The Effects of High Dose Pravastatin and Low Dose Pravastatin and Ezetimibe Combination Therapy on Lipid, Glucose Metabolism and Inflammation
- 229 Downloads
Coronary artery disease (CAD) is presently the major cause of mortality and morbidity. Anti-hyperlipidemic treatment is one of the main treatment steps in the management of CAD. Statins are the cornerstones in this treatment. Ezetimibe can be reliably used, when statins prove ineffective in treatment, or to reduce their side effects. In the present study we examined the effects of high-dose pravastatin (40 mg) and low-dose pravastatin (10 mg) + ezetimibe (10 mg) combination therapy on lipid and glucose mechanism, as well as inflammation.
This study registered 100 cases. Of the cases, 50 [57.1 ± 11.1 years (24 (48%) females and 26 (52%) males)] were administered 40 mg/day pravastatin (group 1) and 50 [53.2 ± 12.2 years (27 (54%) females and 23 (46%) males)] were administered 10 mg pravastatin + 10 mg ezetimibe (group 2).
In group 1, total cholesterol fell from 231.1 ± 83.5 mg/dl to 211.3 ± 37.2 mg/dl (p = 0.03), triglyceride from 243.5 ± 96.8 mg/dl to 190.9 ± 55.2 mg/dl (p = 0.003), and LDL cholesterol from 165.7 ± 29.7 mg/dl to 133.4 ± 26.6 mg/dl (p = 0.02). In group 2, total cholesterol dropped from 250.9 ± 51.8 mg/dl to 187.9 ± 34.9 mg/dl (p = 0.001), triglyceride from 270.3 ± 158.9 mg/dl to 154.6 ± 60.7 mg/dl (p = 0.001), and LDL cholesterol from 158.1 ± 47.5 mg/dl to 116.9 ± 26.4 mg/dl (p = 0.001). Insulin resistance decreased from 4.05 ± 2.31 to 3.16 ± 1.90 (p = 0.07) in group 1 and from 2.96 ± 1.50 to 2.05 ± 0.55 (p = 0.009) in group 2. High sensitive C-reactive protein fell from 6.69 ± 6.11 mg/l to 3.02 ± 1.70 mg/l (p = 0.01) in group 1 and from 6.36 ± 2.06 mg/l to 2.68 ± 1.69 mg/l (p = 0.001) in group 2.
Both therapy regimes are effective. However, we found that low-dose pravastatin and ezetimibe combination therapy is more effective than high-dose pravastatin therapy on lipid metabolism, glucose metabolism and inflammation.
Key wordsezetimibe pravastatin hyperlipidemia inflammation insulin resistance
- 2.Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. 2001. Executive summary of the third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 285:2486–2497.CrossRefGoogle Scholar
- 3.Kastelein, J., and M. J. van Dam. 2001. A new role for combination therapy in lipid management. Br. J. Cardiol. 8:639–653.Google Scholar
- 4.Pearson, T. A., I. Laurora, H. Chu, and S. Kafonek. 2000. 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. 28(160):459–467.CrossRefGoogle Scholar
- 5.van Heek, M, C. F. France, D. S. Compton, R. L. Mcleod, N. P. Yumibe, K. B. Alton, E. J. Sybertz, and H. R. Davis, Jr. 1997. In vivo metabolism-based discovery of a potent cholesterol absorption inhibitor, SCH58235, in the rat and rhesus monkey through the identification of the active metabolites of SCH48461. J. Pharmacol. Exp. Ther. 283:157–163.PubMedGoogle Scholar
- 16.Miettinen, T. A. 2001. Cholesterol absorption inhibition: a strategy for cholesterol-lowering therapy. Drug Focus 55:710–716.Google Scholar
- 18.Shepherd, J., S. M. Cobbe, I. Ford, C. G. Isles, A. R. Lorimer, P. W. MacFarlane, J. H. McKillop, and Packard C. J. 1995. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N. Engl. J. Med. 333:1301–1307.PubMedCrossRefGoogle Scholar
- 19.Reaven, G. 1988. The Banting Lecture: the role of insulin resistance in human disease. Diabetes 37:1596–1607.Google Scholar
- 26.Grundy, S. M., B. Howard, S. Smith, Jr, R. Eckel, R. Redberg, and R. O. Bonow. 2002. Prevention Conference, VI: Diabetes and cardiovascular disease: executive summary: conference proceeding for healthcare professionals from a special writing group of the American Heart Association. Circulation 105:2231–2239.PubMedCrossRefGoogle Scholar
- 27.Reaven, G. 1994. Syndrome X: 6 years later. J. Intern. Med. Suppl. 736:13–22.Google Scholar
- 30.Haverkate, F., S. G. Thompson, S. D. Pyke, J. R. Gallimore, and M. B. Pepys. 1997. Production of C-reactive protein and risk of coronary events in stable and unstable angina European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. Lancet 349(9050):426–462.CrossRefGoogle Scholar
- 31.Pietila, K. O., A. P. Harmoinen, J. Jokiniitty, and A. I. Pasternack. 1996. Serum creactive protein concentration in acute myocardial infarction and its relationship to mortality during 24 months of follow-up in patients under thrombolytic treatment. Eur. Heart. J. 17(9):1345–1349.PubMedGoogle Scholar
- 33.Ridker, P. M., N. Rifai, M. Clearfield, J. R. Downs, S. E. Weis, J. S. Miles, and A. M. Gotto, Jr. Air Force/Texas Coronary Atherosclerosis Prevention Study Investigators. 2001. Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N. Engl. J. Med. 344:1959–1965.PubMedCrossRefGoogle Scholar