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Niacin has been used for the treatment of dyslipidemia for nearly 60 years. At pharmacological doses, niacin has favorable effects on all traditionally measured lipid parameters [1,2] and it was the first lipid-lowering drug showing benefits in reducing cardiovascular disease events in the 1970s [3]. In statin-treated patients, niacin had beneficial effects shown by regression of carotid intima-media thickness [4-6], but it had no significant benefit for the hard cardiovascular endpoints in the two recent large outcome studies, the AIM-HIGH trail [7] and the HPS2-THRIVE trial [8]. However, the AIM-HIGH study was probably underpowered to show a statistically significant effect and the HPS2-THRIVE study involved patients receiving high-dose statins and sometimes additional ezetimibe with very low baseline levels of low-density lipoprotein cholesterol (LDL-C), which appears to predict a poor LDL-C response to niacin [9] and poor clinical outcome [8]. The main subgroups of patients that appeared to benefit from treatment with niacin in the HPS2-THRIVE study were those with higher baseline levels of LDL-C (greater than or equal to 77 mg/dl) or apolipoprotein B [8] suggesting that there may still a place for niacin in clinical practice, for example, in patients who cannot tolerate statins or who have high LDL-C levels despite statin treatment.
A dose-dependent cutaneous vasodilatation with flushing associated with intense erythema, tingling, itching and elevation in skin temperature is the common side-effect of niacin and this has been the main reason for patients' discontinuation and failure to titrate to therapeutic doses of niacin [10]. In some patients, more severe reactions of an allergic nature, such as urticaria, periorbital edema, conjunctivitis or nasal congestion may occur [11]. It is well established that activation of the niacin receptor, a G protein-coupled receptor (GPR-109A, now renamed as HCAR2) on Langerhans cells results in release of PGD 2 which stimulates DP1 in blood vessels causing flushing [11]. Laropiprant (MK-0524), a selective antagonist of PGD2 at the DP1 receptor, was developed to reduce the incidence and intensity of niacin-induced flushing [12]. The fixed dose combination of laropiprant 20 mg with niacin 1 g (Tredaptive® , Merck Sharp & Dohme, NJ, USA) facilitated initiation and rapid titration of high doses of niacin with minimal flushing [13]. However, laropiprant did not abolish flushing in...