Niacin Holds No Surprise Side Effects But Efficacy Data Forthcoming

MUNICH, Germany—An update to the largest randomized trial to date on extended-release niacin plus laropiprant vs. placebo in high-risk patients has found no unexpected adverse effects from treatment through 3-year follow-up. In interim results of the HPS2-THRIVE trial presented August 26 at the European Society of Cardiology (ESC) Congress 2012, most patients who tolerated the drug combination at 8 weeks remained compliant over the long-term.

However, the effect of treatment on vascular events (nonfatal MI, coronary death, nonfatal or fatal stroke, or revascularization) through 4-year follow-up will be not be announced until 2013, reported Jane Armitage, MBBS, of Oxford University (Oxford, United Kingdom).

For the HPS2-THRIVE trial, Dr. Armitage and colleagues screened more than 50,000 high-risk patients with occlusive arterial disease at centers in China, Scandinavia, and the United Kingdom. After excluding patients who could not tolerate the niacin therapy, the remainder began background therapy of 40 mg simvastatin with or without ezetimibe (10 mg daily). At 8 weeks, a total of 25,673 patients were randomized to niacin/laropiprant (2 mg daily) or placebo in addition to the LDL-lowering regimen.

In the current safety analysis, 76% of the niacin group and 85% of the placebo group remained complaint at a median follow-up of 3.4 years. Patients who stopped therapy largely did so because of the known effects that niacin has on the skin including flushing, pruritus, and rash and on the gastrointestinal system (table 1).

Table 1. Side Effects Cited as Reasons for Drug Cessation

Rhabdomyolysis was observed in only 7 patients (0.05%) receiving the niacin combination and 3 (0.02%) receiving placebo. Myopathy was more common at 0.54% and 0.09% of the niacin and placebo groups, respectively (RR 5.8; 95% CI 3.1-10.7).

But the “most striking finding,” Dr. Armitage said, is that when data were analyzed by region, nearly all the increase in myopathy could be attributed to China (1.13% with niacin vs. 0.18% with placebo). Two-thirds of myopathy cases occurred within the first year.

Encouragingly, niacin treatment had no clear adverse effect on liver, she noted.

Niacin Hardly New

Discussant Ulf Landmesser, MD, of the University Hospital Zurich (Zurich, Switzerland), explained that there are 3 main categories when developing therapies to target lipids: those that further lower LDL cholesterol, those that raise HDL cholesterol, and those that attempt to do both at once. Niacin/laropiprant falls into the third category he said, alongside CETP inhibitors such as anacetrapib and evacetrapib.

“Niacin was actually the first lipid-targeted therapy in clinical use” when it debuted in 1955, Dr. Landmesser said. Its underlying mechanism has become better understood over the ensuing decades and, in 2009, laropiprant coadministration was shown to reduce the flushing associated with niacin treatment, he reported.

Since its publication in the New England Journal of Medicine in December 2011, the AIM-HIGH study has led to much discussion about niacin therapy, he commented. The trial found no clinical benefit came from adding niacin to statin therapy over 36 months of follow-up, though patients derived significant improvements in HDL cholesterol and triglyceride levels.

However, Dr. Landmesser drew attention to several differences between the 2 studies. AIM-HIGH enrolled fewer than 4,000 patients and was designed to test the effect of HDL lowering, while the much larger HPS2-THRIVE trial is attempting to simultaneously lower LDL and raise HDL.

Source:

Armitage J. HPS2-THRIVE: Treatment of HDL to reduce the incidence of vascular events. Presented at: ESC Congress. August 26, 2012. Munich, Germany.

Related Stories:

• Niacin Trumps Ezetimibe as Adjunct to Chronic Statin Therapy
• NHLBI Stops High-Dose Niacin Trial Early Due to Lack of Efficacy