The NIH opted to halt the Atherothrombosis Intervention in Metabolic Syndrome with Low HDL Cholesterol and High Triglyceride and Impact on Global Health Outcomes Study, also known as the AIM-HIGH trial on niacin.
With news of the early dismissal of the latest trial on niacin therapy for cholesterol and cardiovascular disease, some are just closing the book on niacin.
As an avid supporter of the health benefits of vitamins, especially vitamin B3, I am compelled to delve deeper into this potentially trend-setting study.
In uncovering the design of the trial, the most glaring flaw, in my opinion, was the selection of the subjects for both groups. The treatment group was given Niaspan, a high dose extended release form of niacin, along with Simvastatin, a cholesterol lowering statin medication.
On the other hand, the so called placebo group was also given Simvastatin. Not a true placebo, clearly the statin-free niacin group was missing from this trial.
To further complicate things, 515 of the nearly 3,500 subjects got another cholesterol modifying drug, Ezetimibe.
Dosages of the various medications fluxuated in order to maintain the LDL cholesterol target range at 40-80mg/dl.
It was the Data and Safety Monitoring Board (DSMB) who decided to stop the trial based on their conclusion 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 this would change by continuing the trial.” [1]
I can understand stopping a trial early when the evidence of harm from one group over another is so obvious that it would be unethical to continue, but stopping early with no evidence of harm doesn’t really make sense. The AIM-HIGH trial was supposed to be five years long, but closed 18 months early.
Dr. William E. Boden (Buffalo General Hospital, NY) said that the extended release niacin did alter lipids in a predictable fashion by “increasing HDL levels by 20% and reducing triglycerides by around 25%”[1 ].
Despite these positive changes on the cholesterol surrogate markers, there seemed to be no effect on the incidence of cardiovascular events in the two groups who were all already on statin therapy.
While it was suggested that there might be a slightly higher incidence of ischemic stroke in one group, this has been dismissed by Dr. Daniel Radner (University of Pennsylvania, Philadelphia). He “does not believe the difference in ischemic stroke between the arms in the trial was real. There was no compelling evidence of harm” [1 ].
Does this mean that Niacin is useless?
Some may wish to interpret this one study that way. Certainly statin proponents may prefer not to have the completion.
Does this mean that the HDL hypothesis is invalid? The confusing battle between good and bad cholesterol will continue. Evidence is mounting that suggest that surrogate markers like cholesterol are not direct indicators of cardiovascular disease risk. If only it could be that easy.
Dr. Tara Macart owns Opti-Balance Naturopathic Medicine in Qualicum Beach with her husband Jonathan.
References: [1] Nainggolan, Lisa: “NIH pulls plug on AIM-HIGH trial with niacin.” Bethesda, MD, Theheart.org (May 27, 2011).