Featured Research

from universities, journals, and other organizations

Higher risks without cardio benefits halt study of aleglitazar

Date:
March 31, 2014
Source:
American College of Cardiology
Summary:
The phase III AleCardio trial was ended early when patients with type 2 diabetes and recent acute coronary syndrome who were treated with aleglitazar showed higher rates of heart failure, kidney events and gastrointestinal bleeding with no offsetting cardiovascular benefits, according to new data.

The phase III AleCardio trial was ended early when patients with type 2 diabetes and recent acute coronary syndrome who were treated with aleglitazar showed higher rates of heart failure, kidney events and gastrointestinal bleeding with no offsetting cardiovascular benefits, according to data presented at the American College of Cardiology's 63rd Annual Scientific Session. All other studies with the drug have been stopped as well.

Aleglitazar sparked interest for this patient population because of its dual action on two subtypes of the PPAR cellular receptors. PPAR gamma helps regulate glucose; PPAR alpha does the same for lipids -- fats and fat-like compounds in the blood that include cholesterol and triglycerides. Patients with type 2 diabetes were enrolled in AleCardio after hospitalization for acute coronary syndrome -- symptoms produced by a sudden blockage of blood flow to the heart -- and screening to make sure their condition was stable. Median time from onset of symptoms to enrollment was 28 days.

A total of 7,226 patients, average age 61, were randomly assigned to aleglitazar at 150 μg daily or placebo. Although the design called for continuing treatment until 7,000 patients had been followed for 2.5 years and 950 primary endpoint events had been evaluated, the trial was cut short at 522 events. Heart failure, bone fractures and reversible renal issues are known for this class of drug, but researchers failed to find the hoped-for countervailing benefit in the main efficacy endpoint: time to death from cardiovascular cause or first non-fatal heart attack or stroke.

"The only unprecedented adverse effect was gastrointestinal hemorrhage, and none of the safety signals were overwhelming," said Michael Lincoff, M.D., director of C5Research, the Cleveland Clinic Coordinating Center for Clinical Research in Cleveland. "The issue was futility of cardiovascular superiority, with primary efficacy endpoints reached for 9.5 percent of aleglitazar group compared with 10 percent of the placebo group."

Heart failure did not reach a level of significant difference for the aleglitazar group but showed a strong trend at 3.4 percent compared with 2.8 percent for placebo. The gastrointestinal hemorrhage rate for aleglitazar was higher at a statistically significant 2.4 percent compared to 1.7 percent for the placebo group. The rate of reversible kidney events was significantly higher at 7.4 percent for aleglitazar compared to 2.7 percent for the placebo group. Bone fracture rates for the two groups were not significantly different.

In general, the study found no differences in heightened risk by patient characteristics that would make it possible to direct the drug safely to a specific subgroup. Increases in "good" HDL cholesterol and decreases in triglycerides were seen, along with small increases in "bad" LDL cholesterol.

"This study highlights the difficulty in predicting cardiovascular outcomes based upon beneficial effects on metabolic endpoints, particularly in agents that affect a complex spectrum of pathways and especially multiple-gene activators such as this one," Lincoff said. "This study may well mark the end of this class of drug being tested clinically."


Story Source:

The above story is based on materials provided by American College of Cardiology. Note: Materials may be edited for content and length.


Cite This Page:

American College of Cardiology. "Higher risks without cardio benefits halt study of aleglitazar." ScienceDaily. ScienceDaily, 31 March 2014. <www.sciencedaily.com/releases/2014/03/140331100334.htm>.
American College of Cardiology. (2014, March 31). Higher risks without cardio benefits halt study of aleglitazar. ScienceDaily. Retrieved August 20, 2014 from www.sciencedaily.com/releases/2014/03/140331100334.htm
American College of Cardiology. "Higher risks without cardio benefits halt study of aleglitazar." ScienceDaily. www.sciencedaily.com/releases/2014/03/140331100334.htm (accessed August 20, 2014).

Share This




More Health & Medicine News

Wednesday, August 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola-Hit Sierra Leone's Freetown a City on Edge

Ebola-Hit Sierra Leone's Freetown a City on Edge

AFP (Aug. 19, 2014) Residents of Sierra Leone's capital voice their fears as the Ebola virus sweeps through west Africa. Duration: 00:56 Video provided by AFP
Powered by NewsLook.com
101-Year-Old Working Man Has All The Advice You Need

101-Year-Old Working Man Has All The Advice You Need

Newsy (Aug. 19, 2014) Herman Goldman has worked at the same lighting store for almost 75 years. Find out his secrets to a happy, productive life. Video provided by Newsy
Powered by NewsLook.com
Researcher Testing on-Field Concussion Scanners

Researcher Testing on-Field Concussion Scanners

AP (Aug. 19, 2014) Four Texas high school football programs are trying out an experimental system designed to diagnose concussions on the field. The technology is in response to growing concern over head trauma in America's most watched sport. (Aug. 19) Video provided by AP
Powered by NewsLook.com
American Ebola Patient Apparently Improving, Outbreak Is Not

American Ebola Patient Apparently Improving, Outbreak Is Not

Newsy (Aug. 19, 2014) Nancy Writebol, an American missionary who contracted Ebola, is apparently getting better, according to her husband. The outbreak, however, is not. 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