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March 17, 2009 -- Results from a new study have dashed hopes for the further development of a newer class of cholesterol-lowering drugs to prevent cardiovascular disease.
Researchers say that the drug pactimibe did not slow down the development of clogged arteries ( atherosclerosis) in those with familial hypercholesterolemia, a genetic predisposition to high cholesterol levels. But the drug did increase their risk of heart attack and stroke and may even promote the formation of plaque buildup.
The study is published in this week's edition of The Journal of the American Medical Association.
Pactimibe is a type of drug called an ACAT-1 inhibitor. The drug blocks the action of an enzyme involved in the accumulation of cholesterol within cells. Animal studies showed that pactimibe deterred the buildup of dangerous plaque in the arteries, leading some to hope that ACAT-1 inhibitors could become a new approach for preventing cardiovascular disease.
However, studies in humans have not been as encouraging. For the current study, Marijn C. Meuwese, MD, of the Academic Medical Center in Amsterdam, Netherlands, and colleagues wanted to determine if pactimibe safely and effectively reduced the progression of atherosclerosis in 892 patients with familial hypercholesterolemia. High cholesterol increases your risk for atherosclerosis.
The study, called CAPTIVATE, took place between February 2004 and December 2005 and involved 40 clinics in the U.S., Canada, Europe, South Africa, and Israel.
Study participants randomly received a daily dose of either pactimibe or a placebo (dummy pill) in addition to standard cholesterol-lowering medications.
Researchers used ultrasound to measure the thickness of the wall of the carotid artery, a major blood vessel in the neck. Increasing thickness of the carotid artery is considered a sign of plaque buildup.
The study was stopped early after a follow-up of 15 months, when a similar trial (the ACTIVATE study) failed to show that pactimibe worked any better than a placebo.
After six months of treatment, those taking pactimibe had a significant increase in "bad" LDL cholesterol levels.
The pactimibe group had a 7.3% increase in LDL cholesterol, compared with 1.4% in the placebo group. Researchers noted the increase throughout the study and say that the levels dropped after the patients stopped taking the drug.
Carotid artery thickening also worsened in the pactimibe group within one year.
Serious cardiovascular events occurred more frequently among the patients taking pactimibe than those taking the placebo; 2.3% of the patients in the pactimibe group experienced a heart attack, stroke, or death, compared to 0.2% in the placebo group. More patients in the pactimibe group also required hospitalization for chest pain, stent placement, heart bypass surgery, or carotid surgery during the study period.
The CAPTIVATE study is the third in a series of trials to show that ACAT-1 inhibitors have no effect on atherosclerosis, according to background information in the journal article. The researchers conclude that all the findings taken together lessen "the promise and further development of this class of drugs for cardiovascular prevention."