В обзорной статье рассматриваются антигиперлипидемические эффекты нового синтетического статина – питавастатина в сравнении с подобными эффектами других статинов. Обращается внимание на способность препарата значительно увеличивать концентрацию холестерина липопротеидов высокой плотности (на 19,3%!). Рассматривается ряд важных, в том числе ранее неизвестных плейотропных эффектов препарата.
In the review article, anti-hyperlipidemic effects of a new synthetic statin, pitavastatin, are compared with similar effects of other statins. Attention is drawn to the ability of the drug to significantly increase the concentration of high-density lipoprotein cholesterol (by 19.3%!). A number of important, including previously unknown, pleiotropic effects of the drug are considered.
1. Kajinami K, Takekoshi N, Saito Y. Pitavastatin: efficacy and safety profiles of a novel synthetic HMG-CoA reductase inhibitor. Cardiovasc Drug Rev 2003; 21: 199–215.
2. Catapano AL. Pitavastatin: a different pharmacological profile. Clin Lipidol 2012; 7 (3): 3–9.
3. Инструкция по медицинскому применению лекарственного препарата Ливазо, РУ ЛП-002855–090215. / Instruktsiia po meditsinskomu primeneniiu lekarstvennogo preparata Livazo, RU LP-002855–090215. [in Russian]
4. Катапано А., Кухарчук В.В., Сергиенко И.В. и др. Питавастатин – современный статин для коррекции дислипидемии и риска сердечно-сосудистых осложнений. Резолюция экспертного совета. Атеросклероз и дислипидемии. 2017; 2: 104–6. / Katapano A., Kukharchuk V.V., Sergienko I.V. i dr. Pitavastatin – sovremennyi statin dlia korrektsii dislipidemii i riska serdechno-sosudistykh oslozhnenii. Rezoliutsiia ekspertnogo soveta. Ateroskleroz i dislipidemii. 2017; 2: 104–6. [in Russian]
5. Ose L, Budinski D, Hounslow N, Arneson V. Comparison of pitavastatin with simvastatin in primary hypercholesterolaemia or combined dyslipidaemia. Curr Med Res Opin 2009; 25: 2755–64.
6. Warrington S, Nagakawa S, Hounslow N. Comparison of the pharmacokinetics of pitavastatin by formulation and ethnic group: an open-label, single-dose, two-way crossover pharmacokinetic study in healthy Caucasian and Japanese men. Clin Drug Investig 2011; 31: 735–43.
7. Kastelein JJ, Braamskamp M. Pitavastatin: an overview of the LIVES study. Clin Lipidol 2012; 7 (3 Suppl. 1): 25–31.
8. Stender S, Budinski D, Gosho M, Hounslow N. Pitavastatin shows greater lipid-lowering efficacy over 12 weeks than pravastatin in elderly patients with primary hypercholesterolaemia or combined (mixed) dysli pidaemia. Eur J Prev Cardiol 2013; 20 (1): 40–53.
9. Budinski D, Arneson V, Hounslow N, Gratsiansky N. Pitavastatin compared with atorvastatin in primary hypercholesterolemia or combined dyslipidemia. Clin Lipidol 2009; 4 (3): 291–302.
10. Teramoto T. Pitavastatin: clinical effects from the LIVES Study. Atheroscler Suppl 2011; 12: 285–8.
11. Teramoto T, Shimano H, Yokote K, Urashima M. New evidence on pitavastatin: efficacy and safety in clinical studies. Exp Opin Pharmacother 2010; 11: 817–28.
12. Kimura K, Shimano H, Yokote K еt al. Effects of pitavastatin (LIVALO tablet) on the estimated glomerular filtration rate (eGFR) in hypercholesterolemic patients with chronic kidney disease. Sub-analysis of the LIVALO Effectiveness and Safety (LIVES) Study. J Atheroscler Thromb 2010; 17: 601–9.
13. Motomura T, Okamoto M, Kitamura T et al. Effects of pitavastatin on serum lipids and high sensitivity C-reactive protein in type 2 diabetic patients. J Atheroscler Thromb 2009; 16 (5): 546–52.
14. J-PREDICT Study Group: Japan Prevention Trial of Diabetes by Pitavastatin in Patients with Impaired Glucose Tolerance (J-PREDICT). http://clinicaltrials.gov/ct2/show/NCT00301392.
15. Chapman MJ, Orsoni A, Robillard P et al. Effect of high-dose pitavastatin on glucose homeostasis in patients at elevated risk of new-onset diabetes: insights from the CAPITAIN and PREVAIL-US studies. Curr Med Res Opin 2014; 1–10.
16. Huang C, Huang Y, Hsu B. Pitavastatin improves glycated hemoglobin in patients with poorly controlled type 2 diabetes. Diabetes Investig 2016; 7: 769–76.
17. Drew BG, Rye KA, Duffy SJ et al. The emerging role of HDL in glucose metabolism. Nat Rev Endocrinol 2012; 8: 237–45.
18. Wu X, Yu Z, Su W et al. Low levels of ApoA1 improve risk prediction of type 2 diabetes mellitus. J Clinic Lipidol 2017. http://creativecommons.org/licenses/by-nc-nd/4.0/
19. Wang Y, Fu X, Gu X et al. Effects of intensive pitavastatin therapy on glucose control in patients with non-ST elevation acute coronary syndrome. Am J Cardiovasc Dis 2017; 7 (4): 89–96.
20. Pelliccia F et al. Pharmacodynamic comparison of pitavastatin versus atorvastatin on platelet reactivite in patients with coronary artery disease treated with dual antiplatelet therapy. Circ J 2014; 78 (3): 679–84.
21. Maruyama T, Takada M, Nishibori Y et al. Comparison of preventive effect on cardiovascular events with different statins. The CIRCLE study. Circ J 2011; 75 (8): 1951–9.
22. Hagiwara N, Kawala-Wayanabe E, Koyanagi R et al. Low – density lipoprotein cholesterol targeting with pitavastatin + ezetimibe for patients with acute coronary syndrome and dyslipidemia: the HIJ-PROPER study, a prospective, open-label, randomized trial. Eur Heart J 2017; 38 (29): 2264–76.
23. Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy With Pitavastatin in Coronary Artery Disease (REAL-CAD)’. ClinicalTrials.gov, https://clinicaltrials.gov/ ct2/show/ NCT01042730.
24. Takano H, Mizuma H, Kuwabara Y et al оn behalf of the PEARL Study Investigators Effects of Pitavastatin in Japanese Patients With Chronic Heart Failure. The Pitavastatin Heart Failure Study (PEARL Study). Circ J 2013; 77: 917–25.
25. Takayama K, Taki W, Toma N et al. Effect of Pitavastatin on Preventing Ischemic Complications with Carotid Artery Stenting: A Multicenter Prospective Study – EPOCH-CAS Study. Cardiovasc Intervent Radiol 2014; 37: 1436–43.
26. Nakamura T, Obata JE, Kitta Y et al. Rapid stabilization of vulnerable carotid plaque within 1 month of pitavastatin treatment in patients with acute coronary syndrome. J Cardiovasc Pharmacol 2008; 51: 365–71.
27. Hattori K, Ozaki Y, Ismail TF et al. Impact of statin therapy on plaque characteristics as assessed by Serial OCT, grayscale and integrated backscatter-IVUS. JACC Imag 2012; 5: 169–77.
28. Hiro T, Kimura T, Morimoto T et al for the JAPAN-ACS Investigators. Effect of Intensive Statin Therapy on Regression of Coronary Atherosclerosis in Patients With Acute Coronary Syndrome A Multicenter Randomized Trial Evaluated by Volumetric Intravascular Ultrasound Using Pitavastatin Versus Atorvastatin (JAPAN-ACS [Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome] Study). J Am Coll Cardiol 2009; 54: 293–302.
29. Miayauchi K, Daida H, Morimoto D et al and Japan-ACS Investigators. Reverse vessel remodeling but not coronary plague regression could predict future cardiovascular events in ACS patients with intensive statin therapy – the extended JAPAN-ACS study. Circ J 2012; 76 (4): 825–32.
30. Davignon J. Pleiotropic effects of pitavastatin. Br J Clin Pharmacol 2011; 73 (4): 518–35.
31. Katsumoto M, Shingu T et al. Biphasic effect of HMG-CoA reductase inhibitor, pitavastatin, on vascular endothelial cells and angiogenesis. Circ J 2005; 69 (12): 1547–55.
32. Sakabe K, Fukuda N, Fukuda Y et al. Comparisons of short-and intermediate-term effects of pitavastatin versus atorvastatin on lipid profiles, fibrinolytic parameter, and endothelial function. Int J Cardiol 2008; 125 (1): 136–8.
33. Yoshida O, Kondo T, Kureishi-Bando Y et al. Pitavastatin, an HMG-CoA reductase inhibitor ameliorates endothelial function in chronic smokers. Circ J 2010; 74 (1): 195–202.
34. Ohbayashi H, Miyazawa C, Miyamoto K. Pitavastatin improves plasma pentraxin 3 and arterial stiffness in atherosclerotic patients with hypercholesterolemia. J Atheroscler Thromb 2009; 16 (4): 490–500.
35. Umeji K, Umemoto S, Itoh S et al. Comparative effects of pitavastatin and probucol on oxidative stress, Cu/Zn superoxide dismutase, PPAR-gamma, and aortic stiffness in hypercholesterolemia. Am J Physiol Heart Circ Physiol 2006; 291 (5): H2522-32.
36. Shinozaki K, Nishio Y, Ayajiki K et al. Pitavastatin restores vascular dysfunction in insulin-resistant state by inhibiting NAD (P) H oxidase activity and uncoupled endothelial nitric oxide synthase-dependent superoxide production. J Cardiovasc Pharmacol 2007; 49 (3): 122–30.
37. Wang J, Tokoro T, Matsui K et al. Pitavastatin at low dose activates endothelial nitric oxide synthase through PI3K-AKT pathway in endothelial cells. Life Sci 2005; 76 (19): 2257–68.
38. Aoki T, Kataoka H, Ishibashi R et al. Pitavastatin suppresses formation and progression of cerebral aneurysms through inhibition of the nuclear factor kappaB pathway. Neurosurgery 2009; 64 (2): 357–65.
39. Masamura K, Oida K, Kanehara H et al. Pitavastatin-induced thrombomodulin expression by endothelial cells acts via inhibition of small G proteins of the Rho family. Arterioscler Thromb Vasc Biol 2003; 23: 512–7.
40. Markle RA, Han J, Summers BD et al. Pitavastatin alters the expression of thrombotic and fibrinolytic proteins in human vascular cells. J Cell Biochem 2003; 90: 23–32.
________________________________________________
1. Kajinami K, Takekoshi N, Saito Y. Pitavastatin: efficacy and safety profiles of a novel synthetic HMG-CoA reductase inhibitor. Cardiovasc Drug Rev 2003; 21: 199–215.
2. Catapano AL. Pitavastatin: a different pharmacological profile. Clin Lipidol 2012; 7 (3): 3–9.
3. Instruktsiia po meditsinskomu primeneniiu lekarstvennogo preparata Livazo, RU LP-002855–090215. [in Russian]
4. Katapano A., Kukharchuk V.V., Sergienko I.V. i dr. Pitavastatin – sovremennyi statin dlia korrektsii dislipidemii i riska serdechno-sosudistykh oslozhnenii. Rezoliutsiia ekspertnogo soveta. Ateroskleroz i dislipidemii. 2017; 2: 104–6. [in Russian]
5. Ose L, Budinski D, Hounslow N, Arneson V. Comparison of pitavastatin with simvastatin in primary hypercholesterolaemia or combined dyslipidaemia. Curr Med Res Opin 2009; 25: 2755–64.
6. Warrington S, Nagakawa S, Hounslow N. Comparison of the pharmacokinetics of pitavastatin by formulation and ethnic group: an open-label, single-dose, two-way crossover pharmacokinetic study in healthy Caucasian and Japanese men. Clin Drug Investig 2011; 31: 735–43.
7. Kastelein JJ, Braamskamp M. Pitavastatin: an overview of the LIVES study. Clin Lipidol 2012; 7 (3 Suppl. 1): 25–31.
8. Stender S, Budinski D, Gosho M, Hounslow N. Pitavastatin shows greater lipid-lowering efficacy over 12 weeks than pravastatin in elderly patients with primary hypercholesterolaemia or combined (mixed) dysli pidaemia. Eur J Prev Cardiol 2013; 20 (1): 40–53.
9. Budinski D, Arneson V, Hounslow N, Gratsiansky N. Pitavastatin compared with atorvastatin in primary hypercholesterolemia or combined dyslipidemia. Clin Lipidol 2009; 4 (3): 291–302.
10. Teramoto T. Pitavastatin: clinical effects from the LIVES Study. Atheroscler Suppl 2011; 12: 285–8.
11. Teramoto T, Shimano H, Yokote K, Urashima M. New evidence on pitavastatin: efficacy and safety in clinical studies. Exp Opin Pharmacother 2010; 11: 817–28.
12. Kimura K, Shimano H, Yokote K еt al. Effects of pitavastatin (LIVALO tablet) on the estimated glomerular filtration rate (eGFR) in hypercholesterolemic patients with chronic kidney disease. Sub-analysis of the LIVALO Effectiveness and Safety (LIVES) Study. J Atheroscler Thromb 2010; 17: 601–9.
13. Motomura T, Okamoto M, Kitamura T et al. Effects of pitavastatin on serum lipids and high sensitivity C-reactive protein in type 2 diabetic patients. J Atheroscler Thromb 2009; 16 (5): 546–52.
14. J-PREDICT Study Group: Japan Prevention Trial of Diabetes by Pitavastatin in Patients with Impaired Glucose Tolerance (J-PREDICT). http://clinicaltrials.gov/ct2/show/NCT00301392.
15. Chapman MJ, Orsoni A, Robillard P et al. Effect of high-dose pitavastatin on glucose homeostasis in patients at elevated risk of new-onset diabetes: insights from the CAPITAIN and PREVAIL-US studies. Curr Med Res Opin 2014; 1–10.
16. Huang C, Huang Y, Hsu B. Pitavastatin improves glycated hemoglobin in patients with poorly controlled type 2 diabetes. Diabetes Investig 2016; 7: 769–76.
17. Drew BG, Rye KA, Duffy SJ et al. The emerging role of HDL in glucose metabolism. Nat Rev Endocrinol 2012; 8: 237–45.
18. Wu X, Yu Z, Su W et al. Low levels of ApoA1 improve risk prediction of type 2 diabetes mellitus. J Clinic Lipidol 2017. http://creativecommons.org/licenses/by-nc-nd/4.0/
19. Wang Y, Fu X, Gu X et al. Effects of intensive pitavastatin therapy on glucose control in patients with non-ST elevation acute coronary syndrome. Am J Cardiovasc Dis 2017; 7 (4): 89–96.
20. Pelliccia F et al. Pharmacodynamic comparison of pitavastatin versus atorvastatin on platelet reactivite in patients with coronary artery disease treated with dual antiplatelet therapy. Circ J 2014; 78 (3): 679–84.
21. Maruyama T, Takada M, Nishibori Y et al. Comparison of preventive effect on cardiovascular events with different statins. The CIRCLE study. Circ J 2011; 75 (8): 1951–9.
22. Hagiwara N, Kawala-Wayanabe E, Koyanagi R et al. Low – density lipoprotein cholesterol targeting with pitavastatin + ezetimibe for patients with acute coronary syndrome and dyslipidemia: the HIJ-PROPER study, a prospective, open-label, randomized trial. Eur Heart J 2017; 38 (29): 2264–76.
23. Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy With Pitavastatin in Coronary Artery Disease (REAL-CAD)’. ClinicalTrials.gov, https://clinicaltrials.gov/ ct2/show/ NCT01042730.
24. Takano H, Mizuma H, Kuwabara Y et al оn behalf of the PEARL Study Investigators Effects of Pitavastatin in Japanese Patients With Chronic Heart Failure. The Pitavastatin Heart Failure Study (PEARL Study). Circ J 2013; 77: 917–25.
25. Takayama K, Taki W, Toma N et al. Effect of Pitavastatin on Preventing Ischemic Complications with Carotid Artery Stenting: A Multicenter Prospective Study – EPOCH-CAS Study. Cardiovasc Intervent Radiol 2014; 37: 1436–43.
26. Nakamura T, Obata JE, Kitta Y et al. Rapid stabilization of vulnerable carotid plaque within 1 month of pitavastatin treatment in patients with acute coronary syndrome. J Cardiovasc Pharmacol 2008; 51: 365–71.
27. Hattori K, Ozaki Y, Ismail TF et al. Impact of statin therapy on plaque characteristics as assessed by Serial OCT, grayscale and integrated backscatter-IVUS. JACC Imag 2012; 5: 169–77.
28. Hiro T, Kimura T, Morimoto T et al for the JAPAN-ACS Investigators. Effect of Intensive Statin Therapy on Regression of Coronary Atherosclerosis in Patients With Acute Coronary Syndrome A Multicenter Randomized Trial Evaluated by Volumetric Intravascular Ultrasound Using Pitavastatin Versus Atorvastatin (JAPAN-ACS [Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome] Study). J Am Coll Cardiol 2009; 54: 293–302.
29. Miayauchi K, Daida H, Morimoto D et al and Japan-ACS Investigators. Reverse vessel remodeling but not coronary plague regression could predict future cardiovascular events in ACS patients with intensive statin therapy – the extended JAPAN-ACS study. Circ J 2012; 76 (4): 825–32.
30. Davignon J. Pleiotropic effects of pitavastatin. Br J Clin Pharmacol 2011; 73 (4): 518–35.
31. Katsumoto M, Shingu T et al. Biphasic effect of HMG-CoA reductase inhibitor, pitavastatin, on vascular endothelial cells and angiogenesis. Circ J 2005; 69 (12): 1547–55.
32. Sakabe K, Fukuda N, Fukuda Y et al. Comparisons of short-and intermediate-term effects of pitavastatin versus atorvastatin on lipid profiles, fibrinolytic parameter, and endothelial function. Int J Cardiol 2008; 125 (1): 136–8.
33. Yoshida O, Kondo T, Kureishi-Bando Y et al. Pitavastatin, an HMG-CoA reductase inhibitor ameliorates endothelial function in chronic smokers. Circ J 2010; 74 (1): 195–202.
34. Ohbayashi H, Miyazawa C, Miyamoto K. Pitavastatin improves plasma pentraxin 3 and arterial stiffness in atherosclerotic patients with hypercholesterolemia. J Atheroscler Thromb 2009; 16 (4): 490–500.
35. Umeji K, Umemoto S, Itoh S et al. Comparative effects of pitavastatin and probucol on oxidative stress, Cu/Zn superoxide dismutase, PPAR-gamma, and aortic stiffness in hypercholesterolemia. Am J Physiol Heart Circ Physiol 2006; 291 (5): H2522-32.
36. Shinozaki K, Nishio Y, Ayajiki K et al. Pitavastatin restores vascular dysfunction in insulin-resistant state by inhibiting NAD (P) H oxidase activity and uncoupled endothelial nitric oxide synthase-dependent superoxide production. J Cardiovasc Pharmacol 2007; 49 (3): 122–30.
37. Wang J, Tokoro T, Matsui K et al. Pitavastatin at low dose activates endothelial nitric oxide synthase through PI3K-AKT pathway in endothelial cells. Life Sci 2005; 76 (19): 2257–68.
38. Aoki T, Kataoka H, Ishibashi R et al. Pitavastatin suppresses formation and progression of cerebral aneurysms through inhibition of the nuclear factor kappaB pathway. Neurosurgery 2009; 64 (2): 357–65.
39. Masamura K, Oida K, Kanehara H et al. Pitavastatin-induced thrombomodulin expression by endothelial cells acts via inhibition of small G proteins of the Rho family. Arterioscler Thromb Vasc Biol 2003; 23: 512–7.
40. Markle RA, Han J, Summers BD et al. Pitavastatin alters the expression of thrombotic and fibrinolytic proteins in human vascular cells. J Cell Biochem 2003; 90: 23–32.
Авторы
Д.М.Аронов, М.Г.Бубнова*
ФГБУ «Национальный медицинский исследовательский центр профилактической медицины» Минздрава России. 101990, Россия, Москва, Петроверигский пер., д. 10, стр. 3 *mbubnova@gnicPM.ru
________________________________________________
D.M.Aronov, M.G.Bubnova*
National Medical Research Center of Preventive Medicine of the Ministry of Health of the Russian Federation. 101000, Russian Federation, Moscow, Petroverigskii per., d. 10, str. 3 *mbubnova@gnicPM.ru