MCT News Service
March 9, 2009
The benefit was so pronounced - a 54 percent reduction in heart attacks, a 48 percent reduction in strokes and a 47 percent reduction in cardiovascular deaths - that the trial was stopped early after two years, or at about the halfway point.
Surprisingly, the benefit occurred in people who were not considered to be at high risk because they did not have known heart disease and their LDL cholesterol (the bad kind) was at a healthy level - less than 130 milligrams per deciliter and an average of 108 mg/dl.
However, they had higher than normal blood levels of a substance known as C-reactive protein, or CRP, which is a marker for inflammation in the body and an emerging risk factor for cardiovascular disease.
"Now we have hard evidence that these people will live longer," said lead author Paul Ridker, director of the Center for Cardiovascular Disease Prevention at Brigham and Women's Hospital.
Doctors not associated with the research said the landmark study could have important implications for the treatment and prevention of heart disease, expanding statin therapy from high-risk groups to a general population of otherwise healthy people.
The trial involved 17,802 people, men 50 and older and women 60 and older, who got either a placebo or a daily 20 mg dose of rosuvastatin (Crestor), made by AstraZeneca, which funded the trial that was published online in November in the New England Journal of Medicine. It also was presented at the annual meeting of the American Heart Association.
Just how many people in the general U.S. population fit the description of having low LDL cholesterol and high CRP is unclear.
However, an analysis presented at the meeting by two cardiologists from the University of Wisconsin School of Medicine and Public Health suggests that at least 7 million people who otherwise would not be candidates for statin therapy could benefit from going on the drugs because of their elevated CRP.
That could mean nearly 30,000 fewer heart attacks, strokes or deaths each year, according UW cardiologists James Stein and Jon Keevil.
But the benefit would come at a substantial cost, about $9 billion a year, based on a $100-a-month cost for rosuvastatin.
Put another way, it would cost $203,000 to prevent each heart attack or stroke and $480,000 to save one life. However, if a cheaper generic statin, calculated at $5 a month, were used, preventing a heart attack or stroke would cost $10,200 per event and saving a life would cost $24,000.
AstraZeneca, the maker of rosuvastatin, which was approved in 2003, has been looking to show that its drug did something more than simply improve cholesterol levels. Unlike other statins that were approved years earlier, rosuvastatin had not been shown to reduce heart attacks, strokes or deaths.
But with the new research, Crestor, the newest statin to hit the market, becomes the star of the statin universe. Not only did it reduce cardiovascular events in people who normally would be considered at low to moderate risk, the reductions also were considerably more than what had been seen in earlier clinical trials of other statins. Those trials generally showed about a 30 percent reduction in heart attacks and strokes.
The study also showed that the benefit was slightly greater in women, who for years had been under-represented in such clinical trials.
Still, while a 50 percent risk reduction in both men and women seems large, it needs to be taken in the context of the actual number of heart attacks and strokes, which was low, doctors said.
It's still unclear what caused the benefit.
Was the reduction in heart attacks and strokes due to cholesterol lowering, or was it caused by a reduction of inflammation in arteries, one of the so-called pleiotropic effects of statins?
One theory is that as a species, humans did not evolve to live with the high levels of LDL cholesterol found in modern society. Stein noted that hunter-gatherer societies and non-human primates have LDL levels in the 50s, and they do not get coronary disease.
"We need to stop using our own society as a benchmark and recognize that even an LDL cholesterol of 100 mg/dl can be too high if you have other markers of risk like being overweight, increased age and increased blood pressure," he said.
The study likely will change practice for many doctors, especially primary care physicians, said Tim Woods, a cardiologist at Froedtert Hospital in Milwaukee and associate professor at the Medical College of Wisconsin in Wauwatosa.
He noted that half of first heart attacks occur in people with normal cholesterol levels.
"We definitely are having a hard time predicting who is going to have a first heart attack," Woods said. "Cholesterol is not the whole story."
(c) 2008, Milwaukee Journal Sentinel.