By Elie Dolgin

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.

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