DURHAM, N.C. -- In people who have experienced a stroke, but who have no known history of coronary heart disease, beginning regular treatment with the cholesterol-lowering drug atorvastatin soon after the stroke can reduce the risk of recurrent stroke by 16 percent, according to a five-year study led by an international team that includes a researcher at Duke University Medical Center.
The results of the study, called the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial, appear in the August 10, 2006, issue of the New England Journal of Medicine. The study was funded by Pfizer, the manufacturer of atorvastatin.
"This is the first study to demonstrate that treatment with a statin, a type of cholesterol-lowering drug, can reduce the risk of strokes in patients who have had a recent stroke or a transient ischemic attack and who have no known history of coronary heart disease," said Larry B. Goldstein, M.D., director of the Duke Stroke Center and a member of the SPARCL steering committee.
A transient ischemic attack is similar to a stroke, but is of shorter duration and severity. Often referred to as a ministroke, it is considered a warning sign or prelude for stroke.
"These results will have a major effect on how people are treated following a stroke," Goldstein said. "The findings are very important for physicians and patients because they show that the addition of this drug to other treatments further reduces the risk of another stroke, which is a pretty big step in improving what we can do for stroke patients."
Previous studies, Goldstein said, have demonstrated that atorvastatin and other drugs within the class of medications called statins could reduce risk of stroke in patients who have a history of coronary disease. Coronary heart disease is a narrowing of the small blood vessels that supply blood to the heart, usually due to a build-up of cholesterol. It is a leading cause of death for Americans, he added.
The study results showed that atorvastatin -- sold as Lipitor -- in addition to reducing recurrent stroke risk, can also reduce stroke patients' risk of heart attack and other major coronary events by 35 percent; their risk of cardiovascular events such as unstable angina by 42 percent; and their need for coronary revascularization procedures, such as coronary artery bypass grafting or cardiac catheterization, by 45 percent, compared to treatment with an inactive placebo.
In the trial, the researchers enrolled 4,731 patients at 205 study sites in Africa, Australia, Europe, the Middle East, and North and South America. All of the patients had experienced either a stroke or a transient ischemic attack within six months of their enrollment. The patients averaged 63 years of age; 60 percent were male and 40 percent female. Patients were monitored for an average of five years following enrollment.
At the time of their enrollment, roughly 66 percent of the patients had experienced an ischemic stroke, which occurs when the blood supply to a part of the brain is suddenly blocked; 2 percent had experienced a hemorrhagic stroke, which occurs due to a leaking blood vessel in the brain; and 30 percent had experienced a transient ischemic attack.
Ninety-four percent of the patients enrolled were already being treated with aspirin or medications that reduce clotting of the blood, and 69 percent of the patients, most of whom had high blood pressure, were receiving treatment with blood-pressure lowering medications. Those treatments were continued during the patients' participation in the SPARCL study.
The researchers randomly assigned patients to receive either 80 milligrams per day of atorvastatin or an inactive placebo. The study was double-blinded, meaning that neither the researchers nor the patients knew in advance which patients were receiving the active medication.
The study found that atorvastatin, compared with the placebo, reduced the risk of fatal and nonfatal strokes by 16 percent.
This overall reduction in the risk of stroke was present despite a small increase in the number of patients having one of the types of stroke, hemorrhagic stroke. Due to the small number of people recruited into the SPARCL trial with a previous hemorrhagic stroke, the researchers said that it is not possible to reach any meaningful conclusions regarding their risks and benefits with atorvastatin treatment.
The researchers suggest that the drug appears to exercise its overall protective effect by lowering the levels of low-density lipoprotein (LDL) cholesterol -- popularly known as "bad" cholesterol -- in patients' blood. High levels of LDL cholesterol in the blood are known to increase the risk of coronary heart disease, a risk factor for stroke as well as heart attack.
Patients who received atorvastatin had an average LDL cholesterol level of 73 milligrams per deciliter of blood, compared with an average of 129 milligrams per deciliter for patients on placebo, the researchers said.
The SPARCL study, including the work of the steering committee, was supported by Pfizer. Goldstein also has consulted for Pfizer and other manufacturers of statin medications.
Other members of the SPARCL steering committee, who also were co-authors of the report, include Pierre Amarenco of Denis Diderot University, Paris, France; Julien Bogousslavsky of University of Lausanne, Switzerland; Alfred S. Callahan III of Neurologic Consultants, P.C., Nashville, Tenn.; Michael Hennerici of Universitat Heidelberg, Mannheim, Germany; Henrik Sillesen of University of Copenhagen, Denmark; Justin Zivin of the University of California at San Diego; and K. Michael A. Welch of the Rosalind Franklin University of Medicine and Science, Chicago, who chaired the steering committee. Other co-authors, who are not members of the steering committee, include Amy E. Rudolph, Lisa Simunovic and Michael Szarek, all of Pfizer.