In late 2012, news arrived that a large study, which paired extended-release niacin with a statin, had been shut down prematurely. This study, known as HPS2-THRIVE (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events), is the largest trial of niacin's heart benefits ever conducted, involving 25,673 subjects between ages 50 and 80 in Europe and Asia at high risk for heart attacks or strokes.
However, HPS2-THRIVE had a twist: In addition to simvastatin (and ezetimibe, as needed), half the participants took a medication called Tredaptive, which is a combination of extended-release niacin and laropiprant, a drug that's supposed to minimize niacin flush. The other half of the participants took placebos.
In December 2012, Merckthe maker of all three drugs used in the trial and the sponsor of HPS2-THRIVEannounced that the study was being halted early. The reason: Taking Tredaptive didn't appear to offer any additional protection against heart attacks or strokes but might increase the risk for certain side effects. Most notably, Tredaptive users were more likely to develop myopathy, or muscle weakness and pain, a known side effect of simvastatin and other statins.
When compared with patients taking simvastatin and a placebo, the HPS2-THRIVE subjects who used Tredaptive were four times more likely to report muscle problems. Past studies have also suggested that niacin may worsen myopathy in statin users.
The news got worse. In March 2013, the HPS2-THRIVE investigators reported at the American College of Cardiology's scientific meetings that patients taking Tredaptive were also somewhat more likely to develop internal bleeding (most commonly in the stomach and the brain) and infections. They were also more likely to develop diabetes-related complications and report other gastrointestinal problems. However, it's unclear whether niacin or laropiprant was responsible for these added side effects.
In response to the findings, Merck pulled Tredaptive off the market in countries where the drug was being sold. (It was never available in the United States.)
A cloudy picture
While these disappointing results have focused specifically on niacin, other research has questioned whether raising HDL cholesterol by any means is worth pursuing for the sake of promoting heart health. In recent years, researchers have studied several experimental drugs that boost HDL but failed to prevent heart trouble (one actually appeared to cause heart attacks).
What's more, a genetic study published in 2012 in The Lancet found that people who inherit special versions of genes that promote high HDL levels have heart attacks just as often as people in the general population. Yet, even as these current studies have raised doubts about the benefits of niacin, past research on the drug clouds the picture.
A 2013 analysis in the Journal of the American College of Cardiology (JACC) identified 11 previous studies (involving close to 10,000 men and women) that collectively suggest taking niacin may lower the risk for heart attacks and other cardiovascular events by as much as 34 percent.
These studies include several in which niacin was paired with a statin. It's important to keep in mind, though, that combining the findings of many studies is risky, since a few poorly designed or executed trials may produce unreliable results that distort the overall picture.
The authors of the JACC analysis also propose that niacin may protect the heart through some means other than increasing HDL levels or altering blood fats. For instance, niacin lowers inflammation, which research suggests may trigger heart attacks.
If you take niacin
Clearly, the niacin story is more complex than doctors understood just a few years ago. At a minimum, take the recent news about this widely used drug as a cue to talk with your doctor about its place, if any, in your healthy-heart regimen. But don't stop taking niacin before speaking with your doctor. He or she may have prescribed the drug for a reason other than raising HDL cholesterol.
For example, niacin also lowers LDL cholesterol and triglycerides, an artery-clogging blood fat, by roughly 25 percent. In addition, it reduces levels of lipoprotein(a), another particle in the blood that’s been linked to heart disease.
Source: Source: Prepared by the Editors of The Johns Hopkins Medical Letter: Health After 50