Safety and efficacy of laropiprant and extended-release niacin combination in the management of mixed  dyslipidemias and primary hypercholesterolemia

Abstract

Statins form the cornerstone of pharmaceutical cardiovascular disease prevention. However, despite very effective statin intervention, the majority of events remain unpreventable. In some cases statin therapy alone is insufficient to achieve adequate lipid levels whereas other patients are unable to tolerate statins. This calls for additional treatment options. Niacin has a long history of success in reducing low-density lipoprotein cholesterol and triglycerides, and increasing high-density lipoprotein cholesterol. It was the first lipid-lowering drug to demonstrate a reduction in cardiovascular events, and remains the only one that has consistently shown benefits on surrogate outcomes when added to background therapies of other lipid-lowering drugs, including statins. Niacin’s uptake in clinical practice has been less successful due to its side-effect profile, most notable being flushing. The uncovering of the mechanism by which flushing is induced, together with the development of a prostaglandin D2 receptor inhibitor (laropiprant) which reduces this downstream flushing effect of niacin, has sparked new promise in therapeutic lipid management. It provides an additional treatment option into managing lipid abnormalities. The uptake in clinical practice of the niacin–laropiprant combination will depend on the relative improvements experienced by the patient in the side-effect profile compared to other treatment options, as well as on the the keenly-awaited outcome studies currently underway. Until these data become available guidelines and recommendations are unlikely to change and niacin’s position in therapeutic cardiovascular risk prevention will be determined by clinician opinion and experience, and patient preferences.

Large-Scale Gene-Centric Meta-analysis across 32 Studies Identifies Multiple Lipid Loci

“…For example, HCAR2 (MIM 609163), also known as niacin receptor 1, is an important biomolecular target of niacin, which is a widely prescribed drug for the treatment of dyslipidemia and which acts primarily by inhibiting hepatic DGAT-2 (MIM 606983) and thus lowers secretion of TG-rich lipoproteins and increases HDL-C levels. 75,76 The evidence from the cumulative meta-analysis of ourdata, the replication studies, and the published GLGC results suggest that further ''true'' signals might be found with less stringent p value thresholds. Given the recent deluge of available genetic data, we propose that a more careful examination is required of common variants of moderate and small effects.…”

Long Way of Evaluating Niacin for Atherosclerosis Treatment

“…Recent trials, HPS2-THRIVE and AIM-HIGH, together with long-term follow-ups, studied the efficacy of niacin in CV patients and provided somewhat controversial results (Hassan, 2014). To lower niacin's adverse effects and mediate its potency, laropiprant, a prostaglandin D2 receptor antagonist, was added to extended-release niacin in HPS2-THRIVE study (Viljoen and Wierzbicki, 2010). Better understanding of niacin mechanism of action became possible due to the establishment of the GPR109A receptor (Geisler et al, 2021).…”

Niacin in the Treatment of Hyperlipidemias in Light of New Clinical Trials: Has Niacin Lost its Place?

“…The latter cells consequently synthesize the prostaglandins D2 (PGD2) and PGE2. These compounds bind to the receptors DP1, EP2, and EP4 and cause flushing [ 19 , 20 ]. To overcome this problem, the selective antagonist of PGD2 receptors, laropiprant, has been introduced into clinical practice [ 21 ].…”