• Cardiology Clinical Trials
• Lipid Disorders

Approximately two thirds of patients can tolerate extended-release (ER) niacin when combined with laropiprant, according to a prespecified interim safety and tolerability analysis of the Heart Protection Study 2: Treatment of HDL to Reduce the Incidence of Vascular Events [HPS2-THRIVE; NCT00461630] study. The addition of niacin/laropiprant to statin therapy offers a dual goal of decreasing low-density lipoprotein-cholesterol (LDL-C) and increasing high-density lipoprotein-cholesterol (HDL-C).

Niacin, the first lipid-modifying drug, is one of the most effective agents for increasing HDL-C levels. However, its use has been limited by its side effects, particularly flushing. Coadministration of laropiprant, a selective prostaglandin D antagonist, has been shown to reduce flushing. However, the drug may not reduce this side effect in all patients, as flushing can occur through other pathways.

HPS2-THRIVE includes more than 25,000 patients in Europe and China who have cardiovascular disease (CVD) and are at high risk for recurrent vascular events. The patients were randomly assigned to ER niacin 2 g/laropiprant or to placebo. All patients also received LDL-C reducing therapy with simvastatin 40 mg, with or without ezetimibe 10 mg. The study is the largest one to date to evaluate the CV benefits of increasing HDL-C levels. Jane Armitage, MD, Oxford Clinical Trial Service, Oxford, United Kingdom, reported on the safety and tolerability of the combination drug.

Patients were treated with ER niacin/laropiprant or placebo during an 8-week run-in phase prior to randomization. During this phase, 25.4% of patients in the ER niacin/laropiprant group withdrew from therapy for any medical reason; the primary reasons were cutaneous effects (primarily flushing, 11.3%) and gastrointestinal symptoms (5.5%). An additional 8.7% of patients in this group withdrew during the randomized treatment phase, again primarily because of cutaneous effects (5.1%) and gastrointestinal symptoms (3.6%). Among patients in the placebo group, 1.2% withdrew during the treatment phase because of cutaneous effects and 1.6% because of gastrointestinal symptoms.

Prof. Armitage noted that ER niacin/laropiprant was associated with a high rate of myopathy (1.13% vs 0.18% in the placebo group). This finding was seen primarily in patients of Chinese descent (62 of 69 patients with myopathy were from China). Overall, rhabdomyolysis was rare (0.05% in the treatment group and 0.02% in the placebo group). The identification of an increased risk of myopathy with niacin and simvastatin prompted the following change to the simvastatin label: “Patients of Chinese descent should not receive simvastatin 80 mg with cholesterol-modifying doses of niacin-containing products.”

Prof. Armitage reported that during the run-in phase, LDL-C levels were reduced by 20% and HDL-C levels were increased by 17%. These results differ from those in the Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes [AIM-HIGH] trial, in which LDL-C levels were reduced 5.5% and HDL-C levels were increased by 13.2% [AIM-HIGH Investigators. N Engl J Med 2011]. The AIM-HIGH trial was stopped early because of a lack of benefit of niacin. Whether the more favorable effects on LDL-C lowering and HDL-C raising in HPS2-THRIVE and better tolerability of niacin when combined with laropiprant will translate into a reduction in vascular events will have to wait until the presentation of the study's primary efficacy results in 2013.

• © 2012 MD Conference Express®