Two earlier studies found that starting statin therapy early reduced the risk of death and second heart attacks. The new one -- the largest of the three -- finds no such reduction overall and a higher risk of death or a second heart attack for people whose cholesterol readings are below the level at which treatment is recommended.
However, the new report is far from the last word, says Dr. L. Kristin Newby, an associate professor of medicine at Duke University Medical Center who reports the results in tomorrow's issue of the Journal of the American Medical Association.Her reason for caution is a distinction familiar to doctors: The new study, like the previous two that reported positive results, was "observational" -- that is, it analyzed data from a trial that was not specifically designed to answer the immediate question.
"The data were collected for different purposes, so there are a number of factors that can be difficult to control for," Newby says. "There may be different types of patient populations, the way other therapies were used, the severity of the condition."
A definitive answer can come only from a randomized clinical trial, one designed in advance to answer a specific question, in which use of a treatment is carefully made and excludes confusing factors, Newby says.
However, the new trial "raises the question of how aggressive we should be with statin therapy, particularly if we do not know the patient's cholesterol level," Newby says. "It raises a caution on how we use these drugs."
Data from the study she analyzed, which included more than 12,000 patients, included cholesterol levels. The analysis showed that patients with levels of LDL cholesterol -- the "bad" kind that clogs arteries -- below 130 had a higher risk of death or a second heart attack if they started statin therapy while they were still in the hospital than if they did not. Guidelines of the American Heart Association and American College of Cardiology recommend dietary and drug therapy for people with levels above 130, but do not recommend that drug therapy be started before discharge from the hospital.
There still is a strong case for starting statin therapy before hospital release, says Dr. Eugene Braunwald, a professor of medicine at Harvard Medical School and co-author of an accompanying editorial. "It is the compliance issue," he says.
Experience shows that despite the clear dangers they face and the careful advice they are given, many people who have had heart attacks often pay little attention to dietary advice and don't take their medicine -- unless they are given the prescription before they leave the hospital, Braunwald says. Being in a hospital, he says, provides "a treatable moment. What is clear is that there will be a huge number of patients on statins six months later if they are started in the hospital."
He, too, is wary of the new results. "What we have is basically two observational studies that appear to show the benefit of early treatment and a very large one which shows absolutely nothing. So, we have to suspend judgment."
A lesson Braunwald draws is that "this shows the risk of drawing far-reaching conclusions from observational studies. They have bitten us before, and will bite us again. It is a cliché to say that the randomized control trial is the gold standard, but it is."
Two such randomized trials that can answer the statin question are under way, and Braunwald is involved with both. "My expectation is that we can report results at the fall meeting of the American Heart Association in 2003," he says.
Meanwhile, Newby says the study has affected the way she treats heart attack patients. "I am more cognizant about knowing cholesterol levels when I think about starting statin therapy early," she says. "I will just be a little more cautious about pushing the window."
What To Do
You can learn about blood cholesterol and heart disease from the National Heart, Lung and Blood Institute. Also, the American Heart Association has a page on preventing second heart attacks and cholesterol-lowering drugs.