Study finds no benefit over placebo in ASSURE trial

September 3, 2013, Cleveland Clinic

Patients with coronary artery disease and low levels of "good cholesterol – or high-density lipoprotein (HDL) – who were treated with a drug designed to increase HDL levels and reduce coronary plaque build-up, experienced no better results than those treated with placebo, according to research conducted by the Cleveland Clinic Coordinating Center for Clinical Research (C5Research).

The drug, RVX-208, induces the production of apolipoprotein A1 (apoA1), a major protein in HDL. Prior research has shown that higher levels of HDL are associated with improved coronary health, so the ASSURE trial was designed to test whether increased production of apoA1 with the drug RVX-208 would raise HDL levels and slow the progression of coronary atherosclerosis, or plaque build-up in the coronary arteries.

The results of the ASSURE (ApoA1 Synthesis Stimulation and Intravascular Ultrasound for Coronary Atheroma Regression Evaluation) trial were presented at the European Society of Cardiology Congress 2013. ASSURE was a prospective, randomized, multicenter, double-blind clinical trial.

A team of researchers led by Stephen J. Nicholls, M.D., Ph.D., senior consultant to Cleveland Clinic's C5Research and Professor of Cardiology and Deputy Director at the South Australian Health & Medical Research Institute (SAHMRI) in Adelaide, Australia, used intravascular ultrasonography (IVUS) to assess the degree of coronary disease in study subjects at baseline and after 26 weeks on oral RVX-208 or placebo. IVUS is a medical imaging technology in which a small ultrasound probe is inserted via a catheter into an artery, allowing physicians to examine the inside of arteries via sonogram. The researchers also took baseline and 26-week measurements of apoA1 and HDL.

The primary endpoint – the change in percent atheroma volume (PAV), or the amount of artery volume taken up by disease – was not met. The PAV decreased by 0.4 percent in the RVX-208 group and 0.3 percent in the placebo group. Secondary IVUS endpoints – the change in total atheroma volume (TAV), or size of the disease, and the change in atheroma volume in the most severely diseased portion of the artery – also did not differ substantially between the RVX-208 group and the placebo group. Further, the biochemical endpoints of increased aopA1 and HDL levels, and decreased LDL, or bad cholesterol levels, also failed compared to placebo.

"Our results show that RVX-208 treatment did not result in any measurable incremental benefit on plaque regression for patients with coronary artery disease and low HDL ," said Nicholls. "The findings could reflect either a lack of efficacy of RVX-208, or the general inability to improve on the benefits produced by statins and other cardiovascular therapies."

All of the patients in ASSURE were being treated with atorvastatin or rosuvastatin, drugs shown in clinical trials to lower LDL levels.

"Ever since statins were approved more than 25 years ago, there has been an intensive, concerted effort in the scientific community to find an HDL-raising drug that will work in tandem with statins and improve cardiovascular outcomes," said Steven Nissen, M.D., Chairman of the ASSURE trial and Chairman of the Robert and Suzanne Tomsich Department of Cardiovascular Medicine at Cleveland Clinic. "Unfortunately, that search must go on."

Explore further: ASSURE study of experimental agent to raise HDL yields 'disappointing and surprising' results

Related Stories

ASSURE study of experimental agent to raise HDL yields 'disappointing and surprising' results

September 2, 2013
The search continues for an agent that increases high-density lipoprotein (HDL) and reduces arterial plaque, after the experimental apolipoprotein A1 (apoA1) inducer, RVX-208 failed to do so in the ApoA1 Synthesis Stimulation ...

Hot Line IV: Late-breaking trials on heart failure and acute coronary syndrome

September 3, 2013
The blood pressure lowering drug aliskiren did not improve coronary artery disease when given to patients who had prehypertension, results of the Aliskiren Quantitative Atherosclerosis Regression Intravascular Ultrasound ...

Two statin drugs similarly effective in reversing coronary heart disease

November 15, 2011
Maximum doses of Crestor (rosuvastatin) or Lipitor (atorvastatin) are similarly effective in reversing the buildup of cholesterol plaques in the coronary artery walls (atherosclerosis) after 24 months of treatment, according ...

Niacin added to statin therapy increases HDL cholesterol levels but does not improve HDL functionality, research shows

March 12, 2013
While two large clinical trials recently showed that adding niacin to statin therapy failed to improve clinical outcomes despite a significant increase in HDL-C levels, little is known about exactly why the increased HDL-C ...

Statins reduce CV events in CAD patients with very low LDL-C

September 1, 2013
Aggressive treatment with statins reduces the risk of subsequent cardiovascular events in patients with coronary artery disease even if they have very low LDL cholesterol levels, reveals research presented at ESC Congress ...

Recommended for you

A nanoparticle inhalant for treating heart disease

January 18, 2018
A team of researchers from Italy and Germany has developed a nanoparticle inhalant for treating people suffering from heart disease. In their paper published in the journal Science Translational Medicine, the group describes ...

Starting periods before age of 12 linked to heightened risk of heart disease and stroke

January 15, 2018
Starting periods early—before the age of 12—is linked to a heightened risk of heart disease and stroke in later life, suggests an analysis of data from the UK Biobank study, published online in the journal Heart.

'Decorated' stem cells could offer targeted heart repair

January 10, 2018
Although cardiac stem cell therapy is a promising treatment for heart attack patients, directing the cells to the site of an injury - and getting them to stay there - remains challenging. In a new pilot study using an animal ...

Two simple tests could help to pinpoint cause of stroke

January 10, 2018
Detecting the cause of the deadliest form of stroke could be improved by a simple blood test added alongside a routine brain scan, research suggests.

Exercise is good for the heart, high blood pressure is bad—researchers find out why

January 10, 2018
When the heart is put under stress during exercise, it is considered healthy. Yet stress due to high blood pressure is bad for the heart. Why? And is this always the case? Researchers of the German Centre for Cardiovascular ...

Heart-muscle patches made with human cells improve heart attack recovery

January 10, 2018
Large, human cardiac-muscle patches created in the lab have been tested, for the first time, on large animals in a heart attack model. This clinically relevant approach showed that the patches significantly improved recovery ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.