Hartford, CT - The US National Institutes of Health (NIH) is to sponsor a new trial to evaluate the merits of simultaneously lowering LDL and raising HDL.

The trial, known as Atherothrombosis Intervention in Metabolic Syndrome with Low HDL-C/High Triglyceride and Impact on Global Health Outcomes (AIM-HIGH), will compare the incidence of major cardiovascular events in patients randomized to extended-release niacin (Niaspan, Kos Pharmaceuticals) plus simvastatin (Zocor, Merck) or simvastatin alone. Expected to start this October and run for six years, the study plans to enroll 3300 patients with established vascular disease.

The trial is being run by Drs William Boden (Hartford Hospital, CT) and Greg Brown (University of Washington School of Medicine, Seattle). Boden told heartwire that the trial is estimated to cost about $42 million, of which the NIH is contributing $22 million, the remainder being provided by Kos.

Boden said the NIH obviously believes this is an important area, as the funding was approved at the first application. "To get NIH funding first time through is remarkable and speaks volumes," he commented.

The announcement of NIH funding for this trial follows soon after the decision by Pfizer to test and market its new HDL-raising drug, torcetrapib, only as a combination product with atorvastatin (Lipitor), which has sparked criticism of both the company and the FDA for allowing such a move.

Boden said he did not know whether the NIH funding of the Niaspan trial was linked to Pfizer's decision. "It may be part of the reason they funded our trial, but they obviously appreciate the importance of investigating different methods of raising HDL," he remarked.

He pointed out that although torcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, does raise HDL effectively, there is some doubt about whether CETP inhibition will actually result in a lowering of cardiovascular events. "It may not turn out to be the best method, so it is vital to investigate other approaches as well."

He pointed out that a third HDL-raising trial was also under way—the ACCORD trial, which is testing fenofibrate plus a statin vs a statin alone in type 2 diabetics.

Niacin has been known to raise HDL for many years but has not been widely used, as it has tolerability issues—mainly flushing. But these are reduced with the new extended-release formulation.

Boden explained that the AIM-HIGH trial has been designed to exclude patients who will not be able to tolerate Niaspan, so that most patients should be able to remain on the drug throughout the trial. Before randomization, all patients will undergo a four-week open-label period on Niaspan, which will be uptitrated from 500 mg to 2 g. Those who tolerate this well will go on to enter the main trial and be assigned to either Niaspan plus simvastatin (40 mg) or simvastatin 80 mg alone. To be eligible for enrollment, patients must have low HDL (<40 mg/dL for men and <50 mg/dL for women) and high triglycerides (>150 mg/dL). Boden estimates that about 50% to 60% of CHD patients would fit this profile.

He noted that the decision was made to use simvastatin as the statin in this trial because it was coming off patent in 2006 in the US, which would allow Kos to develop a niacin/simvastatin combination product. But he added that Niaspan will remain available for use with any statin.