Statin Drugs: Heart Benefits Last Long

Cholesterol-Lowering Drugs Turn Back Clock on Heart Disease

From the WebMD Archives

Oct. 10, 2007 -- Men who took statins for five years had fewer heart deaths and heart attacks 10 years later -- even though most had stopped taking the cholesterol-lowering drugs.

The intriguing finding suggests that relatively small, early reductions in bad LDL cholesterol can have very large benefits later in life.

Study investigator Stuart Cobbe, MD, professor of medical cardiology at the University of Glasgow, Scotland, says the finding was something of an accident.

"Almost by chance we had the opportunity to look at the long-term effect of a five-year period of treatment with statins -- without further ongoing treatment -- to see how that altered the trajectory of heart disease," Cobbe tells WebMD.

What happened?

"The very interesting finding is the five-year treatment had a beneficial effect that was clear 10 years later," Cobbe says. "We put the clock back on coronary disease in the people who received treatment."

These results, taken together with other recent findings, are very exciting to Michael Domanski, MD, chief of the atherothrombosis and coronary artery disease branch of the National Institutes of Health. Domanski's editorial comments accompany the study by Cobbe and colleagues in the Oct. 11 issue of the New England Journal of Medicine.

"If you start early, and keep LDL cholesterol down over a lifetime, you may be able to prevent heart disease," Domanski tells WebMD.

Lower LDL Cholesterol = Less Heart Disease, Death

The study by Cobbe and colleagues, called the West of Scotland Coronary Prevention study, enrolled 6,595 middle-aged men with high cholesterol from 1989 through 1991. None of the men in the study had a previous heart attack.

It was supposed to test a then-new idea: that Pravachol, one of the cholesterol-lowering statin class of drugs, might prevent heart disease (other statins available in the U.S. are Crestor,Lescol, Lipitor, Mevacor, and Zocor). At the time, statins were prescribed only for patients who already had heart disease.

Pravachol treatment cut their average LDLcholesterol levels by 26% -- from 192 mg/dL to 142 mg/dL. Over the five-year study period, these men had 31% fewer heart attacks or deaths from heart disease.


Because most doctors still thought statins should be prescribed for men with existing heart disease, fewer than 40% of the men used statin drugs after the study ended. Nevertheless, the researchers kept tabs on the men for another 10 years.

This gave them the chance to see whether statin treatment had any lasting benefit. It did. Men who got inactive placebo pills during the study had a 15.5% chance of heart attack or heart death 10 years after the study ended. Those who got five years of statin treatment had only an 11.8% chance of heart attack or heart death. They also had a lower risk of heart disease.

This doesn't mean that the men should have stopped taking statins. Although five years of treatment offered a long-lasting benefit, the men's heart attack and heart death rates were much lower during the time they were taking their medicine.

"This suggests to us that although the benefit of those years was not lost, one would continue to get benefit from taking the statins," Cobbe says.

The study eased concern that statin treatment might increase cancer risk.

"There has been a long-running controversy over whether statins increase other diseases. The one that has generated the most discussion is whether these drugs increase the risk of cancer," Cobbe says. "Here we have a chance to see the effect on cancer a decade after treatments were finished. And we saw no evidence at all of a cancer effect."

An End to Heart Disease?

It's not the first time a study has suggested that early reductions in LDL cholesterol prevent heart disease. NIH researcher Domanski points to a 2006 study that looked at people with rare mutations in a gene called PCSK9.

The PCSK9 gene encodes a molecule that reduces the number of LDL cholesterol receptors in the liver. Think of these receptors as cholesterol drains. They are the main way the body gets rid of bad cholesterol. The more of these receptors a person has, the lower that person's LDL cholesterol level.


The 2006 study showed that people who carried certain PCSK9 gene variants had somewhat lower cholesterol levels than people with normal PCSK9 genes -- 28% lower LDL for one gene variant and 15% lower LDL for another variant.

But because they had these relatively modest LDL cholesterol reductions from the time they were born, people who carried the gene variants had far lower risk of heart disease -- 88% lower risk for one gene variant, and 47% lower risk for the other.

Moreover, Domanski points out, heart disease is almost unknown in people who live in hunter/gatherer societies that traditionally consume few saturated fats. Once these people adopt modern lifestyles, however, they have the same risk of heart disease as people living in Western cultures.

"It is a very different thing to prevent heart disease than to prevent cardiac events in people who already have heart disease," Domanski says. "If you started lowering LDL cholesterol early -- before someone has coronary artery disease -- you could get very big effects. The potential of LDL lowering, instituted early in life needs, much more research."

Domanski isn't suggesting that we put statin drugs in the water supply. But he does think a clinical trial of statin drugs, in a healthy group of people 30 to 40 years old, is worth the effort. If modest LDL cholesterol reduction early in life could cut heart disease by 50% or more, the impact would be huge.

"Dr. Domanski's very interesting suggestion is that if you were to start treatment earlier, the benefit of preventing heart disease would be greater than the benefit seen by starting at middle age," Cobbe says. "The opposing argument is you would end up medicalizing very, very large sections of the population, with potentially a quarter or a third of all adults being on statins."

Domanski says the answer to cholesterol lowering need not be statin drugs. Lifestyle changes can have just as big an effect. And new generations of cholesterol-lowering drugs -- including drugs that target PCSK9 -- are on the horizon.

WebMD Health News Reviewed by Louise Chang, MD on October 10, 2007


SOURCES: Ford, I. New England Journal of Medicine, Oct. 11, 2007; vol 357: pp 1477-1486. Domanski, M.J. New England Journal of Medicine, Oct. 11, 2007; vol 357: pp 1543-1545. Cohen, J.C. New England Journal of Medicine, March 23, 2006; vol 354: pp 1264-1272. Shepherd, J. New England Journal of Medicine, Nov. 16, 1995; vol 333: pp 1301-1307. Stuart Cobbe, MD, professor of medical cardiology, University of Glasgow, Scotland. Michael Domanski, MD, chief, atherothrombosis and coronary artery disease branch; and clinical trials scientific research group leader, Prevention and Population Sciences Division, National Institutes of Health, Bethesda, Md.

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