Laropiprant

Hypertriglyceridemia (HTG) is considered an independent risk factor for major adverse cardiovascular events (MACE).

This study analyzed the effects of various agents on MACE risk reduction in HTG (serum triglyceride ≥ 150 mg/dl) populations by performing a network meta-analysis. We performed a frequentist network meta-analysis to conduct direct and indirect comparisons of interventions. PubMed, EMBASE, and the Cochrane library were searched for trials until Jul 6, 2020. Randomized controlled trials that reported MACE associated with agents in entire HTG populations or in subgroups were included. The primary outcome was MACE.

Of the 2005 articles screened, 21 trials including 56,471 patients were included in the analysis. The network meta-analysis results for MACE risk based on frequency data showed that eicosapentaenoic acid (EPA) (OR: 1.32; 95% CI 1.19–1.46), gemfibrozil (OR: 1.53; 95% CI 1.20–1.95), niacin plus clofibrate (OR: 2.00; 95% CI 1.23–3.25), pravastatin (OR: 1.32; 95% CI 1.15–1.52), simvastatin (OR: 2.38; 95% CI 1.55–3.66), and atorvastatin (OR: 0.55; 95% CI 0.37–0.82) significantly reduced the risk of MACE compared to the control conditions. In the subgroup analysis of HTG patients with triglycerides ≥ 200 mg/dL, bezafibrate (OR: 0.56; 95% CI 0.33–0.94), EPA (OR: 0.72; 95% CI 0.62–0.82), and pravastatin (OR: 1.33; 95% CI 1.01–1.75) significantly reduced the MACE risk.

Simvastatin had a clear advantage in reducing the risk of MACE in the entire HTG population analyzed in this meta-analysis. EPA, but not omega-3 fatty acid, was considered an effective HTG intervention. Among fibrates, gemfibrozil was most effective, though bezafibrate may significantly reduce the risk of MACE in populations with triglyceride levels of 200–300 mg/dL.Trial registration retrospectively registered in PROSPERO (CRD42020213705).

Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are n-3 polyunsaturated fatty acids (PUFAs), and are abundant in fish oil. These n-3 PUFAs have been reported to improve the lower gastrointestinal (LGI) disorders such as ulcerative colitis and Crohn's disease through their anti-inflammatory effects. However, there are few studies on the effect of n-3 PUFAs on motility of the LGI tract, such as the ileum and colon, the parts frequently affected by these inflammatory disorders. To elucidate the effects of DHA and EPA on the LGI tract motility, we performed comparative evaluation of their effects and linoleic acid (LA), an n-6 PUFA, on contractions in the ileal and colonic longitudinal smooth muscles (LSMs) isolated from guinea pigs. In the ileal and colonic LSMs, DHA and EPA (3 × 10^-5 M each) significantly inhibited contractions induced by acetylcholine (ACh), histamine, and prostaglandin (PG) F_2α (vs. control), and these effects are stronger than that of LA (3 × 10^-5 M). In the colonic LSMs, DHA and EPA also significantly inhibited contractions induced by PGD₂ (vs. control). In addition, DHA and EPA significantly inhibited CaCl₂-induced ileal and colonic LSM contractions in Ca²⁺-free 80 mM-KCl solution (vs. control). Any ileal and colonic LSM contractions induced by ACh, histamine, PGF_2α, and CaCl₂ were completely suppressed by verapamil (10^-5 M), a voltage-gated/dependent Ca²⁺ channel (VGCC/VDCC) inhibitor. These findings suggest that DHA and EPA could improve the abnormal contractile functions of the LGI tract associated with inflammatory diseases, partly through inhibition of VGCC/VDCC-dependent ileal and colonic LSM contractions.