Taking very high doses of a drug to push cholesterol to very low levels can help people with heart disease avoid strokes and heart attacks, but also can cause liver problems that limit the ability to tolerate such intensive treatment, doctors report.
A very large international study tested this approach for the first time in people with clogged arteries that occasionally cause chest pain, and found that it cut their chances of having a bad event such as a heart attack by 22 percent compared with those on a lower dose.
The findings "confirm and extend" evidence that this strategy works, conclude the researchers, who were led by Dr. John LaRosa of State University of New York in Brooklyn.
Results were presented Tuesday at an American College of Cardiology meeting in Orlando. They also were published online by the New England Journal of Medicine and will be in its April 7 edition.
The study was funded by and involved many doctors with ties to Pfizer Inc., the maker of Lipitor. It is one of six so-called statin drugs on the market that lower LDL or "bad" cholesterol. Federal guidelines advise people at high risk of a heart attack to get LDL to 70 and for those at moderate risk to aim for 100.
In the study, 10,001 patients in 14 countries took either 10 milligrams or 80 milligrams of Lipitor, bringing their LDL levels to 101 and 77, respectively.
After nearly five years, 10.9 percent of those on the low dose had died or suffered a stroke, heart attack or other big problem compared with 8.7 percent on the high dose — an absolute difference of 2.2 percent, which translated to a 22 percent reduction in risk.
"This is falling into line with what we saw from other trials" involving different types of patients — those who had recently suffered a heart attack, said Dr. Sidney Smith, an American Heart Association spokesman and cardiology chief at the University of North Carolina. He has been a consultant for Pfizer and other statin makers and also helped draft the federal cholesterol guidelines.
But side effects were a concern. About 1.2 percent developed signs of liver inflammation on the high dose versus 0.2 percent of the others. Patients would have to be aggressively tested and monitored for this condition, Smith said.
Results also might vary with a different statin, he said. Other brands are Bristol-Myers Squibb's Pravachol, Novartis Pharmaceuticals' Lescol, AstraZeneca's Crestor, and Zocor and Mevacor, sold by Merck & Co.
In an editorial in the medical journal, Dr. Bertram Pitt of the University of Michigan School of Medicine said it isn't known if aggressively lowering LDL is the best strategy for cutting heart attack risk or that high-dose statins are the best ways to do that. Other approaches, such as raising "good" cholesterol or adding other drugs to conventional doses of statins need to be compared.
More evidence also is needed on using high doses of statins, he wrote. Smith said two other large studies should help provide such answers within a year.
"We need further reassurance as to the safety of this approach before we can advocate a major shift" in cholesterol goals, Pitt wrote.