Statins Prevent Heart Deaths in Low-Risk People

A large study has found the cholesterol pill Crestor significantly lowered the chance of death and heart attack among people with low cholesterol and no substantial risk factors for heart disease.

The study, published online by the New England Journal of Medicine, provides the most compelling evidence to date for using a new test to identify those who may need treatment, said Dr. Elizabeth Nabel, director of the National Heart, Lung and Blood Institute. 

Experts reviewing current guidelines will also consider the new research.

For now, the findings have been praised as a watershed event in heart disease prevention, with doctors saying it may lead an additional 7 million more Americans to begin taking cholesterol-lowering statins such as Crestor, Zocor, Lipitor and the generic form of the drug. Crestor, made by British-based AstraZeneca PLC, is currently the strongest statin on the market.

“This takes prevention to a whole new level, because it applies to patients who we now wouldn’t have any evidence to treat,” Dr. W. Douglas Weaver, president of the American College of Cardiology, told the Associated Press.

However, some experts are urging caution, calling the idea of treating low-risk people “a difficult sell”. They say that while Crestor provided clear benefit in the study, so few heart attacks and deaths occurred among these low-risk people that treating everyone like them in the U.S. could cost up to $9 billion a year.

About 120 people would have to take Crestor for two years to prevent a single stroke, heart attack or death, according to Stanford University cardiologist Dr. Mark Hlatky, who wrote an editorial accompanying the study.

“Everybody likes the idea of prevention. We need to slow down and ask how many people are we going to be treating with drugs for the rest of their lives to prevent heart disease, versus a lot of other things we’re not doing,” he said.

Statins are the world’s top-selling drugs. Until now, all but Crestor had been shown to reduce the risk of heart attacks and death in those with high levels of LDL cholesterol.

However, since half of all heart attacks occur in those with normal or low cholesterol, doctors have been looking for other ways to assess risk.

One way is by performing an $80 blood test to determine levels of high-sensitivity C-reactive protein, or CRP. It is a measure of inflammation, which can indicate clogged arteries as well as less serious problems, such as injury or an infection.

Dr. Paul Ridker of Brigham and Women’s Hospital in Boston, a co-inventor on a patent of the test, led the new study.

A co-inventor on a patent of the test, Dr. Paul Ridker of Harvard-affiliated Brigham and Women’s Hospital in Boston, led the new study, which involved 17,802 participants with high levels of CRP and low LDL cholesterol in the U.S. and 25 other countries.

One-fourth were Hispanic or black, and 40 percent were women, an important distinction since previous studies with statin have not included significant numbers of women. The men were 50 or older, while the women were 60 or older. None of the participants had a history of diabetes or heart disease.

Each participant was randomly assigned to take either a placebo pill or Crestor, with none of the doctors or participants aware who was taking which.

The study was supposed to last five years but was halted in March, after about two years, when independent monitors noticed that those taking Crestor were faring much better than their counterparts taking dummy pills.

The study’s full results were announced Sunday during an American Heart Association conference. They showed that Crestor reduced a combined measure of heart attacks, strokes, heart-related deaths or hospitalizations or the need for an artery-opening procedure, by 44 percent.

“We reduced the risk of a heart attack by 54 percent, the risk of a stroke by 48 percent and the chance of needing bypass surgery or angioplasty by 46 percent,” Ridker said.

Viewed another way, there were 136 annual heart-related problems for every 10,000 people taking dummy pills compared with only 77 for those taking Crestor. Amazingly, every subgroup benefited from the drug.

“If you’re skinny it worked, if you’re heavy it worked. If you lived here or there, if you smoked, it worked,” said Ridker.

AstraZeneca funded the study, and Ridker acknowledged that he and other authors have consulted for the company and other statin makers.

One note of concern in the study was the fact that more people in the Crestor group saw their blood-sugar levels rise or became newly diagnosed with diabetes.

Dr. Sidney Wolfe of the consumer group Public Citizen said that Crestor also has the highest rate among all the statins of a rare but serious muscle condition. And there are probably safer and less costly ways to get the same benefits, said Wolfe, who has campaigned against the drug in the past.

“It is highly unlikely that (the benefits are) specific to Crestor,” Wolfe told the AP. 

Crestor costs $3.45 a day compared with less than a dollar for generic drugs.

Drs. James Stein and Jon Keevil of the University of Wisconsin-Madison used federal health statistics to estimate that 7.4 million Americans, or more than 4 percent of the adult population, are similar to the study’s participants. Treating all of them with Crestor would cost $9 billion a year and prevent about 30,000 heart attacks, strokes or deaths, they calculate.

“That’s pretty costly. This would be a very difficult sell,” said Dr. Thomas Pearson of the University of Rochester, unless a person also had a family history of heart disease or other risk factors.

Pearson co-chaired a joint government-heart association panel that established current guidelines for using CRP tests to determine treatment.

Researchers are not yet sure whether the study’s benefits were due to reducing CRP or cholesterol, since Crestor did both.

However, the study and two other government-sponsored ones reported on Sunday “provide the strongest evidence to date” for testing CRP. Augmenting traditional risk measures with CRP tests could identify millions more people who would benefit from statin treatment, Nabel said in a statement.

U.S. Crestor prescriptions were more than $420 million in the third quarter this year, a 23 percent increase from last year.   In the rest of the world, third quarter sales grew 33 percent to $520 million. Sales of Crestor have been rising despite the availability of generic forms of Zocor and Pravachol.