Drug Is Found to Unclog Arteries
Intensive doses of a cholesterol-lowering statin drug have for the first time cleared sticky plaque lodged in arteries, opening the possibility of a nonsurgical method of treating the major cause of heart attacks, researchers reported Monday.
The results were seen in a study of 500 patients taking the highest recommended dosage of Crestor -- 40 milligrams -- quadruple the typical starting dose of 10 milligrams.
Although the study looked only at Crestor, produced by European drugmaker AstraZeneca, experts said it was likely that high doses of other statin drugs also would remove blockages from arteries because the medications were similar.
Some researchers criticized the study because it did not compare the Crestor patients with a control group taking a placebo or other cholesterol-lowering pills. Such studies are the gold standard in research because they reduce the possibility of bias.
More research is needed to show that a reduction in plaque lowers the risk of heart attack, said Dr. Steven Nissen of the Cleveland Clinic, the researcher who led the study published online Monday by the Journal of the American Medical Assn.
Several other drug companies and the National Institutes of Health are conducting similar trials on other statins. The first results are expected by early next year.
“A lot of us thought this couldn’t be done,” said Nissen, who presented his findings at a meeting of the American College of Cardiology in Atlanta, calling the results “shockingly positive.”
“The use of such high doses of Crestor raised concerns about the drug’s side effects, which include possible muscle and liver damage, although no patients in the two-year study suffered serious problems.
However, one-third of patients had an increased buildup of plaque, researchers said.
But some doctors said the results were so encouraging that the risks could be worth it for many patients in the early stages of arteriosclerosis, or hardening of the arteries induced by excessive cholesterol.
“If you can regress or reverse arteriosclerosis, what can be better than that?” said Dr. Howard K. Elkin, a Whittier cardiologist.
Arteriosclerosis affects an estimated 13 million Americans. As the coronary arteries harden and narrow, less blood moves through them and the flow to the heart is reduced.
Surgical procedures are used to reopen or bypass clogged blood vessels. Typically, the operations are used to treat patients with an artery that is more than 50% blocked with plaque.
Statins, taken by an estimated 20 million Americans, are used to slow down the buildup of plaque to prevent or reduce the chance of heart attack.
Although previous studies had hinted that other cholesterol-lowering drugs might reduce plaque, the tests were too small to be given much weight.
The international study was funded by AstraZeneca and involved 507 patients with early stages of atherosclerosis.
Nissen said that although the study was funded by the drug company, he had complete control of the trial’s design and its data.
Patients received 40 milligrams of Crestor daily. All patients in the study had at least one arterial obstruction and a 20% narrowing of an artery because of plaque.
None of the patients had taken a cholesterol-lowering drug for more than three months in the year before they entered the study. Patients were excluded if they had poorly controlled diabetes.
Researchers used a catheter with a tiny camera attached to measure plaque in a specific blood vessel segment before and after the experiment. Overall, the average reduction in plaque was about 9%.
Nearly two-thirds of patients had increased blood flow in the artery being studied because of a reduction in plaque.
Researchers said the plaque reduction resulted from lowering patients’ cholesterol.
Patients in the study saw their bad cholesterol counts drop 53% from an average of 130.4 milligrams to 60.8 milligrams per deciliter of blood, the lowest point yet in a clinical trial.
Good cholesterol counts rose about 14% from 43.1 milligrams to 49 milligrams.
Although the study looked only at heart disease patients, the results seemed to move the goal line for cholesterol counts. Currently, bad cholesterol counts below 100 milligrams are considered acceptable for most people. Patients with heart disease are encouraged to lower bad cholesterol counts to below 70 milligrams.
But researchers said one lesson from the study was that lower was better when it came to bad cholesterol.
“We concluded that if you lowered [bad] cholesterol to very low levels for two years, you could reduce plaque in a very sizable way,” Nissen said
Despite the study’s overall good results for statins, a sizable portion of patients did not improve. Nissen said blood samples taken from patients would be analyzed for clues to why some patients responded differently to the drug regimen.
Crestor is considered to be one of the most powerful of the statins. Its maximum 40-milligram dose is half of the maximum approved for other popular statins, such as Pfizer Inc.'s Lipitor and Merck & Co.'s Zocor.
Safety concerns have dogged Crestor since it was approved in 2003. A variety of studies have come to conflicting conclusions on the drug’s safety.
Crestor’s 40-milligram dose is recommended only for those who don’t meet their cholesterol goals on lower doses. The product label cautions patients to weigh the possible risks of muscle damage against the potential benefits. Researchers said no cases of severe muscle damage were reported in the study. Nineteen patients, or 3.7%, quit the study complaining about muscle pain and weakness.
Asians are advised to take no more than 20 milligrams because of poorly understood genetic factors.
Dr. Sidney Wolfe of the Washington watchdog group Public Citizen said he was concerned that the study would lead to increased prescribing of the highest dose of Crestor.
In an editorial published online Monday by the Journal of the American Medical Assn., Dr. Roger S. Blumenthal of Johns Hopkins Medical School said the study also did not address whether the highest dose of Crestor was needed to reduce blockages.
Nissen said that it would have been unethical to give heart disease patients a placebo or lower dosages. He also said that a study that compared Crestor with another drug would have been expensive and it was unlikely that a drug company would fund such a trial because of the risk of its drug looking bad.
Another unanswered question is what happens to blockages when patients take high doses of cholesterol drugs for longer periods.
“If we continued for five years instead of two, could we get to 50 [milligrams]?” Nissen said. “How much plaque could we get rid of? How far can we turn back the clock on disease?”