Treatment Phase of Study Stopped
The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health has stopped the blinded treatment phase of the AIM-HIGH Clinical Trial 18 months earlier than planned. AIM-HIGH was designed to test whether raising HDL and lowering triglycerides in people with heart and vascular disease and well controlled LDL levels would reduce the risk of repeat heart and vascular problems. Half of the study participants took high dose, extended release niacin plus a statin drug and the other half took a statin drug only. Interim results of the study concluded that there was no difference between the two treatment groups.
Reason for Stopping the Blinded Treatment Phase of AIM-HIGH
As is usual in clinical trials, the NHLBI set up an independent data and safety monitoring board (DSMB) to monitor trial progress and participant safety. At a regularly scheduled meeting on April 25, 2011, the AIM-HIGH DSMB concluded that high dose, extended-release niacin offered no benefits beyond statin therapy alone in reducing cardiovascular-related complications in this trial. The rate of clinical events was the same in both treatment groups, and there was no evidence that this would change by continuing the trial. For this reason, the DSMB recommended that the NHLBI end the blinded treatment phase of the study.
The DSMB also noted a small and unexplained increase in ischemic stroke rates in the high dose, extended-release niacin group. This contributed to the NHLBI acting director's decision to stop the blinded treatment phase of the trial before its planned conclusion. During the follow-up period, there were 28 strokes (1.6 percent) reported among participants taking high dose, extended-release niacin versus 12 strokes (0.7 percent) reported in the control group. Nine of the twenty-eight strokes in the niacin group occurred in participants who had discontinued the drug at least two months and up to four years before their stroke. Previous studies do not suggest that stroke is a potential complication of niacin, and it is not clear whether this trend in AIM-HIGH arose by chance, was related to taking niacin, or some other issue.
The NHLBI has recommended that researchers continue to follow all participants for 12-18 months after the study medication is stopped to collect additional safety data.
Data collection and analysis will continue and the preliminary outcomes of the study are expected to be reported at the American Heart Association meetings in the fall of 2011.
AIM-HIGH Study Design and Criteria for Participation
AIM-HIGH tested whether adding high dose, extended-release niacin to a statin (simvastatin) was safe and more effective than a statin alone in reducing repeat cardiovascular events.
Ninety-four sites in the United States and Canada enrolled 3,414 participants between January 2006 and May 2010. Follow-up was scheduled to finish in 2012.
All study participants were at least 45 years old and had:
- A history of cardiovascular disease
- Low levels of HDL or "good" cholesterol
- High levels of triglycerides, another type of fat in the blood
Many participants also had diabetes or metabolic syndrome, a combination of risk factors for heart disease.
The study examined whether the combination statin/niacin therapy was safe and whether it lowered the risk of total heart or vascular events including:
- Coronary heart disease death
- Non-fatal heart attack
- Ischemic stroke (when arteries leading to the brain are blocked)
- Hospital stays for acute coronary syndrome (chest pain related to heart problems or angina)
- Coronary or cerebral revascularizations (procedures to improve blood flow in the vessels of the heart or brain)
Participants were assigned by equal chance to one of two groups. One group received high dose, extended-release niacin (Niaspan ®) while the other received a placebo (an inactive substance). Neither the participant nor the provider knew who was getting the active study drug or a placebo. The niacin dose was up to 2,000 mg per day, depending on the highest dosage a participant could tolerate during the trial's starting phase. \
All participants received the statin drug simvastatin (Zocor ®). The simvastatin dose was adjusted to keep LDL levels within a target range of 40-80 mg/dL (1.0-2.1 mmol/L). Some participants also received ezetimibe (Zetia ®), another cholesterol-lowering drug, to help reach the target LDL range.
Participants in AIM-HIGH were to be followed for 4-6 years on study medication. The blinded treatment phase of the study was stopped 18 months early. The average follow-up on study medication was 32 months.
For more information, please see the NHLBI press release