A large randomized trial of high-dose extended-release niacin in heart disease patients who have well-controlled low-density lipoprotein (LDL) cholesterol but low high-density lipoprotein (HDL) cholesterol and high triglyceride levels has been stopped 18 months early, mainly because the treatment failed to reduce cardiovascular events.

The move by the National Heart, Lung, and Blood Institute (NHLBI) came after a meeting of the trial’s Data Safety and Monitoring Board on April 25, 2011 determined that over 32 months of follow-up there were no significant differences in cardiovascular event rates between patients who, in combination with statin treatment, did or did not receive high-dose niacin. A higher rate of ischemic stroke among niacin patients also contributed to the decision to halt the trial, according to a National Institutes of Health (NIH) press release.

The AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health) trial randomized 3,414 at-risk patients (most with CAD) to high-dose, extended-release niacin (Niaspan, Abbott Laboratories, Abbott Park, IL) in gradually increasing doses up to 2,000 mg/day (n = 1,718) or a placebo (n = 1,696). In addition, all participants were prescribed simvastatin, and 515 also received ezetimibe, to keep their LDL levels within a target range of 40-80 mg/dL.

“The lack of effect on cardiovascular events is unexpected and a striking contrast to the results of previous trials and observational studies,” said co-principal investigator Jeffrey Probstfield, MD, of the University of Washington (Seattle, WA), in the NIH press release.

According to the press release, the small excess number of strokes—28 (1.6%) in the niacin group vs. 12 (0.7%) in the placebo group—was unexplained and may have been due to chance. Previous studies have not suggested stroke as a possible niacin complication. In addition, it was noted that 9 of the 28 strokes in the niacin group occurred in subjects who had discontinued the drug between 2 months and 4 years before their stroke.

Study participants have been informed of the results and will be scheduled for clinic visits within the next 2.5 months, according to the press release. Participants will be followed for an additional 12 to 18 months.

Results Not Applicable in Higher-Risk Population

Meanwhile, the other co-principal investigator, William E. Boden, MD, of Buffalo General Hospital (Buffalo, NY), cautioned in the NIH release, “The results from AIM-HIGH should not be extrapolated to apply to potentially higher-risk patients such as those with acute heart attack or acute coronary syndromes, or in patients whose LDL cholesterol is not as well controlled as those in AIM-HIGH.”

In a separate statement, the US Food and Drug Administration (FDA) said, “At this time FDA has made no new conclusions or recommendations regarding the use of extended-release niacin alone or in combination with simvastatin or other statins.” The agency announced plans to conduct a comprehensive review of the AIM-HIGH trial data to determine their impact on the approved indications for extended-release niacin.

According to the NIH press release, several other trials testing the impact of raising HDL levels in patients at risk of cardiovascular events, including use of high-dose niacin, are ongoing.

2. US Food and Drug Administration. FDA Statement on the AIM-HIGH Trial. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm256841.htm. Accessed May 27, 2011. Published May 26, 2011.

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