In 2011, federal health officials ended an important government-funded clinical trial designed to test whether taking niacin in addition to a cholesterol-lowering statin might do more to lower heart attack and stroke risk than just taking a statin alone. Interim data indicated that the niacin had no benefit and may have been associated with a small, unexplained increase in stroke risk.
Full results of the AIM-HIGH trial, as it was called, were published several months later in The New England Journal of Medicine. Experts continue to fight over the AIM-HIGH results in that ferocious way that experts often do. Some say the results are strong evidence for not adding niacin to statin therapy. Others are adamant that AIM-HIGH missed the mark because of the way it was designed and that it will take the results of a different trial, dubbed THRIVE, to determine if niacin-statin combinations have cardiovascular benefits.
Another name for niacin is vitamin B3, and we need small amounts of it — about 15 milligrams a day — to prevent a nutritional deficiency disease called pellagra (a major public health problem in the American South in the early 20th century). But niacin in large amounts — about 2,000 mg a day — was also found to have an effect on cholesterol levels, tamping down “bad” LDL cholesterol some and increasing “good” HDL by quite a lot. It also modestly reduces elevated triglyceride levels, which are associated with heart disease.
When the results don’t add up: The AIM-HIGH trial
The notion of adding niacin to statins came about for several reasons. Statins do a terrific job of cranking down LDL levels, but they’re not big HDL boosters. Studies have shown that increasing HDL while taking a statin might lower cardiovascular risk further. And pharmaceutical companies are looking for new products, especially now that the patents on their brand-name statins, like Lipitor (atorvastatin), have expired.
Everyone in the AIM-HIGH trial took a statin to get their LDL levels down to a very low level (40 to 80 mg/dL). Half were randomly assigned to take 1,500 to 2,000 mg of extended-release niacin a day. The other half received a placebo.
What’s interesting about the AIM-HIGH results is that the extended-release niacin did what it’s supposed to do: it increased HDL levels and lowered triglycerides. But over a three-year period, those changes didn’t translate into fewer heart attacks, strokes, or other cardiovascular events.
So one moral of this story is HDL levels and triglycerides can be overprized. They’re just biomarkers. It’s the effect they have on cardiovascular disease that matters. Some other statin-plus-HDL-booster combinations, notably a drug called torcetrapib, have exhibited a similar disconnect between increasing HDL and so-called clinical events.
But don’t write off niacin just yet. It was called the AIM-HIGH trial but the LDL targets in the trial were very low. Adding niacin to a statin might benefit those with more middling sorts of LDL levels. And the THRIVE results may add another twist to an already complicated tale.