DEFINE: Anacetrapib raises HDL, lowers LDL
American Heart Association Scientific Sessions 2010
CHICAGO — The experimental cholesteryl ester transfer protein inhibitor anacetrapib was associated with marked increases in HDL levels and decreases in LDL levels without raising BP, according to new study results.
Researchers for the Determining the Efficacy and Tolerability of CETP Inhibition with Anacetrapib (DEFINE) trial enrolled 1,623 patients with known or prior CHD taking statins and randomly assigned in a double-blinded, 1:1 fashion to receive either 100 mg daily of anacetrapib (n=811; Merck) or placebo (n=812). The primary outcomes of interest were the percent changes from baseline in LDL at 24 weeks, with percent changes from baseline in HDL as a secondary endpoint.
According to the study results, LDL was reduced by 39.8% from 81 mg/dL to 45 mg/dL (P<.001) in patients taking anacetrapib vs. placebo. The researchers also reported a 138.1% increase in HDL levels in the anacetrapib group (from 41 mg/dL at baseline to 101 mg/dL at 24 weeks; P<.001). There were no reported changes in BP through 76 weeks, nor were changes in electrolyte or aldosterone levels reported.
Additionally, prespecified adjudicated CV events occurred in 16 patients in the anacetrapib group vs. 21 in the placebo group (P=.40). Torcetrapib, a previously evaluated cholesteryl ester transfer protein inhibitor, was associated with an increase in CV events, but the researchers suggested that the event distribution in DEFINE (via Bayesian analysis) yielded a predictive probability of 94% that anacetrapib would not be associated with a 25% increase in CV events seen with torcetrapib.
“We’re very encouraged with these results,” Christopher P. Cannon, MD, of Brigham and Women’s Hospital in Boston and senior investigator of the TIMI study group, said in a press conference. “This is a moderate-sized safety study, so we have reassurance that we can move forward and really test this [drug].”
Cannon announced the next step in testing anacetrapib – a study enrolling 30,000 patients with heart disease and a background of statin use. The study is scheduled to have 4-year follow-up.
The DEFINE study was funded by Merck Research Laboratories. – by Eric Raible and Stacey Fisher
For more information:
Cannon C. LBCT IV, Abstract 21824. Presented at: American Heart Association Scientific Sessions 2010; Nov. 13-17; Chicago.
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ASCOT: High-sensitivity CRP screening produced no significant improvements in CVD assessment
American Heart Association Scientific Sessions 2010
CHICAGO — High-sensitivity CRP was not found to be useful in improving risk factor prediction of CV outcomes in patients with hypertension, according to late-breaking clinical trial data.
The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) included 9,098 adults with hypertension who were randomly assigned to either calcium channel blocker or beta blocker treatment. Further, 4,853 patients who had <6.5 mmol/L total cholesterol were randomized to atorvastatin (Lipitor, Pfizer) or placebo.
At six months, researchers found that atorvastatin reduced LDL cholesterol by 40.3% and median high-sensitivity CRP (hsCRP) by 27.4%. Among those assigned to atorvastatin, LDL cholesterol lower than the median (2.1 mmol/L) correlated with a significant reduction in CV events vs. patients with LDL at or above the median.
Conversely, hsCRP levels in patients assigned to atorvastatin were not associated with CV events (OR=0.86; 95% CI, 0.49-1.51) when researchers compared patients with less than the median hsCRP (1.83 mg/L) to those having at least the median hsCRP.
At a press conference, Peter Sever, FRCP, professor of clinical pharmacology and therapeutics, Imperial College London and study investigator, said of the study, “neither baseline nor on-treatment CRP provide any useful information about the efficacy of statin treatment to reduce CV events beyond LDL cholesterol reduction. These results do not support current proposals to measure CRP in the clinical setting either to assign statins to individuals on the basis of an elevated CRP alone or to monitor CRP levels as an indicator of the efficacy of statin treatment.” – by Brian Ellis
For more information:
Sever PS. LBCTIV, Abstract#21685. Presented at: American Heart Association Scientific Sessions 2010; Nov. 13-17; Chicago.
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