August 30, 2016
From Our 2010 Archives
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New Drug May Safely Boost 'Good' Cholesterol

Anacetrapib Doubles HDL, Lowers LDL, While Hitting Safety Goals

By Charlene Laino
WebMD Health News

Reviewed By Laura J. Martin, MD

Nov. 17, 2010 (Chicago) -- An experimental pill that boosts levels of "good" HDL cholesterol has cleared a major safety hurdle, renewing hopes of fighting heart disease in a new way.

Although the study of the drug, anacetrapib, was designed to look primarily at its safety, researchers say they were stunned by its dramatic effects on cholesterol levels.

"Our jaws dropped when we saw the 138% increase in HDL [over placebo]. And our jaws dropped even more when LDL went down by 40%," compared with placebo, says study leader Christopher P. Cannon, MD, of Brigham and Women's Hospital in Boston.

"This is an unprecedented change" in HDL levels, he tells WebMD.

The 18-month study enrolled more than 1,600 heart disease patients who were on statin drugs.

Importantly, anacetrapib did not appear to raise the risk of heart attacks or death from heart disease, major complications that halted development of its cousin torcetrapib, Cannon says.

Larger Study of HDL Booster Planned

Nevertheless, as studies of torcetrapib show, improving HDL cholesterol does not necessarily translate into better outcomes.

No firm conclusions about anacetrapib's effectiveness in fighting heart disease can be drawn until results of a 30,000-patient trial set to start next year are in -- and that could take up to four years, doctors say.

The new findings were reported here at the American Heart Association's (AHA) Scientific Sessions 2010 and simultaneously published online by the New England Journal of Medicine.

Other doctors here were also encouraged by the results, but reiterated that these are still the early days.

AHA spokesman Robert Eckel, MD of the University of Colorado in Denver tells WebMD, "These are magnificent results. The HDL effect is dramatic and the LDL effect is greater than we thought it would be."

Although the trial focused on safety, "there was a strong signal" of effectiveness as well, says Eckel, who was not involved with the study.

"However, we have to await the results of the outcomes trial," he says.

Statins Don't Help Everyone: Enter HDL Boosters

Although credited with making a substantial dent in heart disease, statin drugs that lower LDL cholesterol don't help everyone: Some statin users have heart attacks anyway.

That's why the search is on for drugs that boost levels of HDL cholesterol, which is thought to ferry cholesterol from the bloodstream to the liver, where it can be reprocessed.

Like its predecessor torcetrapib, anacetrapib blocks an enzyme called CETP that is responsible for transforming good cholesterol into bad cholesterol. If you inhibit this enzyme, HDL goes up and LDL goes down.

"There was a big black cloud when torcetrapib increased deaths and cardiovascular disease," Cannon says.

Doctors told WebMD at the time that the failure doesn't necessarily rule out the possibility that another drug in the class, with no evidence of toxicity, could possibly work.

And at least in this research, that appears to be the case.

Another CETP blocker called dalcetrapib is already in late-stage phase III testing, although studies to date suggest it does not appear to have the same impact on cholesterol as anacetrapib.

Anacetrapib Boosts HDL, Lowers LDL

The new study involved 1,623 patients with or at high risk for coronary heart disease and whose LDL was in the recommended range of 50 and 100 milligrams per deciliter (mg/dL) on statin therapy. They were given either anacetrapib or placebo daily for 18 months.

HDL cholesterol levels more than doubled by 24 weeks in those given anacetrapib, shooting up from an average of 41 mg/dL to 101 mg/dL. In contrast, they trickled up in the placebo group, from 40 mg/dL to 46 mg/dL.

Among patients on anacetrapib, LDL levels dropped from an average of 81 mg/dL to 45 mg/dL. Among the placebo group, LDL levels only declined from 82 mg/dL to 77 mg/dL.

There were no changes in blood pressure or aldosterone levels -- problems that plagued torcetrapib -- compared with placebo. Aldosterone is a hormone produced in the adrenal gland that affects kidney function and blood pressure.

Although the study wasn't long enough or large enough to look at anacetrapib's effect on cardiovascular events, statistical analysis that "compares what we have to what we know gave us 94% confidence" that it would not increase the risk of heart attacks, deaths from cardiovascular disease, strokes, or hospitalizations for unstable angina, he says.

Anacetrapib Cuts Need for Heart Procedures

Of note, Cannon says, is that substantially fewer people on the new drug needed to undergo bypass surgery or angioplasty to open up blocked arteries: 8 vs. 28 in the placebo group.

Although the numbers are small, the two-thirds reduction in such procedures is a hint that over time, the drug will decrease cardiovascular events, he says.

In the study, people were taken off anacetrapib if their LDL levels dropped below 25 mg/dL; this occurred in 142 (17%) of patients. "We don't know [if lowering LDL to such low levels will cause harm], so we played it safe," Cannon says.

Participants were about 63 years old on average; 23% were women; 17% were Asian, African-American or multiracial, and 15% were Hispanic. Just over half already had heart disease or had suffered a heart attack; the rest were at risk for heart disease.

The study was funded by Merck Research Laboratories, maker of anacetrapib.


American Heart Association's Scientific Sessions 2010, Chicago, Nov. 13-17, 2010.

Christopher P. Cannon, MD, cardiovascular division, Brigham and Women's Hospital, Boston.

Robert Eckel, MD, professor of medicine, physiology & biophysics, University of Colorado, Denver.

Cannon, C. New England Journal of Medicine, published online Nov. 17, 2010.

© 2010 WebMD, LLC. All rights reserved.

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