More Bad News For HDL Therapies: ASSURE Trial Misses Primary Endpoint Reply

The string of bad news for HDL-related therapies continues. Resverlogix yesterday announced that the ASSURE clinical trial had failed to meet its primary endpoint. RVX-208, the drug being studied in the trial, is a novel small molecule that increases production of ApoA-1, which raises HDL levels and is thought to enhance reverse cholesterol transport.

Click here to read the full story on Forbes.

Steve Nissen

About these ads

WSJ Article Fails To Raise Key Questions About Cardiovascular Risk In Children Reply

There’s probably no greater public health issue than the long-term  consequences of the childhood obesity epidemic. So the Wall Street Journal should be commended for digging into some of the important science behind this problem in a feature article in today’s paper. The author, Ron Winslow, is widely regarded as the best working journalist who regularly covers cardiovascular medicine. But I’m afraid the article fails to raise several key questions about the topic and therefore misses an opportunity to educate people about its complexities.

The article deals with the “growing concerns about the cardiovascular health of millions of children in the U.S. who are considered obese or overweight” and then focuses on one recent study published in Pediatrics that “suggests there is a simple way to assess a child’s arterial health with a calculation based on an often-overlooked component of cholesterol: triglycerides.” Winslow faithfully reports the main finding of the study, which is that the triglyceride to HDL ratio corresponds closely with arterial stiffness. A stiff vessel is a sign of “accelerated aging” and “likely raises the risk of dangerous outcomes relatively early in adult life,” writes Winslow.

Winslow notes that an NHLBI panel now recommends universal cholesterol screening for children between 9 and 11, but there is no mention that some experts disagree with this recommendation.  Further, these screening tests focus on the measurement of LDL cholesterol. Winslow doesn’t discuss whether  LDL would be equally effective as triglycerides and HDL at identifying children with stiff arteries. Winslow writes, reasonably, that high triglycerides and low HDL “are a hallmark reflection of the poor diets and sedentary lifestyles that researchers say are behind the wide prevalence of obesity among both children and adults,” but there’s a big gap between that association and concrete recommendations to measure HDL and triglycerides in children and, more importantly, to take actions based on these measurements.

Click here to read the full story on Forbes.

scale_zero

HPS2-THRIVE: A ‘Disappointing But Clear’ Result Reply

The results of HPS2-THRIVE were “disappointing but clear,”  said Jane Armitage, who presented the results this morning at the ACC in San Francisco.

HPS2-THRIVE randomized 25,673 high-risk patients who could tolerate niacin to either placebo or extended-release niacin plus laropiprant (Tredaptive, Merck), an anti-flushing agent, in addition to background therapy. The primary endpoint was the time to first major vascular event, defined as the composite of non-fatal MI or coronary death, any stroke or any arterial revascularization.

Major vascular events occurred in 13.2% of the niacin arm and 13.7% of the placebo arm (p=0.29), despite causing average reductions in LDL of 10 mg.dL and triglycerides of 33 mg/dL, in addition to a 6 mg/dL increase in HDL. Armitrage reported that based on data from previous trials and observational studies, “it was anticipated such lipid differences might translate into a 10-15% reduction in vascular events.”

HPS2-THRIVE study chairman, Rory Collins, responded to a question in the press conference: “To the question is niacin dead? Well, it’s not healthy!”

Click here to read the full story on Forbes.

 

HPS2-THRIVE Coming Attraction: First Look At What Went Wrong With Niacin Reply

In a few weeks, on March 9, the main results of the HPS2-THRIVE (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) study will be presented in San Francisco at the annual meeting of the American College of Cardiology. These results have been eagerly awaited since Merck’s brief announcement in December that the trial had not met its primary endpoint and that it would no longer pursue approval of Tredaptive, the combination of extended-release niacin and laropiprant, in the US. The trial was designed to assess whether adding the niacin/laropiprant combination to standard statin therapy in high risk individuals would further reduce vascular events.

Now, serving almost as a coming attraction for the main event at the ACC, an important substudy from HPS2-THRIVE has been published in the European Heart JournalThe paper discusses the trial design, the pre-specified muscle and liver outcomes, and the reasons for stopping treatment during the trial.

Click here to read the full story in Forbes.

European Heart Journal

The Big Gamble of CETP Inhibitors 2

Merck has invested a substantial amount of money on the CETP inhibitor anacetrapib. Chemist and veteran pharma blogger Derek Lowe suspects that the company might as well have plunked the money down in a casino.

In a provocative new post, Lowe wonders if big pharma, in its desperation, has abandoned rational research in favor of, essentially, gambling. He notes that CETP is “a drug target that has incinerated a lot of money over the years” and wonders whether any of the compounds will “ever make it as a drug?” The failure of past CETP inhibitors, torcetrapib (Pfizer) and dalceptrapib (Roche), along with the recent failure of Tredaptive (Merck), “illustrate how little we know about this area [HDL].”

Read the rest of the post on Forbes.

 

Merck Starts To Suspend Worldwide Availability Of Tredaptive Reply

In the wake of the negative HPS2-THRIVE study announced last month, Merck said today that it was beginning to suspend the worldwide availability of Tredaptive, its combination of extended-release niacin and laropiprant.

Click here to read the full story on Forbes.

Should Niacin Still Be Prescribed? William Boden Versus Harlan Krumholz 1

In the wake of HPS2-THRIVE many have argued that there is no longer any reason to prescribe niacin. William Boden, the lead investigator of AIM-HIGH and COURAGE, thinks there were enough flaws in the design of the niacin trials to justify the cautious use of niacin in certain circumstances. Says Boden:

“There is evidence of clinical outcome improvement (i.e., CHD death/MI reduction) from VA-HIT for gemfibrozil; there is similar clinical outcome improvement for niacin from the Coronary Drug Project. Numerous studies show niacin’s benefit on surrogate outcome measures (i.e., quantitative coronary angiography, IVUS, cIMT, etc.). What more evidence do you need?”

” I have not given up on niacin.”

Harlan Krumholz  disagrees:

“We have to face the facts about the trials. They have failed to be supportive, and despite concerns about their flaws, they were developed by some of the best minds in our profession (including yours) and had millions of dollars devoted to them. I just feel that we cannot justify millions of people being prescribed a drug that has failed in two recent, large, prominent trials, which actually had signals of harm…”

Read the entire fascinating discussion over on CardioExchange.

Boden

William Boden

Harlan Krumholz

Harlan Krumholz