Effects of Pitavastatin on Serum Lipids and High Sensitivity C-Reactive Protein in Type 2 Diabetic Patients

Abstract

Aim: Previous studies have been inconsistent results about the effects of statins on serum triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and high sensitivity C-reactive protein (hsCRP) levels. We therefore investigated the effects of pitavastatin on serum lipid profiles and hsCRP levels in patients with type 2 diabetes mellitus. Methods: The study population was 65 Japanese type 2 diabetic patients who had been administered 2 mg daily of pitavastatin and completed a 6-month follow-up. Serum lipids and hsCRP were measured before and after treatment for 1, 3, and 6 months. Results: Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and TG had significantly reduced after 1 month and remained reduced for 6 months, while HDL-C levels had significantly increased after 1 month and remained at the higher level for 6 months. Baseline median levels of hsCRP were 0.49 mg/L and showed a significant reduction to 0.37 mg/L at 6 months' treatment (p 0.001). Six-month changes in hsCRP levels were not associated with those in TC, LDL-C, HDL-C or TG. Conclusion: Pitavastatin improved serum lipid profiles and reduced serum hsCRP levels in type 2 diabetic patients with relatively low inflammation. The effect on hsCRP was not related to the effects on serum lipid profiles.

Pitavastatin: finding its place in therapy

“…Furthermore, pitavastatin is generally associated with a greater HDL-C elevating efficacy than atorvastatin, simvastatin or pravastatin that is consistently increased over the long term [Hounslow et al 2010;Ose et al 2010Ose et al , 2009Watson, 2010;Budinski et al 2009;Teramoto et al 2009Teramoto et al , 2007Stender and Hounslow, 2009;Kurihara et al 2008;Yokote and Saito, 2008]. In addition to pitavastatin's potent effects on lipid profiles, a number of pleiotropic benefits have been identified that may contribute to a reduction in residual CV risk in people with dyslipidaemia and could partly account for pitavastatin's ability to regress coronary plaques in patients with ACS [Egashira, 2009;Hiro et al 2009;Motomura et al 2009;Nakano and Ohbayashi et al 2009;Koshiyama et al 2008;Inoue et al 2007;Sagara et al 2007;Kawakami et al 2005;Kibayashi et al 2005;Han et al 2004;Hiraoka et al 2004;Morikawa et al 2004Morikawa et al , 2002Hiraoka and Yoshida, 2003;Markle et al 2003;Suzuki et al 2003]. Importantly, the safety and tolerability profiles of pitavastatin 14 mg are similar to those of atorvastatin, pravastatin, and simvastatin at doses with comparable efficacy (Table 2).…”

“…In addition to improving lipid profiles, pitavastatin significantly reduced serum CRP levels by 34.8% versus baseline (p < 0.01). Although there have been conflicting results on the efficacy of other statins on CRP-lowering in patients with diabetes [Economides et al 2004;Sommeijer et al 2004;Tan et al 2002], the KISHIMEN study [Koshiyama et al 2008] and a more recent study by Motomura and colleagues [Motomura et al 2009] showed that pitavastatin has a significant CRP-lowering effect in people with type II diabetes that is not related to reductions in lipid profile. Although the effects of pitavastatinmediated CRP lowering on CV morbidity and/or mortality have not yet been studied in clinical trials, a number of studies have shown that CRP reduction using other statins is associated with significant reductions in CV endpoints [Ridker et al , 2005de Lemos et al 2004].…”

“…During a 104-week follow up, 10.4% of pitavastatin-treated patients experienced adverse events, of which, approximately 84% were mild and only around 1% were severe. Increases in blood Plaque stabilisation Accumulation of macrophages# collagen" MMPs# [Suzuki et al 2003] Thrombosis formation TF mRNA/protein expression# PAI-I mRNA expression/antigen secretion/activity# t-PA mRNA expression/antigen secretion" TM mRNA expression/cellular antigen/transcription rate" [Markle et al 2003;Morikawa et al 2002] Inflammatory markers CRP# [Motomura et al 2009;Kibayashi et al 2005;Hiraoka and Yoshida, 2003] PTX3# [Ohbayashi et al 2009;Morikawa et al 2004] CRP, C-reactive protein; eNOS, endothelial nitric oxide synthase; ET-1, endothelin-1; ICAM-1, intercellular adhesion molecule-1; IL-8, interleukin-8; MCP-1, monocyte chemoattractant protein-1; MMP, matrix metalloproteinases; NFkb, nuclear factor kappa beta; PAI-1, plasminogen activator inhibitor-1; PTX 3, pentraxin 3; SMC, smooth muscle cell; TF, tissue factor; TM, thrombomodulin; t-PA, tissue plasminogen activator.…”

Pitavastatin: a New 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor for the treatment of hyperlipidemia

“…However, some differences between study results do exist as noted above. showed significant reductions in TC (P<0.LDL ≥120 mg/dL and TG <400 mg/dL) 60. Significant reductions in hs-CRP were also seen after 6 months of pitavastatin therapy as compared with baseline (P<0.05).…”

Pitavastatin Reduces Elevated IL-18 Levels in Japanese Subjects with Hypercholesterolemia: Sub-analysis of Kansai Investigation of Statin for Hyperlipidemic Intervention in Metabolism and Endocrinology (KISHIMEN)

“…We have previously reported that pitavastatin significantly reduced serum levels of LDL-C, remnant-like particle cholesterol (RLP-C), and hs-CRP, and raised HDL-C levels in a multi-center, prospective, open-label study, namely the Kansai Investigation of Statin for Hyperlipidemic Intervention in Metabolism and Endocrinology (KISHIMEN) 14) . Subsequently, another group demonstrated similar results using pitavastatin 21) . In this study, we sought to determine whether pitavastatin also lowers serum levels of IL-18, another inflammatory biomarker, in the same serum samples derived from the KISHIMEN study, in which hs-CRP levels were measured 14) .…”