Trial puts niacin—and cholesterol dogma—in the line of fire
Elie Dolgin
Nature Medicine 17, 756 (2011) doi:10.1038/nm0711-756
Published online 07 July 2011
The balance of 'good' and 'bad' cholesterol noted at routine checkups—and some of the drugs used to tip this balance—might not influence heart risk in the way widely thought.
It's already known that statins, which lower levels of low-density lipoprotein (LDL), do not work for everybody. As such, doctors have long sought to complement these agents that reduce 'bad' cholesterol with medicines such as niacins and fibrates that raise levels of the 'good' stuff—namely, high-density lipoprotein (HDL) cholesterol. New evidence, however, suggests that simply elevating HDL cholesterol levels in the blood does not necessarily translate into clinical benefit for patients.
“It's a beautiful hypothesis that HDL may be cardioprotective, and there are ample preclinical as well as observation data in support of that,” says Sanjay Kaul, a cardiologist at the Cedars-Sinai Medical Center in Los Angeles. “But when we put it to real test, which is the gold-standard randomized clinical trial, none of the treatments have passed muster.”
The most recent failure came in May when the US National Heart, Lung and Blood Institute (NHLBI) prematurely halted the AIM-HIGH study. The 3,400-person trial, which examined high-dose extended-release niacin given together with statin therapy, was cut short after a preliminary data analysis found no additional benefits of the vitamin B–based drug in this patient population. “Maybe we've been too simplistic in thinking that raising HDL any way confers the same benefit as when it happens physiologically, and that's what we're grappling with,” says the NHLBI's Patrice Desvigne-Nickens, a project officer for the trial.
“AIM-HIGH poses the most substantial challenge yet to the HDL cholesterol hypothesis,” says Dan Rader, a cardiologist at the University of Pennsylvania School of Medicine in Philadelphia who was not involved in the study. Michael Davidson, director of preventive cardiology at the University of Chicago and another trial onlooker, adds, “To those of us in the field, we thought it was the right kind of study—the right patient population to test the effect of niacin—and when the trial didn't work, it was both a disappointment and a surprise.”
Creative Commons
To B or not to B: Niacin questioned.
Adding to the uncertainty, on 19 May, a week before the NHLBI pulled the plug on AIM-HIGH, an advisory committee to the US Food and Drug Administration (FDA) came to a damning conclusion on another HDL-raising drug. Off the back of the recent ACCORD trial, which showed that a fibrate drug from Abbott Laboratories called TriCor (fenofibrate) provided no added benefit to that of statins in people with diabetes, the panel unanimously recommended that the Chicago company launch a new trial of a similar agent called Tripilix, the only fibrate medicine currently approved for use in combination with statins. Importantly, the panel said the trial should be based on clinical outcomes and not just changes in triglycerides or HDL cholesterol levels.
