Randomized «FARVATER» study. Atorvastatin (10 and 20 mg/d) in treating patients with coronary heart disease and dyslipidemia: effects on lipids, C-reactive protein and fibrinogen levels

Aim. To compare effects of atorvastatin in the doses of 10 and 20 mg/d on lipid profile, C-reactive protein (hsCRP), fibrinogen levels, as well as vascular wall structure and function in patients with coronary heart disease (CHD) and primary hyperlipidemia (PHL). Material and methods. Fifty CHD and PHL patients were randomized to 10 or 20 mg/d atorvastatin doses (no titration), for 24-week period. Atorvastatin effects on lipids, treatment tolerability (symptoms ± increased hepatic enzymes), as well as on endothelial function, vessel elasticity and stiffness, were examined. Results. After 24 weeks of 10 mg/d atorvastatin treatment, levels of total cholesterol (TCH), triglycerides (TG), and low-density lipoprotein CH (LDL-CH) significantly decreased – by 25,4%, 21,7%, 34,9%, respectively. In 20 mg/d group, these figures were 27%, 15,2%, and 43,9%, respectively. No significant inter-group difference in LDL-CH levels was registered. No substantial CRP and fibrinogen level reduction was observed. During 24 weeks, 7 adverse events were registered, only 2 (4%) being related to atorvastatin therapy. Conclusion. In patients with CHD and PHL, atorvastatin (10-20 mg/d) decreased LDL-CH levels by 35-44%, and was well-tolerated. The therapy did not affect hsCRP and fibrinogen levels.

1. Shal'nova S.A., Deev A.D, Oganov R.G. Faktory, vliyayushchie na smertnost' ot serdechno-sosudistykh zabolevanii v rossiiskoi populyatsii. Kardiovask ter profil 2005; 4(1): 4-8.

2. Kharchenko V.I., Kokorina E.P., Koryakin M.V. i dr. Smertnost' ot osnovnykh boleznei sistemy krovoobrashcheniya v Rossii. RKZh 2005; 1(51): 5-15.

3. Demograficheskii ezhegodnik naseleniya Rossii. Goskomstat 2003.

4. Schwartz GG, Ollson AG, Ezekowitz MD, et al. Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering. (MIRACLE) study Investigators. Effects of Atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACLE study: a randomized controlled trial. JAMA 2001; 285(13): 1711-8.

5. Cannon CP, Braunwald E, McCabe CH, et al. Pravastatin or Atorvastatin evaluation and infection therapy-thrombolysis in myocardial infarction 22 investigators. Intensive versus moderate lipid-lowering with statins after acute coronary syndromes. N Engl J Med 2004; 350: 1495-504.

6. Collhoun HM, Betteridge DJ, Durrington P.N. et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 2004; 364(9435): 685-96.

7. Sever PS, Dahlof B, Poulter NR, et al. ASCOT investigators. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower than average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial Lipid Lowering Arm. (ASCOT -LLA): a Multicentre controlled lipid-lowering trial. Lancet 2003; 361: 1149-58.

8. LaRosa JC, Grundy SM, Waters DD, et al; Treating to New Targets (TNT) Investigators. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl Med 2005; 352(14): 1425-35.

9. Pedersen TR, Faergeman O, Kastelein JJP, et al. High dose atorvastatin vs usual dose simvastatin for secondary prevention after myocardial infarction. JAMA 2005; 294(19): 2437-45.

10. Nissen SE, Tuzcu EM, Schoenhagen P, Brown BG, et al. REVERSAL Investigators. Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. JAMA 2004; 3; 291(9): 1071-80.

11. Pearson TA, Laurora I, Chu H, et al. The Lipid Treatment Assessment Project (L-TAP). A multicenter survey to evaluate the percentages of dyslipidemic patients receiving lipid-lowering therapy and achieving low-density lipoprotein cholesterol goals. Arch Intern Med 2000; 160: 459-67.

12. EUROASPIRE II Study Group. Lifestyle and risk factor management and use of drug therapies inn coronary patients from 15 countries. Principal results from EUROASPIRE II Euro Heart Survey Programm. Eur Heart J 2001; 22: 554-72.

13. Ganse EV, Laforest L, Alemao E, et al. Lipid-modifying therapy and attainment of cholesterol goals in Europe:the Return on Expenditure Achieved for Lipid Therapy (REALITY) study. Curr Med Res Opin 2005; 21(9): 1389-99.

14. Susekov A V, Zubareva M.Yu, Deev A.D i dr. Osnovnye rezul'taty Moskovskogo Issledovaniya po Statinam (Moscow Statin Survey, MSS).Serdtse, 2006, v pechati.

15. Roberts WL, Multon L, Law TC, et al. Evaluation of nine automated high-sensitivity C-reactive protein methods: Implication for clinical and epidemiological applications. Part II. Clin Chem 2001; 3(47): 418-25.

16. Cumarokov A.B, Naumov V.G, Masenko V.P. S-reaktivnyi belok i serdechno-sosudistaya patologiya. Izdatel'stvo «Triada» 2006; 175 s.

17. Jones P, Kafonek S, Laurora I, Hunnghake D. Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study). Am J Cardiol 1998; 81(5): 582-7.

18. Andrews TC, Ballantyne CV, Hsia JA, et al. Achieving and maintaining National Cholesterol Education Program lowdensity lipoprotein cholesterol goals with five statins. Am J Med 2001; 111(3): 185-91.

19. Insull W, Kafonek S, Goldner D. Comparison of efficacy and safety of atorvastatin (10mg) with simvastatin (10mg) at six weeks. ASSET Investigators. Am J Card 2001; 87(5): 554-9.

20. Karalis DG, Ross AM, Vacari RM. Comparison of efficacy and safety of atorvastatin and simvastatin in patients with dyslipidemia with and without coronary heart disease. Am J Cardiol 2002; 89(6): 667-71.

21. Jones PH, McKenney JM, Karalis DG. Comparison of the efficacy and safety of atorvastatin initiated at different starting doses in patients with dyslipidemia.Evide. Based Cardiovasc Med 2005; 9(2): 98-101.

22. S c h r o t t H , Fe r e s h e t i a n AG , K n o p p R H , e t a l . A Multicenter, Placebo-Controlled, Dose-Ranging Study of Atorvastatin. J Cardiovasc Pharmacol Ther 1998; 3(2): 119-24.

23. Wierzbicki AS, Lumb PJ, Chick G, Crook MA. Comparison of therapy with simvastatin 80 mg and atorvastatin 80 mg in patients with familial hypercholesterolaemia. International J Clin Prac 1999; 53(8): 609-11.

24. Ernst E, Koenig W. Fibrinogen and cardiovascular risk. Vasc Med 1997; 2: 115-25.

25. Assmann G, Cullen P, Heinrich J, Schulte H. Hemostatic variables in the prediction of coronary risk: results of the 8 year followup of healthy men in the Munster Heart Study (PROCAM). Prospective Cardiovascular Munster Study. Isr J Med Sci 1996; 32(6): 364-70.

26. Susekov A.V. Effekt statinov na nelipidnye markery ishemicheskoi bolezni serdtsa: S-reaktivnyi belok i fibrinogen. Atmosfera-Kardiologiya 2003; 4: 21-4.

27. Ross R. Atherosclerosis - an inflammatory disease. N Engl J Med 1999; 340: 115-26.

28. Ridker PM. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation 2003; 107: 363-9.

29. Newman CB, Palmer G, Silbershatz H, Szarek M. Safety of atorvastatin derived from analysis of 44 completed trials in 9,416 patients. Am J Cardiol 2003; 92(6): 670-6.

30. Shal'nova S.A., Deev A.D. Kharakteristika patsientov vysokogo riska. Rezul'taty epidemiologicheskoi chasti nauchno-obrazovatel'noi programmy OSKAR. Kardiovask ter profil 2006; 5: 58-63