MONDAY, March 13, 2006 (HealthDay News) -- Scientists may have succeeded in turning back the clock in patients with heart disease.
Intensive cholesterol-lowering therapy using Crestor -- a powerful (and controversial) member of the statin family of drugs -- not only reduced LDL or "bad" cholesterol levels but actually reversed atherosclerosis, better known as hardening of the arteries.
The researchers presented the findings Monday at the annual meeting of the American College of Cardiology (ACC), in Atlanta.
"It is a turning point and it is an achievement we've long sought and we're obviously thrilled," said study lead author Dr. Steven Nissen, interim chairman of the department of cardiovascular medicine at the Cleveland Clinic and president-elect of the ACC. "We think it's good news for patients because it means that we can, with very, very low levels of LDL, get to the point where we're removing some of the plaque from the coronary artery, and that's a pretty good thing."
It's still unclear, however, if changes in the amount of plaque build-up in the artery actually correlate with fewer cardiac events or if other types of cholesterol-lowering drugs or steps would show the same benefit.
"It's a very, very interesting study and potentially very helpful and an important addition to our understanding," said Dr. Sidney Smith, professor of medicine at the University of North Carolina, Chapel Hill, former president of the American Heart Association (AHA) and co-chairman of the ACC/AHA Task Force on Practice Guidelines. "But, in terms of broad treatment recommendations, we really need to see how these findings correlate with outcomes."
"What does this mean, practically speaking? That's the problem," added Dr. Donald Smith, director of lipids and metabolism at the Cardiovascular Institute at Mt. Sinai Medical Center in New York City. "We're stuck with hoping that changes in plaque will make a difference in terms of outcome."
The study appears in the April 5 issue of the Journal of the American Medical Association and is being released early online to coincide with the presentation at the ACC meeting.
Atherosclerosis refers to the accumulation of cholesterol and other substances in the inner lining of an artery. In some cases, this accumulation, called plaque, can become brittle and break off, causing blood clots and possibly even heart attacks.
While lower LDL cholesterol has been shown to reduce the risk of such events, doctors aren't in agreement on how low to go, although, increasingly, evidence suggests that lower is always better.
The introduction of cholesterol-lowering drugs called statins in 1987 brought the hope that atherosclerosis could one day be reversed. That hope, however, has been elusive.
"The closest we came was when we got LDL down to 79, which we thought was fantastic but all we got was no [disease] progression," Nissen said.
For the new trial, 507 patients at 53 health-care centers in the United States, Canada, Europe and Australia were given 40 milligrams a day of Crestor (generic name rosuvastatin). Crestor is the most recently introduced and one of the most potent of the statin family of drugs.
Plaque build-up was measured by intravascular ultrasound (IVUS) at the beginning of the study and two years later. The researchers were able to report information on 349 participants.
Sixty-four percent of the patients showed regression of atherosclerosis, the researchers said.
And the average LDL levels fell from 130.4 mg/dL (milligrams per deciliter of blood) to 60.8 mg/dL, an average reduction of 53.2 percent. HDL ("good") cholesterol levels rose from 43.1 mg/dL to 49 mg/dL, a 14.7 percent increase.
"That's the lowest LDL ever that's been achieved in a clinical trial of this kind," Nissen said. "The 14.7 percent increase in HDL is also unprecedented. With that combination, we saw a large-scale regression, 7 to 9 percent of plaque volume."
"At this point, we can say that if you can get your patients to these very low levels of LDL with an intense statin regimen, particularly if it's accompanied by a major increase in HDL, then you are capable of partially reversing the disease," Nissen added. "That's a step forward."
"It certainly adds to the growing body of evidence to suggest that lower target levels of LDL may have additive value," added Smith, of the University of Carolina.
Still, several questions remain.
One is whether the benefits could be achieved with other statins or other cholesterol-lowering measures.
"My guess would be that the changes would be seen with other degrees of LDL lowering by statins and presumably by other mechanisms which would lower LDL, but we need to confirm it," said Smith.
Also, the study only looked at people who had already suffered one coronary event, such as a heart attack. It's unclear how this strategy would work in people who had not yet suffered such a fate.
There are varying views as to how safe Crestor is compared to other statins. The consumer advocacy group Public Citizen has petitioned the U.S. Food and Drug Administration to take the drug off the market. But in a March 11, 2005, letter to the consumer group's director of health research, the agency concluded, "The available evidence concerning Crestor's safety does not warrant the withdrawal of Crestor from the market."
Public Citizen isn't likely to change its stance, despite the new findings.
"The study is a bit less impressive than perhaps is put forth," said Dr. Peter Lurie, deputy director at Public Citizen's Health Research Group. "Many patients were lost to follow-up, and there is no comparison group, so we have no way of knowing if some other drug might not have accomplished exactly the same thing," he said. "It leaves many questions unanswered. I don't see a fundamental shift here in our position."
Even backers of the findings acknowledge that medical practice won't be altered by the merits of one study.
"Usually a single study doesn't change everybody's practice," Nissen said. "It changes the momentum and, with that momentum, you'll see more interest in this and people reaching lower LDL levels."
For more on atherosclerosis, visit the American Heart Association.