Niacin: Time to Revisit That FDA Indication

Niacin may still be viable for lipid control in certain patients, but it’s time for the FDA to reconsider the evidence, a systematic review concluded.

Among 17 trials looking at cardiovascular disease endpoints, niacin overall held no association with cardiovascular outcome prevention in secondary prevention, fitting with the FDA’s decision to rescind that indication in 2016 after the AIM-HIGH and HPS2-THRIVE trials failed.

The only benefits for niacin were among patients not on a statin, reported Elvira D’Andrea, MD, MPH, of Brigham and Women’s Hospital in Boston, and colleagues in JAMA Network Open.

In that group, niacin monotherapy reduced revascularization (RR 0.51, 95% CI 0.37-0.72), acute coronary syndrome (RR 0.74, 95% CI 0.58-0.96), and stroke (RR 0.74, 95% CI 0.59-0.94).

However, these effects were mainly derived from two trials performed back in the 1970s and 1980s, the researchers emphasized.

The current clinical guidelines no longer recommend niacin to prevent CVD, the researchers noted. “Yet, prescription niacin [Niaspan] retains its other FDA-approved indications and is still used by hundreds of thousands of US patients, while many others use the over-the-counter versions.”

“Given substantial advancements in cardiovascular disease management since 1990, this [lipid control] indication should be restudied in current-day patients receiving usual baseline care,” they continued.

And for the indication as monotherapy in secondary prevention to reduce recurrences of nonfatal MI, the researchers “recommend that the FDA convene an advisory committee to reconsider this approved indication for niacin products, leading to a new trial, perhaps funded by the National Heart, Lung, and Blood Institute, to confirm that it remains relevant.”

Meanwhile, “we should remove it from our list of beneficial medicines and also consider stopping patients who are taking it, as it appears to be of no major benefit and may be a waste of their money,” commented John Higgins MD, MBA, of the University of Texas McGovern Medical School in Houston.

D’Andrea’s group search of clinical trials for the systematic review turned up 102 trials looking only at surrogate measures like LDL, triglycerides, or HDL-C levels. Only 17 trials reported how niacin affected one or more cardiovascular disease outcomes.

The meta-analysis involved 35,760 participants in those 17 trials with histories of dyslipidemia or cardiovascular disease, with 52.2% of patients receiving usual therapy, placebo, or other lipid-lowering agents and 47.8% being randomized to niacin arms.

Inclusion criteria were at least 6 months of follow-up, randomization, and a control group not on niacin. Exclusion criteria included a population with competing cardiovascular disease risks, failure to report events in both arms, and lack of data on HDL-C.

Limitations of the meta-analysis included differences among studies for factors like age, treatment dosage, average lipid values at baseline, sex, and duration of follow-up. The niacin study arm had a combination of bile acid or fibrate sequestrants and niacin in a few trials, but the sensitivity analysis did not include those trials and demonstrated the same results.

“Another limitation is the risk of ecological bias in the metaregression analysis. Because we assessed the association between two individual-level variables rather than trial-level variables, the results are less robust and at higher risk of bias,” the researchers wrote.

“Further prospective trials of niacin are needed to resolve this question and determine what role it may have in the current range of therapies intended to manage CVD,” the investigators concluded.