dose. If more people start taking statins and at higher doses, many more people will experience problems. “It’s one thing to treat a person who’s had a heart attack with a statin drug for five or 10 years, because their likelihood of a vascular event is very high. It’s another thing to take 35-year-olds who have high cholesterol and treat them for 30 years,” Muldoon says. “That’s a whole different argument to make and justify.”
Karas points out that he is not against broader statin treatment. He simply believes that guidelines should reflect existing data. And even if the results of JUPITER do not apply to truly healthy people, that does not mean they are not relevant. “There’s a sizable proportion of the American adult population that has a risk factor profile that’s similar to JUPITER,” Karas says. “If you look out across the U.S., it’s not a very healthy population.”