FDA Panel Recommendation on Crestor Spurs Debate

Dec. 16, 2009— -- A U.S. Food and Drug Administration panel's recommendation that some adults with no prior heart problems should take the cholesterol-busting statin Crestor appears to have pitted cardiologists against many primary care physicians over the best use of the popular drug.

At stake in the debate is the health of millions of Americans who, if the recommendation is followed by the FDA, could soon find themselves urged by their doctors to take the drug.

"If the FDA accepts this recommendation, it will expand the number of Americans eligible for statin therapy by millions," said Dr. Steven Nissen, chair of cardiovascular medicine at the Cleveland Clinic.

A number of cardiologists voiced their support of the idea that the drug should be given to men age 50 or older and women age 60 or older who have LDL cholesterol levels of less than 130 mg/L and triglycerides of less than 500 mg/L if the patient also had an elevated blood level of an inflammation marker known as C-reactive protein, or CRP.

"The FDA correctly saw beyond some of the adverse effects that were rare in this very large group," said Dr. Howard Weintraub, clinical director of the Center for the Prevention of Cardiovascular Disease at New York University. "It will hopefully allow easier access to Crestor and will also motivate physicians to be more aggressive in patients at risk and encourage patients to accept the recommendation of therapy."

Another cardiologist, Dr. Christopher Cannon of Brigham and Women's Hospital in Boston, described the recommendation as "outstanding news for people who are at risk but who would not previously known it.

"The treatment can reduce almost in half their risk of a first heart attack or other cardiac event," he said.

Meanwhile, many primary care doctors were far from enthused.

"I disagree completely with this recommendation," said Dr. Lee Green, a primary care doctor at the Department of Family Medicine at the University of Michigan in Ann Arbor. "I don't think that the FDA recommendation is ready for prime time, and extending it would most certainly be bad science and bad patient care."

Many Primary Care Doctors Disagree With Crestor Recommendation

"This is an interesting and in my mind dangerously premature development," said Dr. Michael Good of ProHealth Physicians in Middletown, Conn. "We know that giving statins to any population will lower their heart attack risk, and there are some in the cardiology community who feel that 'we should put it in the water.' However, unlike fluoride, which we do put in the water, statins have considerable side effects and risks. About one in 10 patients experience muscle pain and weakness, some have liver function changes and the statins as a group have many, many drug interactions."

The FDA expert panel voted 12 to four with one abstention to recommend that the potent statin, known generically as rosuvastatin, be approved to prevent heart attacks in people who have no history of heart disease and don't fit the traditional profile of an "at risk" population.

The FDA is not obligated to follow the advisors recommendations, but it often does. If it did so this time, it would mark a first -- a drug normally used to lower dangerously high LDL (bad) cholesterol in people with a history of heart disease or risk factors to develop heart attacks or strokes would be approved for the prevention of heart attacks in healthy people.

The basis for the new indication was the JUPITER study of almost 18,000 men and women, average age 66. The JUPITER trial was sponsored by AstraZeneca, the company that markets Crestor.

All patients in the study had no history of heart disease, but did have an elevated CRP level.

Patients in the study took 20 mg of Crestor or a sugar pill placebo for 1.9 years. At the end of that time, the patients taking Crestor had an average LDL cholesterol of 55 mg/dL-- down from 109 mg/dL when they started the study.

And compared with patients who took the placebo, the Crestor patients had a 44 percent reduction in heart attacks, stroke, need for surgery or stenting to open clogged arteries, or death from heart disease.

For every 25 people treated with Crestor, a heart attack, stroke, or death was prevented.

Weighing Risks and Benefits of Crestor

Those results, according to Dr. Melvyn Rubenfire of the University of Michigan, were a "home run for JUPITER" but it is not clear if the results would be same with another statin.

Noting that the panel's vote was a "somewhat courageous decision", Rubenfire said the "issue now is how the FDA, physicians, and insurers approach the results. That is, 'are all statins the same?' The robustness of the results are unique to Crestor."

But there were some risks associated with Crestor, including 13 deaths due to gastrointestinal disorders in study subjects taking rosuvastatin, and 18 patients reported a "confused state" while taking the drug.

The most troubling adverse event, however, was an uptick in investigator reported new onset diabetes mellitus in the treatment arm, 2.8 percent versus 2.5 percent, or an increased risk of 27 percent.

Although the advisory committee agreed that the benefit of rosuvastatin outweighed the risk, it said that patients should be carefully monitored for diabetes and they admonished the manufacturer to "carefully define the target population in marketing materials."

The debate once again raises the specter of a medical practice which some say does not have evidence to back its necessity – and may even be harmful – but which others say could be life-saving.

It is not the first recommendation to enter this realm. Recently, the debate over the necessity and balance of risks and benefits for mammograms ignited similar controversy with regard to breast cancer screening.

And though doctors' opinions were split largely according to their specialties, the lines between supporters and detractors were not completely clear-cut.

Dr. Merle Myerson, director of the Cardiovascular Disease Prevention Program at St. Luke's-Roosevelt Hospital in New York, disagreed with the conclusions of the panel.

"This is surprising," Myerson said. "The research on CRP is still not conclusive in terms of the benefit and specificity of CRP's predictive value. This approval would open up a huge new category for treatment. My feeling is that this is premature and not substantiated."

Not All Family Physicians Opposed to FDA Panel Recommendation

Conversely, Dr. Randy Wexler, assistant professor of Clinical Family Medicine at Ohio State University in Columbus, applauded the panel's conclusion.

"I believe that statin medications are one of the true magic bullets in treating and preventing cardiovascular disease," he said. I believe that we should be treating more individuals with expanded indications."