Nicotinic acid + larodiorant. Laropiprant adds its own adverse effects.

When cholesterol levels remain high despite appropriate lifestyle measures, the choice of lipid-lowering drug should focus on products that have been shown to prevent fatal and nonfatal cardiovascular events. On this basis, simvastatin and pravastatin, unlike sustained-release nicotinic acid, are first-line options. A fixed-dose combination of nicotinic acid and laropiprant is authorised in the European Union for the treatment of lipid disorders, either alone or together with a statin. The role of laropiprant, a type 1 prostaglandin D2 receptor antagonist, is to prevent the flushing caused by nicotinic acid. The nicotinic acid + laropiprant combination, used alone or simultaneously with a statin, has only been tested for its effect on surrogate lipid endpoints, not for its ability to prevent cardiovascular events. Three comparative trials in a total of about 4000 patients showed that laropiprant partly prevented the flushing due to sustained-release nicotinic acid. However, about one in three patients still had at least moderately intense flushing at the outset of treatment, while about half the patients subsequently had flushing on up to 3 days a week. Compared with sustained-release nicotinic acid alone, laropiprant + nicotinic acid combination therapy provokes more gastrointestinal disorders, more hypersensitivity reactions, and more transaminase and creatine phosphokinase elevations. Through its effect on prostaglandin D2 and thromboxane A2, laropiprant also has effects on blood coagulation, with uncertain clinical consequences. Animal and human data argue against the use of the nicotinic acid + laropiprant combination during pregnancy and breast-feeding. In practice, patients with hypercholesterolaemia need drugs with well-documented clinical efficacy, and this excludes the nicotinic acid + laropiprant combination.