3 Things to Know About Niacin and Heart Health
By HARLAN M. KRUMHOLZ, M.D.
Recent studies published in The New England Journal of Medicine are adding to concerns about the safety and effectiveness of niacin, a popular drug for the prevention of cardiovascular disease. The studies reveal that although this B vitamin can reduce triglyceride levels, raise “good” cholesterol levels (HDL) and reduce “bad” cholesterol levels (LDL), it does not produce the benefits that patients and their doctors might expect. And the studies are revealing serious harms. Here are three things you need to know about niacin.
First, these new studies failed to show that niacin reduced the risk of heart disease and stroke.
The studies found that patients taking niacin had about the same rates of heart disease, stroke and death as those who took a placebo pill with no active ingredients.
Niacin has been known to affect lipid levels since the 1950s. Scientists have examined it in countless studies, almost all of which were not designed to determine if it led to fewer heart attacks, strokes and deaths. The largest previous study to assess whether niacin reduced the risk of heart disease compared with a placebo started in the 1960s, an era that is hardly relevant to medicine today, when so many patients are taking cholesterol-lowering statins.
Therefore, scientists designed these two new studies to determine whether niacin helped patients avoid heart disease and stroke in the statin era. The National Institutes of Health sponsored an American study, and the drug company Merck funded a large international study. One tested extended-release niacin, and the other evaluated a combination of extended-release niacin and laropiprant, an agent designed to make the niacin more tolerable.
Both studies failed to show that niacin reduced the risks of heart disease, stroke and death. Researchers even stopped the American study prematurely because the possibility of finding any benefit became so remote that its continuation seemed futile. Additional follow-up analyses conducted in both studies did not show that niacin provided a convincing benefit to any group of patients.
Second, niacin causes multiple side effects, many of which are serious.
Niacin can be hard to tolerate. It frequently causes uncomfortable flushing and itching, the reason the Merck trial tested niacin with another agent designed to block these nuisance effects.
A disturbing aspect of these recent studies is that in addition to the discomfort that many patients have, they show that niacin can cause more serious side effects. In the international study, niacin increased the risk of gastrointestinal events such as diarrhea and ulcers by 28 percent; musculoskeletal problems such as muscle damage and gout by 26 percent; rashes, skin ulcerations and other serious skin-related problems by 67 percent; infections by 22 percent; and gastrointestinal bleeding or other bleeding by 38 percent. In addition, patients on niacin were 32 percent more likely to receive a diagnosis of diabetes than those not on the drug, and in those with diabetes, niacin increased the risk of serious problems with disease management by 55 percent. Safety problems were also apparent in the American study, in which those taking niacin had a higher risk of gastrointestinal problems and infections than those taking a placebo. It is the concordance of these studies in showing harms that is so convincing.
But perhaps the most striking finding of the international study occurred before the trial started. Like many large trials, the study was designed to determine if patients would tolerate the drug before they were randomly assigned to receive niacin with laropiprant or a placebo. In this so-called run-in phase of the study, a third of those who were deemed ideal candidates and received the niacin combination withdrew from the study, mainly because of skin, gastrointestinal, musculoskeletal and diabetes side effects. So, under careful study conditions, a third of the patients could not even tolerate the drug. The risks that were discovered seem all the more important, because they occurred among individuals who initially tolerated the medication.
Third, there are still experts who say that the recent studies do not provide adequate evidence to stop recommending niacin.
No study is perfect, and for niacin advocates, many of whom have spent their careers promoting and prescribing the drug, the results of the new trials evoked disbelief. I was on a panel with a prevention specialist who told an audience of doctors that it made no sense to believe the published trials when personal experience told them otherwise. He then launched into a defense of treatments like niacin.
More reasoned critiques have rightly indicated that the trials focused on high-risk patients, almost all of whom were taking statins and had low levels of LDL cholesterol, the bad stuff. They ask whether niacin might be useful in patients with different lipid profiles, or in those who cannot tolerate statins or who had not already had a diagnosis of heart disease, or in patients with an even higher risk of heart disease and stroke. They mostly question whether these trials studied populations that were already receiving intensive treatment and were unlikely to benefit from more drugs. Even the authors of the Merck-sponsored study acknowledge, in the last sentence of their article, that they cannot say whether niacin might be beneficial for patients at even higher risk of having a heart attack or stroke or those with higher LDL levels.
The predicament is that the pursuit of more trials of niacin, particularly given the harms that were recently shown, is unlikely. Uncertainty about niacin may linger, accompanied by uncertainty about which patients it may benefit. Harder to dispute will be the drug’s serious side effects. Safety issues alone, even if niacin were beneficial, should give many people reason to avoid it.
Bottom line: If you are taking niacin, talk with your doctor about whether you should continue. Many patients will probably choose to bypass a medication without clear benefit and with documented harms. For those who decide to continue taking the medication, the hope would be for an experience different from those of the tens of thousands of participants in the recent trials. If you are not taking niacin, then realize that there is little reason to start.
Harlan Krumholz is a cardiologist and the Harold H. Hines, Jr. Professor of Medicine, director of the Yale-New Haven Hospital Center for Outcomes Research and Evaluation and a director of the Robert Wood Johnson Foundation Clinical Scholars Program at Yale University School of Medicine.