New Drug May Safely Boost 'Good' Cholesterol
Anacetrapib Doubles HDL, Lowers LDL, While Hitting Safety Goals
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.