A new paradigm for managing dyslipidemia with combination therapy: laropiprant plus niacin plus simvastatin

Importance of the field: Despite effective lowering of low-density lipoprotein cholesterol (LDL-C) with statin for prevention of cardiovascular adverse events, residual risk remains high due to low high-density lipoprotein cholesterol (HDLC) levels in patients with mixed dyslipidemia. As a result, alternative treatment options to raise HDL-C are being investigated intensively. Currently, niacin is the most potent lipid lowering agent for raising HDL-C levels together with lowering of triglyceride and LDL-C. Previous clinical studies have demonstrated that niacin therapy significantly reduces the risk of cardiovascular events in high risk subjects. However, the clinical use of niacin is limited by its major adverse effect, cutaneous flushing. Although the use of extended-release (ER) formulation can reduce flushing, the tolerability and compliance of niacin remains suboptimal. A selective antagonist of prostaglandin D Type 1 receptor, laropiprant, has been investigated in a number of clinical studies and shown to be effective in reducing niacin-induced flushing. Despite the potential of laropiprant in reducing niacin-induced flushing, the long-term clinical efficacy and potential off-target side effects are not well studied. Areas covered in this reviews: In this article, the pharmacological properties, clinical efficacy and future perspective of this combination therapy of simvastatin/ER niacin/laropiprant are reviewed. What the reader will gain: Readers will understand both the mechanism and clinical effects of the combination therapy of simvastatin/ER niacin/laropiprant. Take home message: The triple combination therapy of simvastatin/ER niacin/laropiprant may reduce flushing side effects and facilitate a more comprehensive treatment for patients with mixed dyslipidemia.