New drug bumps up good cholesterol

Anacetrapib lowers the bad stuff, too, new test indicates

CHICAGO — An experimental drug shows the ability to more than double a person’s good cholesterol score, potentially filling a huge gap in cardiovascular care, scientists report. If the findings hold up in a larger trial, the drug, called anacetrapib, stands poised to become the best medication yet for boosting levels of the heart-disease preventer HDL.

“This is a very exciting era we are entering,” said Christopher Cannon, a cardiologist at Harvard Medical School and Brigham and Women’s Hospital in Boston. He presented the findings at a meeting of the American Heart Association on November 17, the same day they appeared online in the New England Journal of Medicine.

“These preliminary data are very promising,” agreed Sidney Smith, a cardiologist at the University of North Carolina at Chapel Hill and a past president of the AHA. “They show dramatic differences in HDL.” High-density lipoprotein, or HDL, ushers low-density bad cholesterol, or LDL, out of the blood. High levels of HDL are closely associated with low risk of heart attack and stroke.

Cannon and his colleagues randomly assigned 1,623 people, average age 63, who had heart disease to receive either anacetrapib or a placebo for 18 months. All were already taking a statin drug to lower LDL. In the anacetrapib group, HDL levels shot up from an average of 41 milligrams per deciliter of blood to 101 mg/dl within the first few weeks of the study and stayed there. Anacetrapib also lowered LDL from an average of 81 mg/dl to around 45 mg/dl. People who received a placebo experienced very slight changes in their HDL and LDL scores.

Only eight people getting anacetrapib — compared with 28 in the placebo group, which was the same size — needed to undergo coronary revascularization during the trial, in which doctors surgically reopen or bypass a blocked artery to restore blood flow to the heart. “We’re very encouraged by this,” Cannon said.

“These were people who were doing fine” at the outset, despite having heart disease, Cannon says. The revascularization data indicate that in some of them, the heart disease was progressing despite being on medication.

But the data in this study are not enough to change medical guidelines, Smith cautioned, and Cannon agreed. Further work will be needed to establish that the higher HDL levels seen in patients taking anacetrapib are truly functional HDL, and that can be established only by a long-term reduction in heart attacks, stroke, angina and other tangible cardiac events. “If it does have a significant benefit on events, then we will have a very valuable potent new therapy to add,” Smith said.

Some people naturally have higher HDL than others. Apart from niacin, which has a side effect of flushed skin, no drug has previously been shown to safely increase HDL substantially. Stopping smoking, losing weight and exercising can add 5 to 10 points to a person’s HDL score, Smith said.

Anacetrapib works by inhibiting CETP, or cholesteryl ester transfer protein, a compound that influences how much LDL and HDL a person carries in the blood at any given moment. A promising drug called torcetrapib had shown the ability to neutralize CETP (SN: 5/1/04, p. 285). But research pitting the drug against a placebo was stopped in 2006 when it became clear that people taking torcetrapib were more likely to develop high blood pressure, experience heart problems or die than those getting a statin alone. The result was a blow to the drug’s maker, Pfizer, and left HDL-boosting drug hopes in limbo, although some work is ongoing (SN: 4/14/07, p. 237).

Anacetrapib has now shown “a very potent and impressive change in lipid profiles,” said Thomas Lüscher, a cardiologist at University Hospital Zurich. “And such change occurred without a change in blood pressure.” The number of deaths was roughly the same in the two groups.

But 142 people had their LDL drop so low on anacetrapib plus a statin that they were taken off the experimental drug as a precaution. Scientists will next test anacetrapib, manufactured by Merck, in a trial of 30,000 heart disease patients over four years, paying close attention to that risk and any other that arises, said cardiologist Rory Collins of the University of Oxford.

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