Mohamed A ABU-SAİF, Mohamed E.A. ABDELRAHİM, Ahmed A.H ALİ, Hassan A. H ALİ

Evaluate the efficacy of Simvastatin and Fluvastatin in patients with hypercholesterolemia and their effect on liver functions

The study was aimed to evaluate Simvastatin and Fluvastatin effects on patients with hypercholesterolemia. For 6 months, 141 patients administered Simvastatin (GpA), 100 administered Fluvastatin (GpB) and 100 fluctuated between them (GpC). Post treatment, in GpA, Triglycerides, total Bilirubin (T.BIL), Cholesterol and Low Density Lipoprotein (LDL) were significantly reduced. Alkaline Phosphatase (ALP) and Alanine Aminotransferase (ALT) elevated reduced in females and elevated in males. T.BIL reduced in both males and females. In GpB, Glutamyltransferase elevated and Cholesterol and LDL reduced. Albumin elevated in females and reduced in males and the opposite in Triglycerides. Significant difference between age groups in Albumin, Globulin, and ALT was found. In GpC, Asprtate Aminotransferase (AST) elevated and ALT, Cholesterol, Triglycerides and LDL reduced in all patients. Albumin and ALT elevated in males and reduced in females. Significant difference between age groups in Albumin, T.BIL and AST was found. Fluvastatin or simvastatin had variable effects on lipid parameters in patients with hypercholesterolemia and associated with mild effect on liver. Simvastatin was more effective to reach antihypercholesterolemic goal. Effects were related to gender, age and continuation on the same medication. Patients lab data periodic monitoring during therapy is useful to reach antihypercholesterolemic goal and observe any serious liver parameters elevation

PDF

___

1. Davidson MH, Toth PP. Comparative effects of lipid-lowering therapies. Prog Cardiovasc Dis. 2004;47(2):73-104.

2. stvan ES, Palnitkar M, Buchanan SK, Deisenhofer J. Crystal structure of the catalytic portion of human HMG-CoA reductase: insights into regulation of activity and catalysis. EMBO J. 2000;19(5):819-30.

3. stvan ES, Deisenhofer J. Structural mechanism for statin inhibition of HMGCoA reductase. Science. 2001;292(5519):1160.

4. Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, Brown L, Warnica JW, Arnold JMO, Wun CC. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med. 1996;335(14):1001-9.

5. Pedersen T, Kjekshus J, Berg K, Haghfelt T, Faergeman O, Thorgeirsson G. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344(8934):1383-9.

6. Gould AL, Rossouw JE, Santanello NC, Heyse JF, Furberg CD. Cholesterol reduction yields clinical benefit: impact of statin trials. Circulation. 1998;97(10):946.

7. Mantel-Teeuwisse AK, Klungel OH, Egberts TCG, Verschuren WMM, Porsius AJ, de Boer A. Failure to continue lipid-lowering drug use following the withdrawal of cerivastatin. Drug Safety. 2004;27(1):63-70.

8. Bonacini MML. Drug induced hepatotoxicity. Liver and GI Rev 2002;10:1-6.

9. Al-Salman J, Arjomand H, Kemp DG, Mittal M. Hepatocellular injury in a patient receiving rosiglitazone: a case report. Ann Intern Med. 2000;132(2):121.

10. Forman LM, Simmons DA, Diamond RH. Hepatic failure in a patient taking rosiglitazone. Ann Internal Med. 2000;132(2):118.

11. Nierenberg DW. “Did This Drug Cause My Patient’s Hepatitis?” and Related Questions. Ann Internal Med. 2002;136(6):480.

12. Ballare M, Campanini M, Airoldi G, Zaccala G, Bertoncelli M, Cornaglia G, Porzio M, Monteverde A. Hepatotoxicity of hydroxy-methylglutaryl-coenzyme A reductase inhibitors. Minerva Gastroenterol Dietol. 1992;38(1):41.

13. Molcanyiova A, Stancakova A, Javorsky M, Tkac I. Beneficial effect of simvastatin treatment on LDL oxidation and antioxidant protection is more pronounced in combined hyperlipidemia than in hypercholesterolemia. Pharmacol Res. 2006;54(3):203-7.

14. Jones P, Kafonek S, Laurora I, Hunninghake D. for the CURVES Investigators. 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.

15. Olsson AG, Eriksson M, Johnson O, Kjellström T, Lanke J, Larsen ML, Pedersen T, Tikkanen MJ, Wiklund O. A 52-week, multicenter, randomized, parallel-group, double-blind, double-dummy study to assess the efficacy of atorvastatin and simvastatin in reaching low-density lipoprotein cholesterol and triglyceride targets: The treat-to-target (3T) study* 1. Clin Ther. 2003;25(1):119-38.

16. Weng TC, Yang YHK, Lin SJ, Tai SH. A systematic review and meta analysis on the therapeutic equivalence of statins. J Clin Pharm Ther. 2010;35(2):139- 51.

17. van Dam MJ, Penn HJAM, den Hartog FR, Kragten HA, Trip MD, Buirma RJA, Kastelein JJP. A comparison of the efficacy and tolerability of titrateto-goal regimens of simvastatin and fluvastatin: a randomized, double-blind study in adult patients at moderate to high risk for cardiovascular disease. Clin Ther. 2001;23(3):467-78.

18. Bruckert E, Verpilleux MP, Dejager S, Isaacsohn J. Comparison of efficacy and safety assessment of fluvastatin in patients< 65 years versus>= 65 years of age. Am J Cardiol 2005;96(8):1142-8.

19. Koornstra J, Ottervanger J, Fehmers M, Stricker B. Clinically manifest liver lesions during use of simvastatin. Ned Tijdschr Geneeskd. 1996;140(15):846.

20. Ballare M, Campanini M, Catania E, Bordin G, Zaccala G, Monteverde A. Acute cholestatic hepatitis during simvastatin administration. Recenti Prog Med. 1991;82(4):233.

21. Boccuzzi SJ, Bocanegra TS, Walker JF, Shapiro DR, Keegan ME. Long-term safety and efficacy profile of simvastatin. Am J Cardiol. 1991;68(11):1127-31.

22. Kubota T, Fujisaki K, Itoh Y, Yano T, Sendo T, Oishi R. Apoptotic injury in cultured human hepatocytes induced by HMG-CoA reductase inhibitors. Biochem Pharmacol. 2004;67(12):2175-86.

23. Alsheikh-Ali AA, Maddukuri PV, Han H, Karas RH. Effect of the Magnitude of Lipid Lowering on Risk of Elevated Liver Enzymes, Rhabdomyolysis, and Cancer:: Insights From Large Randomized Statin Trials. J Am Coll Cardiol. 2007;50(5):409-18.

24. Scott R, Lintott C, Wilson M. Simvastatin and side effects. N Z Med J. 1991;104(924):493.

25. Darioli R, Bovet P, Brunner H, Bercher L. Evaluation of tolerance, efficacy and safety of 3-year simvastatin use in the treatment of primary hypercholesterolemia]. Schweiz Med Wochenschr. 1990;120(4):85.