Analyzing a New Prescription for Cardiovascular Disease
By Kathleen Yount
If you don’t already have a bottle of statins in your medicine cabinet, there could be one in your future. This class of cholesterol-lowering drugs has been so successful in treating millions of Americans with high cholesterol and heart disease that momentum is gathering to broaden its use: In March, the pharmaceutical company AstraZeneca secured the government’s permission to market its statin medication, rosuvastatin (Crestor), to some groups of people who don’t even have high cholesterol.
The move was prompted by a 2008 study called JUPITER, which showed that taking rosuvastatin reduced participants’ risk of death by 20 percent. The drug also reduced the incidence of major cardiovascular events in men 50 years and older and women 60 years and older who had “near optimal” LDL—a.k.a. “bad”—cholesterol levels (less than 130 mg/dL) and no history of cardiovascular disease or diabetes, but did have elevated levels of high sensitivity C-reactive protein (see “Do You Need a Statin?”).
The interpretation of the JUPITER study results has been hotly debated in the scientific community. Some say the effects are statistically significant but don’t have much clinical impact for people at normal risk. Others, such as UAB cardiologist Vera Bittner, M.D., argue that many people who do not fall into a high-risk category in the near term still have a significant lifetime risk of heart disease, and that early medical intervention could be the key to preventing premature death and disability in these populations.
Bittner says that there’s good reason to consider broadening the prescription of statins: Our nation is at higher risk for cardiovascular disease than we think it is.
High, Low, or In Between?
Thirty-five percent of patients who develop heart disease have total cholesterol levels under 200 mg/dL, which is considered normal. “I would argue that our current definition of high cholesterol is not correct,” Bittner says. “More than half of all first heart attacks occur in people whose LDL cholesterol levels are below the level at which physicians would prescribe statin drugs.” She says that our definitions of what constitutes “high cholesterol” are likely set too high—especially considering that other primates and human hunter-gatherer populations have total cholesterol levels that are much lower than ours: 100 to 120 mg/dL..
The New Multivitamin?
Clinical trials in India are testing a bold preemptive swipe against heart disease: a “polypill” that combines very low doses of several medications—a statin, three blood pressure medications, and aspirin—and could be given to the population at large, much like a multivitamin. The idea of combining medicines in one pill isn’t new; several drugs now available combine blood pressure medications or pair blood pressure medicine with a cholesterol-reducer. UAB cardiologist Vera Bittner, M.D., explains that part of the rationale for these multidrug combos is improving patient adherence: The more complicated a person’s medication regimen becomes, the less likely that person is to take all of his or her medications properly. Bittner herself is currently involved in two trials that are studying the efficacy of cholesterol medications, one that combines a statin with niacin and one that combines a statin with a new drug that raises HDL (a.k.a. “good”) cholesterol levels. But she says that the polypill concept goes well beyond combining drugs—and that she would want to see results from a clinical trial with hard endpoints before she could endorse it.
Add to that the aging baby boom generation—whose rate of heart disease is no higher than previous generations, but whose sheer numbers are sure to stress our health-care infrastructure. And then there are the millions of young Americans struggling with obesity, type 2 diabetes, hypertension, and abnormal lipid profiles, many of whom could develop heart disease at relatively early ages.
Atherosclerosis, the narrowing and hardening of the blood vessels that is the hallmark of coronary heart disease, begins as early as childhood, Bittner notes. Cholesterol levels also begin to climb many years before a person is likely to suffer a heart attack, stroke, or other event. So a more effective approach to prevention may be to have patients start taking statin drugs at these earlier stages, before the damage is done, Bittner says.
Weighing the Risks
Statins are already a proven therapy for people with heart disease, so what’s the big deal about using them to prevent heart disease in the first place? For one thing, statins—like any other drug—have side effects. Some people who take them suffer recurrent muscle pain; for others the drugs can cause liver-enzyme abnormalities. A new study published this February in the British medical journal The Lancet showed a slight increase in the risk of type 2 diabetes—itself a major risk factor for heart disease—among people taking statins.
A further issue is that people who start taking statins will likely have to continue taking them for years—perhaps for life. But while there is no study data on the effects of taking statins for decades, Bittner notes that there also has been no evidence of harm from clinical trials (which typically last five years) or on subsequent follow-up studies of the patients enrolled in those trials. She argues that the benefits of increasing statin use certainly appear to outweigh the real but relatively small risks.
Statin prices have fallen steadily in recent years, which makes the prospect of long-term use financially feasible for more people. Although Crestor currently costs about $3.50 per day, several statin drugs are now available for little more than 10 cents per pill. A 2009 study in the Annals of Internal Medicine estimated that when statin costs fall below a dime per pill, the U.S. health-care system would actually see a net cost savings if everyone with LDL cholesterol levels over 130 mg/dL got a prescription. (The savings would come from the projected drop in cases of cardiovascular disease, and the costs associated with treating those patients.)
Into the Unknown
Much of the debate over statins reflects a broader scientific quandary: We still do not truly understand all the mechanisms that underlie heart disease, and despite hundreds of large, well-run studies, the evidence supporting current treatments—from drugs to surgical procedures to lifestyle management—is not sufficient to tell doctors how best to reduce the incidence and deadly outcomes of the disease.
According to recent research, 88 percent of Americans have at least one risk factor for heart disease, and most of us have more than one. “So the question is,” Bittner says, “do you just let all those people live out the consequences, or do you step in and try to intervene?”
Virtually all researchers agree that lifestyle—whether it’s smoking, diet, exercise, or stress—plays a central role in reducing or increasing risk of heart disease. They also agree that it’s very difficult for most people who have risky behaviors to achieve and maintain positive behavior changes. Some argue that another pill-based solution only distracts from efforts to encourage behavioral changes such as improving diet and exercising.
These low-tech, low-cost approaches to heart disease are indeed the most appealing long-term strategy, says Bittner. “In an ideal world, I would agree that lifestyle should be our main focus.” The problem is, well, reality. “Adherence to lifestyle change is poor in many people. I just don’t feel comfortable saying to today’s population, ‘Just keep on working on exercise and diet, and eventually your cholesterol will look better.’ A lot of people will not survive to the point where they would actually reap the benefits of the small lifestyle modifications that they’re willing to make.”
Do You Need a Statin?
New guidelines for lipid-lowering therapy are currently under development at the National Institutes of Health. But opinions about when to prescribe a statin will likely continue to vary from physician to physician and insurance company to insurance company, says UAB cardiologist Vera Bittner, M.D. According to the JUPITER trial criteria, preventive use of statins may be the right choice for people who match these risk factors, even with normal LDL cholesterol levels:
• men older than 50 or women older than 60;
• High sensitivity C-reactive protein (hs-CRP) levels greater than 2 mg/L; and
• at least one additional heart disease risk factor, such as high blood pressure, low HDL (a.k.a. “good”) cholesterol levels, smoking, or a family history of early heart disease.