Update on niacin - Results from the HPS2-THRIVE study

In a previous blog post, niacin for dyslipidemia, we discussed the concerns regarding niacin's lack of improvement of clinically meaningful endpoints in addition to some of its adverse effects and how to deal with them.  Recently, final results of the HPS2-THRIVE study have been published.  Here are a few highlights of the results of this study.

The HPS2-THRIVE study¹ looked at more than 25,000 patients who were randomized to niacin/laropiprant or placebo.  All patients either had or were at high risk for cardiovascular disease, were given simvastatin 40 mg +/- ezetimibe 10 mg daily (depending on LDL), and were followed for a median of 3.9 years.

• In the niacin combination arm, average LDL decreased by 10 mg/dL, HDL increased by 6 mg/dL, and triglycerides decreased by 33 mg/dL compared to placebo.
• There was no difference in any of the major cardiovascular endpoints with the exception of a 0.7% reduction in 'any revascularization procedure'.
• There were significantly more fatal or nonfatal serious adverse effects in the niacin/laropiprant group (p<0.001), including skin reactions (rashes and skin ulceration), gastrointestinal effects (bleeding and peptic ulceration), diabetes effects, and musculoskeletal effects (myopathy).
• Patients with diabetes were 55% more likely to be admitted to the hospital for a disturbance in diabetes control compared to placebo and patients without diabetes were 32% more likely to be diagnosed with diabetes.

Laropiprant is an antagonist of a prostaglandin D2 receptor and has shown to be effective in reducing the flushing adverse effect of niacin.  The niacin/laropiprant combination product was approved in Europe for several years but was removed from the market in 2013 when data from the above HPS2-THRIVE study was made available.

Take home point:

• Results of the HPS2-THRIVE study confirm that there is no role for add-on niacin in high-risk patients already on statin therapy.  The lack of reduction of cardiovascular endpoints at the cost of an increase in a variety of serious adverse events leaves essentially no justifiable indication for niacin use.

References

1.  Landray MJ, Haynes R, Hopewell JC, et al.  Effects of extended-release niacin with laropiprant in high-risk patients.  N Engl J Med  2014;371(3):203-12.

photo by Garrett Ammon