December 2, 2011
Niacin Much Less Helpful in the Age of Statins
Niacin has been getting some bad press recently. A brief retrospective of Niacin’s rise to prominence will help us understand its recent fall from favor.
Niacin is also known as vitamin B3 or nicotinic acid, a molecule that we need in tiny quantities in our food. As far back as the 1950s it was known that niacin in higher doses reduces blood levels of cholesterol. At that time our understanding of heart disease was in its infancy and there were few effective medications to treat or prevent cardiovascular disease.
From 1966 to 1969 a trial called the Coronary Drug Project (CDP) was conducted that would prove to be niacin’s finest hour. The CDP enrolled patients who had suffered a prior heart attack and randomized them to placebo or niacin. My understanding of those years suggests that all the patients wore paisley shirts, had very long hair, rioted outside political conventions, and landed on the moon. The trial showed a reduction in strokes and heart attacks of about 25% in the patients receiving niacin. The CDP findings from over 40 years ago are the strongest suggestion we have that niacin helps prevent cardiovascular disease. The important thing to remember about the CDP is that many of the medications that are now used routinely in patients with heart disease, like aspirin and certain blood pressure medicines (beta blockers) were used rarely then. But that’s not surprising. After all, back then we thought that polka dots and hair were attractive in any quantity. Can you dig it?
Fast forward twenty years. The paisley and polka dots were replaced by skinny ties and Ray-Bans. The first statin, lovastatin (Mevacor), appeared on the market in 1987. My regular readers know that statins are a family of cholesterol-lowering medications which have been extensively proven to prevent strokes and heart attacks. Statins are also the most potent reducers of LDL, the cholesterol molecule most linked to stroke and heart attack risk. Meanwhile, other medications like aspirin and beta-blockers were proven to extend life and prevent heart attacks in people with prior heart attacks. The management of heart disease was progressing by leaps and bounds, and mortality from heart disease has been decreasing ever since.
So statins rapidly overshadowed niacin for management of cholesterol, and for good reasons. Niacin has side effects that are more difficult to tolerate, it lowers cholesterol less, and the evidence of its ability to prevent strokes and heart attacks is largely from one study – the CDP. Nevertheless, niacin has continued to be prescribed, largely because it has one benefit that statins don’t have. Niacin elevates the levels of HDL, a cholesterol molecule that is associated with lower heart attack and stroke risk.
This year a large trial called AIM-HIGH attempted to answer whether niacin taken with a statin is superior to a statin alone in patients with cardiovascular disease and low HDL. I wrote about the AIM-HIGH study in May when it was completed but before the full results were published. The full results were finally published two weeks ago. (You may want to read my May post for details about the study and for a more detailed explanation of LDL and HDL.)
The study enrolled patients with known cardiovascular disease with low HDL and randomized them to two groups. One group received a statin (simvastatin, sold under the brand Zocor) and niacin. The second group received simvastatin and a placebo. The niacin group had lower LDLs, higher HDLs, and lower triglycerides than the placebo group. But surprisingly there was no difference between groups in the rate of strokes and heart attacks.
What does this mean? Why didn’t better cholesterol numbers translate to better outcomes?
The first possible explanation (which I offered in May) is that low HDL is simply a marker of heart attack risk, not a cause. This is the same reason that putting an ice cube on your thermometer on a very hot day won’t make you feel more comfortable, since the thermometer reading is a marker for your discomfort, not a cause. Another explanation is that niacin alone does have some benefit (as shown in the CDP) but that the benefit of more modern medications is much greater. And that in the presence of statins and aspirin and other proven medications, niacin may not offer any additional advantage. Both explanations may be true.
So we’re likely seeing the waning days of niacin use. It may remain a reasonable option for patients who can’t tolerate statins. For the majority of patients who can tolerate statins, niacin has no value.
Important legal mumbo jumbo: