PharmaGossip: Should Healthy People Take Cholesterol Drugs to Prevent Heart Disease?

The WSJ Debate

Yes: They save lives, says Roger S. Blumenthal.
No: High cost, little gain, says Rita Redberg.
Read the complete Big Issues: Health Care report .

Heart disease is the biggest killer in the country. But an argument is raging about a popular way of preventing it.

Most of the medical community thinks that a good approach is to prescribe cholesterol-lowering drugs, or statins, to patients who have high levels of so-called bad cholesterol as well as other risk factors—but who are otherwise healthy.

These doctors say that reducing levels of bad cholesterol helps prevent heart disease and extends life. And, they argue, there's a mountain of research that backs up their case.

But there's a vocal minority of doctors that opposes the practice of giving statins to otherwise healthy people. These doctors argue that studies don't show that taking statins leads to longer life, and they say that much of the research into the question is fundamentally flawed.

What's more, these critics say, there's mounting evidence of troublesome side effects, such as diabetes, from statin use. These critics argue that diet and exercise are better ways to stave off heart attacks and strokes.

Yes: They Save Lives
By Roger S. Blumenthal

Good habits like diet and exercise are the foundations of good health—but sometimes they're not enough. Every major medical guideline calls for doctors to prescribe a statin to certain seemingly healthy people with high levels of "bad" cholesterol, which signals elevated risk for a heart attack. Doing so is one of the certainties of life, like the Cubs falling out of the pennant race by Labor Day.

John Hopkins
'Trials have shown reductions in cardiovascular events of 30% to 40% with the use of a statin.' -- ROGER S. BLUMENTHAL

We don't prescribe drugs to otherwise healthy people without rigorous scientific evidence. And, in this case, there is a mountain of high-quality scientific evidence.

Heart disease is an insidious process that takes decades to manifest itself. Risk factors for developing heart disease often go unrecognized and undertreated until it's too late. So, the first manifestation of cardiovascular disease is often sudden cardiac death, heart attack or stroke—which may result in disability or death. A little late at that point to start prescribing statins.

Too Little, Too Late

Yet critics say we should wait until after a patient has gone through one of these life-shattering events before we prescribe a statin. It makes no sense why a medication that slows the progression of hardening of the arteries would be harmful the day or week before a heart attack, but helpful the day or week after a heart attack.

The totality of the available biologic, observational and clinical-trial evidence strongly supports the selective use of statin therapy in adults demonstrated to be at high risk for heart disease. Studies have conclusively shown that statins prolong life and reduce the risk of heart attack, stroke and death in patients with known heart disease. Similarly, they have been shown to do the same in patients without heart disease, but who are at high risk of developing heart disease.

For instance, a study of 6,600 Scottish men who hadn't had heart attacks showed a decrease in mortality rates after five years with statin therapy. Likewise, the recent world-wide Jupiter study of men and women without prior heart disease showed statins significantly decreased the risk of death after two years in people with an average age of 66.

Critics raise a number of complaints about these studies—exaggerated, in my view—but many other large prevention trials of people with multiple risk factors have consistently shown reductions in total cardiovascular events of 30% to 40% with the use of a statin.

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Critics argue that these studies are fundamentally flawed, because we don't follow patients for the rest of their lives to see the total effect that statins have on mortality, instead of just looking at the effect after a few years.

Well, that's correct. Doing a study of that nature would be enormously expensive and unwieldy, and take decades to complete. Instead, researchers use a system, known as meta-analysis, that's a powerful tool in medical research. Doctors combine data from short-term trials and extrapolate their results to make inferences about mortality. The sum of the trials flushes out bias and reduces statistical uncertainty.

For some critics, that still isn't good enough. My answer is that we don't have conclusive evidence that treating certain types of high blood pressure will reduce mortality, either. Yet if we stopped treating it, the rates of future heart attacks, strokes, and renal failure over the next decade would skyrocket. The same logic holds for selective statin use.

On the other hand, most of the charges critics make about statins just aren't supported by any evidence. Most of the claims about side effects, I'd argue, are anecdotal and not backed up by research. To advise against statin treatment based on unproven risks is risky and unethical, especially when we have the potential to prolong life—as well as reducing patient suffering by eliminating needless heart attacks, strokes and bypass surgery.

I totally agree with the importance of making healthy foods affordable and promoting healthy eating patterns and physical activity. And, yes, they're most effective at a young age, when habits are being formed. But this doesn't negate the value of statin use in middle-aged and older people who are very likely to get heart disease because of risk factors.

Critics of statins argue that lifestyle changes are a lot cheaper than drugs. But generic statins cost about $50 a year. Can you get a year's worth of fruits and vegetables for $50?

Systemic Fixes

What's more, the true alternative to statins is more costly than that. Current lifestyles in the U.S. are flawed. We're getting fatter, older and sicker. We must fundamentally restructure our food supply, so that the focus is not on meat and high-calorie, high-fat foodstuffs with little nutritional value. Our cities, our workday and our pastimes must be restructured to promote physical activity and heart-healthy behaviors.

These interventions require time-consuming and controversial policy changes and considerable cost. Until we can sort all of that out, we must rely on proven medications to help us along—especially statins.

Finally, let's dispense with the idea that statins are a moral hazard—that they give patients a false sense of security and lead them to ignore diet and exercise. The patients we see are generally not falsely reassured by their medications. In fact, we often find that the initiation of medication motivates patients because they better realize how serious their cardiovascular risk actually is.

Think of it this way. If your doctor recommended a statin to you because of high risk of heart disease, would you eat more hamburgers because of this safety net or would you try to exercise a little more?

The bottom line is, treatment doesn't have to be all or none—all statin or all lifestyle. The two can be effectively combined to help our patients.

Dr. Blumenthal is a professor of medicine and director of the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease and editor in chief of "Preventive Cardiology—A Companion to Braunwald's Heart Disease." He can be reached at reports@wsj.com.

No: High Cost, LIttle Gain
By Rita Redberg

Heart disease is the leading cause of death in the U.S., and people with higher cholesterol are at higher risk for heart attacks. There's good evidence that people who already have heart disease benefit from cholesterol-lowering medications, or statins. Among those people, statin treatment reduces risk of heart attack and may prolong life.

Anna Larson
'For most healthy people, the data show that statins do not prevent heart disease.' -- RITA REDBERG

But what about healthy people with high cholesterol? Many doctors have taken the evidence from studies of people with heart disease and made a leap of logic: They've treated millions of healthy people with statins to prevent heart disease.

But there's a serious problem with that logic. For most healthy people, data show that statins do not prevent heart disease, nor extend life or improve quality of life. And they come with considerable side effects. That's why I don't recommend giving statins to healthy people, even those with higher cholesterol.

Despite research that has included tens of thousands of people, there is no evidence that taking statins prolongs life, although cholesterol levels do decrease. Using the most optimistic projections, for every 100 healthy people who take statins for five years, one or two will avoid a heart attack. One will develop diabetes. But, on average, there is no evidence that the group taking statins will live any longer than those who don't.

Some argue that clinical trials of statin use among healthy people haven't demonstrated a reduced mortality rate because each individual trial only follows patients for a few years—not long enough to show a reduction in mortality. Many doctors, including me, believe that we need clinical trials that actually follow healthy people treated with statins for the long term to see if treatment really results in lower mortality. Statin proponents think such trials would be prohibitively expensive. That's a disappointing stance, considering the billions that have already been spent on statin prescriptions and advertising.

Boosters of statins argue that I'm setting the burden of proof too high. But the examples they use—don't we treat high blood pressure without proof of decreased mortality?—actually do have strong evidence on their side. Statins don't.

And many individual studies that statin boosters claim as success stories are flawed. One large study, conducted in Scotland, showed a reduction in mortality among men who used statins for a few years. The study, though, looked at a high-risk group of men for whom the benefits of statins were most likely to outweigh the risks; most were smokers and obese, and some had heart disease. Those results can't be extrapolated to most Americans taking statins today.

Another well-publicized study that showed good short-term results among healthy people taking statins, the Jupiter trial, remains controversial. The results have been questioned by many experts, who note anomalies in the reported findings and strong conflict-of-interest issues for the sponsor and investigators.

Some statin supporters argue that even if the data don't support the benefits of statins in healthy people, they might help and can't hurt. But that's untenable, because statins undeniably harm some people. Besides increasing the risk for developing diabetes, statins can cause memory loss, muscle weakness, stomach distress, and aches and pains. These aren't merely anecdotal results, as some critics assert; they're documented by recent studies.

Until and unless further persuasive evidence is available that the benefits of statins outweigh the known side effects, their use should be limited to patients with known heart disease to help prevent recurrent heart attacks. Even for this population, physicians should disclose that statins likely won't extend their life.

Fortunately, there is a proven, widely available treatment for people at high risk for heart disease that does prolong survival. This treatment is cheaper and more effective than any statin or other known drug, with virtually no adverse side effects. The treatment, which has been available for decades, involves almost no additional costs to patients, insurance companies or the government. Numerous studies have shown dramatic results in not only lowering cholesterol, but in preventing heart attacks and in prolonging life.

This treatment is proper diet and exercise. If we were to spend a small fraction of the annual cost of statins on making fruits and vegetables and physical activity more accessible, the effect on heart disease, as well as high blood pressure, diabetes, cancer and overall life span, would be far greater than any benefit statins can produce.

The effort is entirely feasible, but it requires commitment on many levels—by both physicians and public-health officials. Efforts should start in the school system through, for example, increased physical education and continued improvement in the nutritional value of school lunches and snacks.

Some statin supporters argue that lifestyle improvements alone can't lower cholesterol. But we need to stop confusing lower cholesterol with clinical outcomes. Logic is not evidence, and there's just no evidence that statin treatment extends life among healthy persons.

Indeed, statins present a moral hazard, since some people will make less effort to follow a healthy diet and get regular physical activity because they feel falsely reassured by their medications.

It comes down to this: Before prescribing any drugs to a healthy person, doctors should be able to assure them that the drug will help them to live longer or feel better. Such evidence is particularly important when prescribing drugs that will need to be taken for many decades and have significant associated adverse events, such as statins.

Statins don't meet that standard of evidence. I can't in good conscience recommend them.

Dr. Redberg is a professor of medicine and director of women's cardiovascular services at the University of California, San Francisco. She can be reached at reports@wsj.com.