Save 2.20. CAS The following reviews will discuss the potential benefits of pitavastatin versus other statins in the treatment of patients with dyslipidemia and MetS or T2D, focusing on its effects on HDL-C quantity and quality, its potential impact on atherosclerosis and CV risk, and its metabolic characteristics that reduce the risk of drug interactions. A further meta-analysis showed that the potential diabetogenic effects of statins may be dose related [14]. However, independent predictors for statin-associated T2D appear to include elevated levels of baseline FPG, BMI, blood pressure and fasting triglycerides [17]. Koh KK, Quon MJ, Han SH, Lee Y, Kim SJ, Shin EK: Atorvastatin causes insulin resistance and increases ambient glycemia in hypercholesterolemic patients. Whereas the risk of death is directly associated with levels of fasting plasma glucose (FPG) in the diabetic range (>5.6 mmol/l; 100 mg/dl), there appears to be only a modest correlation between FPG levels in the nondiabetic range (3.9 to 5.6 mmol/l; 70 to 100 mg/dl) [4]. Consistent with this observation, a post hoc analysis of intravascular ultrasound data from 1,455 people in four prospective randomized clinical trials showed that statin-associated changes in HDL-C were inversely associated with the progression of coronary atherosclerosis even in patients with low levels of LDL-C [61]. Similarly, a comparison of glycaemic control between T2D patients receiving atorvastatin 10 mg, pravastatin 10 mg or pitavastatin 2 mg/day (n = 279) showed that glycaemic parameters (arbitrary blood glucose levels and HbA1c) only increased among atorvastatin-treated patients [24]. Yokote K, Bujo H, Hanaoka H, Shinomiya M, Mikami K, Miyashita Y, Nishikawa T, Kodama T, Tada N, Saito Y. Multicenter collaborative randomized parallel group comparative study of pitavastatin and atorvastatin in Japanese hypercholesterolemic patients: collaborative study on hypercholesterolemia drug intervention and their benefits for atherosclerosis prevention (CHIBA study). Data from the National Health and Nutrition Examination Survey (1999 to 2000) showed that 93.1%, 73.0%, and 35.9% of US adults had 1, 2, and 3 modifiable risk factors for CV disease, respectively [4]. 2011, 39: 789-803. J-PREDICT Study Group: Japan prevention trial of diabetes by pitavastatin in patients with impaired glucose tolerance (J-PREDICT). Was 21.99. The choice of statin should therefore depend on the needs of the individual patient. Grover SA, Kaouache M, Joseph L, Barter P, Davignon J. Terms and Conditions, Statins in cardiometabolic disease: what makes pitavastatin different? By using this website, you agree to our This is particularly important in patients with T2D and MetS because obesity and high levels of glycated hemoglobin are directly related to low levels of HDL-C and high triglyceride. The term cardiometabolic disease encompasses a range of lifestyle-related conditions, including Metabolic syndrome (MetS) and type 2 diabetes (T2D), that are characterized by different combinations of cardiovascular (CV) risk factors, including dyslipidemia, abdominal obesity, hypertension, hyperglycemia/insulin resistance, and vascular inflammation. Europe PMC is an archive of life sciences journal literature. Numerous studies show that lowering low-density lipoprotein-cholesterol (LDL-C) levels using statins can significantly reduce CV risk in people with and without T2D, with no lower limit beyond which LDL-C-lowering is not beneficial [16-23]. Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, Kirby A, Sourjina T, Peto R, Collins R, Simes R: Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. World Health Organization Diabetes Statistics. High-density lipoprotein cholesterol and cardiovascular disease. For example, the Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) study (n = 17,802) showed a significant 3.0% versus 2.4% increase in incident T2D among healthy adults treated with rosuvastatin 20 mg/day versus placebo for 1.9 years (P = 0.01) [12]. Future studies should therefore assess the effects of statins on HDL quality as well as quantity. The choice of statin should therefore depend on the needs of the individual patient. Bookshelf (Suppl 1), S3 (2013). However, this study also showed that the addition of fenofibrate to conventional statin treatment had no effect on event rates in people with normal levels of TG and/or HDL-C. To date, the only lipid-lowering studies in which drug-induced elevations in HDL-C have been found to correlate with reductions in CV risk involve statins [56-60]. This article has been published as part of Cardiovascular Diabetology Volume 12 Supplement 1, 2013: Statins in cardiometabolic disease: what makes pitavastatin different? Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Analysis of data from the PROVE-IT TIMI 22 trial showed that, among the 3,382 patients without preexisting T2D, HbA1c levels increased by 0.12% in patients treated with pravastatin 40 mg and by 0.30% in those receiving atorvastatin 80 mg (P <0.0001) [23]. Together, these studies suggest that the duration of hyperglycaemia might contribute to the association between T2D and vascular risk. All articles have undergone the journal's standard peer review process. 2017 Jan 7;16(1):4. doi: 10.1186/s12933-016-0486-2. 1 One of the key risk factors for ED is high cholesterol. Evaluating the incremental benefits of raising high-density lipoprotein cholesterol levels during lipid therapy after adjustment for the reductions in other blood lipid levels. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. For example, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study found that the primary event rate (a composite of nonfatal myocardial infarction, stroke or CV death) was reduced from 17.3% to 12.4% in the subgroup of T2D patients with both low baseline levels of HDL-C (34 mg/dl or 0.88 mol/l) and high baseline TG (204 mg/dl or 2.3 mmol/l) [52]. Numerous studies have shown that lowering low-density lipoprotein-cholesterol (LDL-C) levels using statins can significantly reduce CV risk in people with and without T2D or MetS. Nat Commun. Yokote K, Saito Y: Influence of statins on glucose tolerance in patients with type 2 diabetes mellitus: subanalysis of the collaborative study on hypercholesterolemia drug intervention and their benefits for atherosclerosis prevention (CHIBA study). Ose L, Budinski D, Hounslow N, Arneson V. Long-term treatment with pitavastatin is effective and well tolerated by patients with primary hypercholesterolemia or combined dyslipidemia. 2002, 106: 3143-3421. Pitavastatin is used together with a proper diet to lower high cholesterol levels and triglyceride (fat) levels in the blood and increase good cholesterol (HDL) in patients with primary hyperlipidemia or mixed dyslipidemia. eCollection 2017. Pitavastatin is a product marketed by the sponsor of the supplement. Pitavastatin is a relatively newly developed cholesterol lowering agent (statin) that is associated with mild, asymptomatic and self-limited serum aminotransferase elevations during therapy, but has had limited use and has yet to be linked with clinically apparent acute liver injury. Pitavastatin is more effective in increasing high-density lipoprotein cholesterol (HDL-C) compared to other statins. Consequently, the recent European Society of Cardiology/European Atherosclerosis Society Guidelines for the Management of Dyslipidemia have included low HDL-C levels in their latest CV risk assessment charts [6,9,39]. 2008, 359: 2195-2207. CAS Metabolic syndrome (MetS), for example characterized by three or more of the following: abdominal obesity, atherogenic dyslipidemia, hypertension, and/or insulin resistance with or without glucose intolerance [6-10] is associated with a twofold to fourfold increased risk of stroke, a threefold to fourfold increased risk of myocardial infarction [11,12], and a fivefold to ninefold higher risk of developing type 2 diabetes (T2D) [13]. Your US state privacy rights, Events per 1,000 patient-years; weights are from random-effects analysis. Of these, cardiovascular (CV) diseases were the most common, accounting for approximately 30% of all deaths globally, followed by cancers (13%), chronic lung diseases (7%) and diabetes (2%). 2009, 16: 297-298. Lancet. N Engl J Med. However, the reduction in events (2.9 per 200 T2D patients treated over 5 years) was far more modest than that achieved either with lipid-lowering therapy (8.2 fewer CV events for each mmol/l reduction in low-density lipoprotein-cholesterol) or with antihypertensive treatment (12.5 fewer events per 4 mmHg reduction in systolic blood pressure) [1]. The following reviews will discuss the potential benefits of pitavastatin versus other statins in the treatment of patients with dyslipidemia and MetS or T2D, focusing on its effects on HDL-C quantity and quality, its potential impact on atherosclerosis and CV risk, and its metabolic characteristics that reduce the risk of drug interactions. Manninen V, Tenkanen L, Koskinen P, Huttunen JK, Manttari M, Heinonen OP, Frick MH. However, the literature suggests that the beneficial effects of most statins on CV risk continue to outweigh their diabetogenic risks and that statins should remain as first-line therapy for the majority of people with dyslipidaemia and metabolic syndrome or T2D. These risk factors individually and interdependently increase the risk of CV and cerebrovascular events, and represent one of the biggest health challenges worldwide today. Epub 2013 May 30. A meta-analysis of 102 prospective studies (n = 698,782) from the Emerging Risk Factors Collaboration demonstrated that T2D confers approximately a twofold excess risk for a wide range of vascular diseases, including coronary heart disease (CHD; hazard ratio (HR) = 2.00, 95% confidence interval (CI) = 1.83 to 2.19), ischaemic stroke (HR = 2.27, 95% CI = 1.95 to 2.65), haemorrhagic stroke (HR = 1.56, 95% CI = 1.19 to 2.05), and other vascular deaths (HR = 1.73, 95% CI = 1.51 to 1.98) (Figure 1) [2]. Although statins are generally safe and well tolerated, conflicting data exist regarding the diabetogenic effects of some statins. Sviridov D, Nestel P, Watts G. Statins and metabolism of high density lipoprotein. Ginsberg HN, Elam MB, Lovato LC, Crouse JR III, Leiter LA, Linz P, Friedewald WT, Buse JB, Gerstein HC, Probstfield J, Grimm RH, Ismail-Beigi F, Bigger JT, Goff DC Jr, Cushman WC, Simons-Morton DG, Byington RP. Yamakawa T, Takano T, Tanaka S, Kadonosono K, Terauchi Y: Influence of pitavastatin on glucose tolerance in patients with type 2 diabetes mellitus. 19.79. 2011, 364: 829-841. Statin diabetogenicity: guidance for clinicians. Accessibility 2006;24:S17S24. Pitavastatin is used together with a proper diet to lower high cholesterol levels and triglyceride (fat) levels in the blood and increase good cholesterol (HDL) in patients with primary hyperlipidemia or mixed dyslipidemia. Bethesda, MD 20894, Web Policies Beyond low-density lipoprotein: addressing the atherogenic lipid triad in type 2 diabetes mellitus and the metabolic syndrome. The proposed explanation for these findings is that statin-induced HDL elevations stimulate the 'reverse cholesterol transport' pathway, a process in which excess cholesterol is removed from peripheral cells and transported to the liver via HDL for excretion into bile [49]. Accessibility Summary Statins are a common medications people take to lower cholesterol and treat heart disease. Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease: the Bezafibrate Infarction Prevention (BIP) study. 2012, 59: E1692-10.1016/S0735-1097(12)61693-3. Pitavastatin: clinical effects from the LIVES Study. World Congress for Prevention of Diabetes. Nicholls SJ, Brandrup-Wognsen G, Palmer M, Barter PJ. Stender S, Hounslow N. Robust efficacy of pitavastatin and comparable safety to pravastatin. 10.1016/j.atherosclerosissup.2012.06.001. Genest J, McPherson R, Frohlich J, Anderson T, Campbell N, Carpentier A, Couture P, Dufour R, Fodor G, Francis GA, Grover S, Gupta M, Hegele RA, Lau DC, Leiter L, Lewis GF, Lonn E, Mancini GB, Ng D, Pearson GJ, Sniderman A, Stone JA, Ur E. 2009 Canadian Cardiovascular Society/Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adult 2009 recommendations. doi: 10.1186/1475-2840-12-S1-S2. However, independent predictors for statin-associated T2D appear to include elevated levels of baseline FPG, BMI, blood pressure and fasting triglycerides. Waters DD, Ho JE, DeMicco DA, Breazna A, Arsenault BJ, Wun CC, Kastelein JJ, Colhoun H, Barter P: Predictors of new-onset diabetes in patients treated with atorvastatin: results from 3 large randomized clinical trials. 10.1016/j.jacc.2010.10.047. Thus, although effective glycaemic control is important for the prevention/management of T2D, other risk factors must be addressed to effectively reduce CV risk. An official website of the United States government. Springer Nature. Yusuf S, Hawken S, Ounpuu S, Dans T, Avezurm A, Lanas F, McQueen M, Budaj A, Pais P, Varigos J, Lisheng L. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Pitavastatin is a product marketed by the sponsor of the supplement. In contrast, the West of Scotland Coronary Prevention Study (WOSCOPS; n = 5,974) showed that, compared with placebo, pravastatin was associated with a 30% reduction (P = 0.042) in the hazard of developing T2D after 5 years [13]. 3 Altmetric Metrics Abstract Statins effectively lower low-density lipoprotein-cholesterol (LDL-C) and reduce cardiovascular risk in people with dyslipidemia and cardiometabolic diseases such as Metabolic syndrome (MetS) or type 2 diabetes (T2D). 2012, 59: E1659-10.1016/S0735-1097(12)61660-X. The main mechanism of Zypitamag metabolism is conjugation with glucuronic acid through liver glucuronosyltransferases leading to the formation of pitavastatin lactone. ( 4S ) stender S, Hounslow N. Robust efficacy of pitavastatin and comparable safety to pravastatin 16 1... ( 1 ):4. doi: 10.1186/s12933-016-0486-2 's standard peer review process, Joseph,! Are from random-effects analysis other statins: E1692-10.1016/S0735-1097 ( 12 ) 61660-X key risk for... 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