ROSUVASTATIN - THE MOST POTENT STATIN IN CARDIOVASCULAR DISEASE PREVENTION

Rosuvastatin is a statin with maximum hypolipidemic effect, to date, which makes it one of the most frequently prescribed lipid-lowering medications. The drug has been widely studied in large international randomized clinical trials and proven to be highly effective. Administration of rosuvastatin at doses of up to 40 mg/day allows to decrease low-density lipoprotein cholesterol (LDL-C) levels by 55-63%, triglyceride levels by 28% and to significantly increase the level of high-density lipoprotein cholesterol by 10-14%. The effectiveness of rosuvastatin for primary prevention of CV complications has been indicated in high and very high risk patients, as well as in intermediate-risk persons and patients with mildly elevated base LDL-C level. The ability of rosuvastatin to suppress the progression of atherosclerosis has been demonstrated by intravascular ultrasound of coronary arteries and by magnetic resonance imaging of carotid arteries. Rosuvastatin is a hydrophilic statin with high hepatoselectivity, low systemic bioavailability (very limited penetration of rosuvastatin into extrahepatic tissues and, hence, lower risk of myotoxicity) and minimal involvement of P450 cytochrome in its metabolism (mostly mediated by 2C9 enzyme), which provides for good tolerability of the drug. High hepatoselectivity and the absence of any significant interaction with cytochrome P450 system mitigate the likelihood of side effects and drug interactions. The above mentioned characteristics of rosuvastatin enable its effective and safe use in treating a wide range of patients.

rosuvastatin, hypercholesterolemia, atherosclerosis, cardiovascular disease, cardiovascular risk

1. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. Catapano A.L., Graham I., De Backer G., et al.; Authors/Task Force Members; Additional Contributor. Eur Heart J. 2016;37(39):2999-3058.

2. Diagnosis and correction of lipid disorders for the prevention and treatment of atherosclerosis. Russian guidelines. VI revision. Moscow: 2017;44p. [in Russian].

3. Grundy S.M., Cleeman J.I., Mertz C.N., et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. Circulation. 2004;110(2):227-239.

4. Mills E.J., Rachlis B., Wu P., et al. Primary prevention of cardiovascular mortality and events with statin treatments. A network meta-analysis involving more than 65,000 patients. J Am Coll Cardiol. 2008;52:1769-1781.

5. Cholesterol Treatment Trialists’ (CTT) Collaboration, Baigent C., Blackwell L., Emberson J., et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670-1681. DOI: 10.1016/S0140-6736(10)61350-5.

6. McKenney J.M., Jones P.H., Adamczyk M.A., et al.; STELLAR Study Group. Comparison of the efficacy of rosuvastatin versus atorvastatin, simvastatin, and pravastatin in achieving lipid goals: results from the STELLAR trial. Curr Med Res Opin. 2003;19(8):689-698.

7. Schuster H. The GALAXY Program: an update on studies investigating efficacy and tolerability of rosuvastatin for reducing cardiovascular risk. Expert Rev Cardiovasc Ther. 2007;5(2):177-193.

8. Barter P.J., Brandrup-Wognsen G., Palmer M.K., Nicholls S.J. Effect of statins on HDL-C: a complex process unrelated to changes in LDL-C: analysis of the VOYAGER Database. J Lipid Res. 2010;51(6):1546-1553. DOI: 10.1194/jlr.P002816.

9. Jones P.H., Davidson M.H., Stein E.A., et al.; STELLAR Study Group. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR Trial). Am J Cardiol. 2003;92(2):152-160.

10. Toth P.P., Dayspring T.D. Drug safety evaluation of rosuvastatin. Expert Opin Drug Saf. 2011;10(6):969-986.

11. 2016;4(25):21-29. / Ezhov M.V., Sergienko I.V., Rozhkova T.A., et al. Russian Guidelines on Familial Hypercholesterolemia Diagnosis and Treatment. Atherosclerosis and dyslipidaemias. 2016;4(25):21-29. [in Russian].

12. Watts G.F., Gidding S., Wierzbicki A.S., et al. Integrated guidance on the care of familial hypercholesterolaemia from the International FH Foundation. Int J Cardiol. 2014;171:309-325.

13. Wiegman A., Gidding S.S., Watts G.F., et al.; European Atherosclerosis Society Consensus Panel. Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment. Eur Heart J. 2015;36(36):2425-2437. DOI: 10.1093/eurheartj/ehv157.

14. Reiner Z. Impact of early evidence of atherosclerotic changes on early treatment in children with familial hypercholesterolemia. Circ Res. 2014;114:233-235.

15. Ridker P.M.; JUPITER Study Group. Rosuvastatin in the primary prevention of cardiovascular disease among patients with low levels of low-density lipoprotein cholesterol and elevated highsensitivity C-reactive protein: rationale and design of the JUPITER trial. Circulation. 2003;108(19):2292-2297.

16. Ridker P.M., Danielson E., Fonseca F.A., et al.; JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195-2207.

17. Buckley D.I., Fu R., Freeman M., et al. C-reactive protein as a risk factor for coronary heart disease: a systematic review and metaanalyses for the U.S. Preventive Services Task Force. Ann Intern Med. 2009;151(7):483-495.

18. US Preventive Services Task Force, Bibbins-Domingo K., Grossman D.C., Curry S.J., et al., Pignone MP. Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: US Preventive Services Task Force Recommendation Statement. JAMA. 2016;316(19):1997-2007. DOI: 10.1001/jama.2016.15450.

19. Yusuf S., Bosch J., Dagenais G., et al.; HOPE-3 Investigators. Cholesterol lowering in intermediate-risk persons without cardiovascular disease. N Engl J Med. 2016;374(21):2021-2031.

20. Glynn R.J., Koenig W., Nordestgaard B.G., et al. Rosuvastatin for primary prevention in older persons with elevated C-reactive protein and low to average low-density lipoprotein cholesterol levels: exploratory analysis of a randomized trial. Ann Intern Med. 2010;152:488-496,W174.

21. Nissen S.E., Nicholls S.J., Sipahi I., et al.; ASTEROID Investigators. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA. 2006;295(13):1556-1565.

22. Underhill H.R., Yuan C., Zhao X.Q., et al. Effect of rosuvastatin therapy on carotid plaque morphology and composition in moderately hypercholesterolemic patients: a high-resolution magnetic resonance imaging trial. Am Heart J. 2008;155(3):584. e1-8. DOI: 10.1016/j.ahj.2007.11.018.

23. Puri R., Libby P., Nissen S.E., et al. Long-term effects of maximally intensive statin therapy on changes in coronary atheroma composition: insights from SATURN. Eur Heart J Cardiovasc Imaging. 2014;15(4):380-388. DOI: 10.1093/ehjci/jet251.

24. Kini A.S., Baber U., Kovacic J.C., et al. Changes in plaque lipid content after short-term intensive versus standard statin therapy: the YELLOW trial (reduction in yellow plaque by aggressive lipidlowering therapy). J Am Coll Cardiol. 2013;62(1):21-29. DOI: 10.1016/j.jacc.2013.03.058.

25. Kini A.S., Vengrenyuk Y., Shameer K., et al. Intracoronary Imaging, Cholesterol Efflux, and Transcriptomes After Intensive Statin Treatment: The YELLOW II Study. J Am Coll Cardiol. 2017;69(6):628-640. DOI: 10.1016/j.jacc.2016.10.029.

26. Takayama T., Komatsu S., Ueda Y., et al.; ALTAIR study group. Comparison of the Effect of Rosuvastatin 2.5 mg vs 20 mg on Coronary Plaque Determined by Angioscopy and Intravascular Ultrasound in Japanese With Stable Angina Pectoris (from the Aggressive Lipid-Lowering Treatment Approach Using Intensive Rosuvastatin for Vulnerable Coronary Artery Plaque [ALTAIR] Randomized Trial). Am J Cardiol. 2016;117(8):1206-1212. DOI: 10.1016/j.amjcard.2016.01.013.

27. Crouse J.R. 3rd, Raichlen J.S., Riley W.A., et al.; METEOR Study Group. Effect of rosuvastatin on progression of carotid intima-media thickness in low-risk individuals with subclinical atherosclerosis: the METEOR Trial. JAMA. 2007;297(12):1344-1353.

28. Braamskamp M.J.A.M., Langslet G., McCrindle B.W., et al. Effect of Rosuvastatin on Carotid Intima-Media Thickness in Children With Heterozygous Familial Hypercholesterolemia: The CHARON Study (Hypercholesterolemia in Children and Adolescents Taking Rosuvastatin Open Label). Circulation. 2017;136(4):359-366. DOI: 10.1161/CIRCULATIONAHA.116.025158.

29. McTaggart F. Comparative pharmacology of rosuvastatin. Atherosclerosis. 2003;Suppl4:9-14.

30. Neuvonen PJ. Drug interactions with HMG-CoA reductase inhibitors (statins): the importance of CYP enzymes, transporters and pharmacogenetics. Curr Opin Investig Drugs. 2010;11(3):323-332.

31. Bailey D.G., Dresser G.K. Interactions between grapefruit juice and cardiovascular drugs. Am J Cardiovasc Drugs. 2004;4(5):281-297.

32. Schachter M. Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update. Fundam Clin Pharmacol. 2005;19:117-126.

33. Martin P.D., Mitchell P.D., Schneck D.W. Pharmacodynamic effects and pharmacokinetics of a new HMG-CoA reductase inhibitor, rosuvastatin, after morning or evening administration in healthy volunteers. Br J Clin Pharmacol. 2002;54(5):472-477.

34. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm#substrates. The University of Washington Drug Interaction Database. 2011.

35. Benes L.B., Bassi N.S., Davidson M.H. The Risk of Hepatotoxicity, New Onset Diabetes and Rhabdomyolysis in the Era of HighIntensity Statin Therapy: Does Statin Type Matter? Prog Cardiovasc Dis. 2016;59(2):145-152.

36. Keating A.J., Campbell K.B., Guyton J.R. Intermittent nondaily dosing strategies in patients with previous statin-induced myopathy. Ann Pharmacother. 2013;47:398-404.

37. Kostapanos M.S., Milionis H.J., Elisaf M.S. Rosuvastatinassociated adverse effects and drug-drug interactions in the clinical setting of dyslipidemia. Am J Cardiovasc Drugs. 2010;10(1):11-28.

38. Kiser J.J., Gerber J.G., Predhomme J.A., et al. Drug/Drug interaction between lopinavir/ritonavir and rosuvastatin in healthy volunteers. J Acquir Immune Defic Syndr. 2008;47(5):570-578.

39. Simonson S.G., Raza A., Martin P.D., et al. Rosuvastatin pharmacokinetics in heart transplant recipients administered an antirejection regimen including cyclosporine. Clin Pharmacol Ther. 2004;76(2):167-177.

40. Bergman E., Matsson E.M., Hedeland M., et al. Effect of a single gemfibrozil dose on the pharmacokinetics of rosuvastatin in bile and plasma in healthy volunteers. J Clin Pharmacol. 2010;50(9):1039-1049.

41. Simonson S.G., Martin P.D., Mitchell P.D., et al. Effect of rosuvastatin on warfarin pharmacodynamics and pharmacokinetics. J Clin Pharmacol. 2005;45(8):927-934.

42. Cooper K.J., Martin P.D., Dane A.L., et al. The effect of erythromycin on the pharmacokinetics of rosuvastatin. Eur J Clin Pharmacol. 2003;59(1):51-56.

43. Simonson S.G., Martin P.D., Warwick M.J., et al. The effect of rosuvastatin on oestrogen & progestin pharmacokinetics in healthy women taking an oral contraceptive. Br J Clin Pharmacol. 2004;57(3):279-286.

44. Bergman E., Hedeland M., Bondesson U., Lennern s H. The effect of acute administration of rifampicin and imatinib on the enterohepatic transport of rosuvastatin in vivo. Xenobiotica. 2010;40(8):558-568.

45. Zhang W., Deng S., Chen X.P., et al. Pharmacokinetics of rosuvastatin when coadministered with rifampicin in healthy males: a randomized, single-blind, placebo-controlled, crossover study. Clin Ther. 2008;30(7):1283-1289.

46. Fellstr m B.C., Jardine A.G., Schmieder R.E., et al.; AURORA Study Group. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med. 2009;360(14):1395-1407.

47. Tonelli M., Wanner C.; Kidney Disease: Improving Global Outcomes Lipid Guideline Development Work Group Members. Lipid management in chronic kidney disease: synopsis of the Kidney Disease: Improving Global Outcomes 2013 clinical practice guideline. Ann Intern Med. 2014;160:182.

48. Fonarow GC. Randomized clinical outcome trials of statins in heart failure. Heart Fail Clin. 2008;4(2):225-229.

49. Tavazzi L., Maggioni A.P., Marchioli R., et al.; Gissi-HF Investigators. Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372(9645):1231-1239. DOI: 10.1016/S0140-6736(08)61240-4