Featured Research

from universities, journals, and other organizations

New medication increases HDL cholesterol and decreases LDL cholesterol levels

Date:
November 16, 2011
Source:
JAMA and Archives Journals
Summary:
Among patients with sub-optimal low-density lipoprotein cholesterol (LDL-C) or high-density lipoprotein cholesterol (HDL-C) levels, use of the drug evacetrapib alone or in combination with statin medications was associated with significant increases in HDL-C levels and decreases in LDL-C levels, according to a new study.

Among patients with sub-optimal low-density lipoprotein cholesterol (LDL-C) or high-density lipoprotein cholesterol (HDL-C) levels, use of the drug evacetrapib alone or in combination with statin medications was associated with significant increases in HDL-C levels and decreases in LDL-C levels, according to a study appearing in the November 16 issue of JAMA, a theme issue on cardiovascular disease. The study is being released early online to coincide with its presentation at the American Heart Association Scientific Sessions.

Cardiovascular disease remains the leading cause of death. "Accordingly, considerable efforts have focused on development of novel therapeutic agents designed to address residual cardiovascular risk. Because individuals from the general population with elevations of HDL-C have a reduced incidence of coronary heart disease, it has been assumed that finding an appropriate therapy to increase HDL-C levels would yield substantial clinical benefit. However, development of drugs that increase HDL-C levels has been challenging and fraught with failures, including the premature termination of a large outcomes trial studying the effects of the cholesteryl ester transfer protein (CETP) inhibitor torcetrapib. Despite failure of the first drug in the class, considerable interest remains in CETP inhibition as a therapeutic strategy, by virtue of the ability of these agents to substantially increase HDL-C levels and, in some cases, reduce LDL-C levels," according to background information in the article. "Few studies have documented the efficacy and safety of CETP inhibitors in combination with commonly used statins."

Stephen J. Nicholls, M.B.B.S., Ph.D., of the Cleveland Clinic, and colleagues evaluated the biochemical efficacy, safety, and tolerability of the CETP inhibitor evacetrapib as monotherapy and in combination with statin agents commonly used in clinical practice in patients with dyslipidemia. The randomized controlled trial, which included 398 patients with elevated LDL-C or low HDL-C levels, was conducted from April 2010 to January 2011 at community and academic centers in the United States and Europe. Patients were randomly assigned to receive placebo (n=38); evacetrapib monotherapy, 30 mg/d (n=40), 100 mg/d (n=39), or 500 mg/d (n=42); or statin therapy (n=239) (simvastatin, 40 mg/d; atorvastatin, 20 mg/d; or rosuvastatin, 10 mg/d) with or without evacetrapib, 100 mg/d, for 12 weeks. The primary outcomes measured were percentage changes in HDL-C and LDL-C levels at the beginning of the trial to after 12 weeks of treatment. The average age of the participants was 58 years, and 56 percent were women.

The average lipid levels at the beginning of the study were 55.1 mg/dL for HDL-C and 144.3 mg/dL for LDL-C. The researchers found that as monotherapy, evacetrapib produced dose-dependent increases in HDL-C of 30.0 to 66.0 mg/dL (53.6 percent to 128.8 percent) compared with a decrease with placebo of -0.7 mg/dL (-3.0 percent) and decreases in LDL-C of -20.5 to -51.4 mg/dL (-13.6 percent to -35.9 percent) compared with an increase with placebo of 7.2 mg/dL (3.9 percent). The HDL-C changes were significantly greater among patients with lower levels of HDL-C or higher triglyceride levels at baseline.

When administered in combination with statin therapy, evacetrapib, 100 mg/d, increased HDL-C levels by 42.1 to 50.5 mg/dL (78.5 percent to 88.5 percent) and resulted in greater reductions in LDL-C (-67.1 to -75.8 mg/dL [-11.2 percent to -13.9 percent)] and non-HDL-C compared with effects observed with statin monotherapy. Compared with evacetrapib monotherapy, the combination of a statin and evacetrapib resulted in greater reductions in LDL-C but no greater increase in HDL-C, consistent with known lipid effects of statins.

There was no difference between evacetrapib and control groups in either the monotherapy or statin combination studies with regard to the rate of treatment-related adverse events and discontinuation rates.

"These preliminary findings suggest that evacetrapib could be administered with statins and may yield potentially clinically important incremental effects on lipoproteins," the authors write. "The results of the current study provide the foundation for a large phase 3 clinical trial designed to assess the efficacy and safety of evacetrapib."

Editorial: High-Density Lipoprotein Cholesterol as the Holy Grail

In an accompanying editorial, Christopher P. Cannon, M.D., of Brigham and Women's Hospital, Boston, comments on treatment strategies for low HDL-C levels.

"Current approaches to patients with low HDL-C levels are, first, institution of therapeutic lifestyle changes with diet and exercise and, if relevant, cessation of cigarette smoking. Each of these approaches has been shown to increase HDL-C and is associated with improved outcomes. The next step is to lower LDL-C. The current guidelines emphasize lowering LDL-C as the primary approach for patients with low HDL-C because it is a proven strategy, and the benefits of lowering LDL-C are present regardless of HDL-C levels (high or low). Next, in selected patients, some lipid experts use currently available therapies including niacin to increase HDL-C levels, although the evidence base for this approach is limited. Further interventions await data from the large randomized trials of current therapies (e.g., niacin) and emerging therapies like the CETP inhibitors, including dalcetrapib, anacetrapib, and, likely, evacetrapib. As such, the quest for the Holy Grail in coronary disease has many worthy knights on the trail."


Story Source:

The above story is based on materials provided by JAMA and Archives Journals. Note: Materials may be edited for content and length.


Journal References:

  1. Stephen J. Nicholls, H. Bryan Brewer, John J. P. Kastelein, Kathryn A. Krueger, Ming-Dauh Wang, Mingyuan Shao, Bo Hu, Ellen Mcerlean, Steven E. Nissen. Effects of the CETP Inhibitor Evacetrapib Administered as Monotherapy or in Combination With Statins on HDL and LDL Cholesterol: A Randomized Controlled Trial. JAMA, 2011; 306 (19): 2099-2109 DOI: 10.1001/jama.2011.1649
  2. Christopher P. Cannon. High-Density Lipoprotein Cholesterol as the Holy Grail. JAMA, 2011; 306 (19): 2153-2155 DOI: 10.1001/jama.2011.1687

Cite This Page:

JAMA and Archives Journals. "New medication increases HDL cholesterol and decreases LDL cholesterol levels." ScienceDaily. ScienceDaily, 16 November 2011. <www.sciencedaily.com/releases/2011/11/111115094610.htm>.
JAMA and Archives Journals. (2011, November 16). New medication increases HDL cholesterol and decreases LDL cholesterol levels. ScienceDaily. Retrieved July 25, 2014 from www.sciencedaily.com/releases/2011/11/111115094610.htm
JAMA and Archives Journals. "New medication increases HDL cholesterol and decreases LDL cholesterol levels." ScienceDaily. www.sciencedaily.com/releases/2011/11/111115094610.htm (accessed July 25, 2014).

Share This




More Health & Medicine News

Friday, July 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Beatings and Addiction: Pakistan Drug 'clinic' Tortures Patients

Beatings and Addiction: Pakistan Drug 'clinic' Tortures Patients

AFP (July 24, 2014) — A so-called drugs rehab 'clinic' is closed down in Pakistan after police find scores of ‘patients’ chained up alleging serial abuse. Duration 03:05 Video provided by AFP
Powered by NewsLook.com
Too Few Teens Receiving HPV Vaccination, CDC Says

Too Few Teens Receiving HPV Vaccination, CDC Says

Newsy (July 24, 2014) — The Centers for Disease Control and Prevention is blaming doctors for the low number of children being vaccinated for HPV. Video provided by Newsy
Powered by NewsLook.com
New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) — The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Newsy (July 24, 2014) — Sheik Umar Khan has treated many of the people infected in the Ebola outbreak, and now he's become one of them. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

    Health News

      Environment News

        Technology News



          Save/Print:
          Share:  

          Free Subscriptions


          Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

          Get Social & Mobile


          Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

          Have Feedback?


          Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
          Mobile iPhone Android Web
          Follow Facebook Twitter Google+
          Subscribe RSS Feeds Email Newsletters
          Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins