TUESDAY, Nov. 15, 2005 (HealthDay News) -- High doses of the cholesterol-lowering statin Lipitor did no better than standard, lower doses of the statin Zocor in preventing recurrent heart attacks and heart-related deaths, a new study found.
However, high doses of Lipitor did reduce the occurrence of some cardiovascular events, including strokes and the need for heart surgery.
There was no difference in mortality between the two groups, according to the study, which was funded by Pfizer Inc., which makes Lipitor.
The findings, set to appear in the Nov. 16 issue of the Journal of the American Medical Association, were released early to coincide with a presentation Tuesday at the American Heart Association's annual meeting in Dallas.
Based on this latest finding, there may still be a benefit to more aggressive statin treatment to further lower levels of LDL or "bad" cholesterol, the authors stated.
Physicians have been reluctant to go with higher doses both because of a lack of evidence and a fear of potential side effects, said study author Dr. Terje R. Pedersen, director of the Center for Preventive Medicine, in Oslo, Norway.
"Now they have the evidence, so I definitely think there will be a trend to use higher doses of statins in the future," he said. "Now we have three trials showing that lower [cholesterol] is better. Right now, in Scandinavia, the high dose is only used by 2 to 3 percent of patients, but I think definitely that will change."
"The borderline nature of the significance, plus previous studies, really provide substantial evidence that lower LDL should be achieved," said Dr. Robert Eckel, president of the American Heart Association and a professor of heart medicine at the University of Colorado College of Medicine in Denver. "This is what I call a tiebreaker. It's not necessarily overwhelming evidence, but it's close enough, and there's no real downside."
Statins have become standard care for people with established coronary heart disease. Zocor, given in 20-milligram doses or 40-milligram doses, is the most commonly used statin in northern Europe, where the trial was conducted.
Lowering LDL cholesterol has been shown to benefit patients with coronary artery disease. The question has been how low to go.
The authors of this study hypothesized that intensively lowering LDL with 80 milligrams of Lipitor would yield more benefit than using the lower dose of Zocor.
"We wanted to compare the gold-standard strategy for prevention with a new strategy, where we tried to reduce LDL cholesterol as much as possible using the highest available dose of [Lipitor]," Pedersen said. "We anticipated that this would provide further benefit in terms of reduction in cardiovascular events because the LDL cholesterol reduction capacity is greater than Zocor."
Almost 9,000 mostly male patients 80 years of age or younger from 190 sites in northern Europe were randomized to receive the most widely used dose of Zocor (20 milligrams) or a high dose of Lipitor (80 milligrams). All participants had suffered previous heart attacks. The median follow-up was almost five years. The study was open-label, although the end points were blinded.
Drugs were partially funded by government agencies in five of the countries and by the patients themselves, Pedersen said.
During the trial, the mean blood levels of LDL were 104 mg/dL in the Zocor group and 81 mg/dL in the Lipitor group.
Treatment with high-dose Lipitor resulted in a 23 mg/dL lower LDL level, which corresponded to an 11 percent reduction in coronary heart disease death, heart attack or cardiac arrest with resuscitation. This was not statistically significant.
When stroke was added to the mix, however, the difference rose to 13 percent. And when factoring in any cardiovascular event, including revascularization, there was a significant 16 percent reduction.
Participants taking Lipitor were more likely to discontinue the drug due to adverse events.
According to the authors, more intensive statin therapy might prevent 63 cardiovascular events per 1,000 patients over five years.
More information
For more on statins, head to the American Heart Association.
