Hmg-Coa Reductase Inhibitor Comparison Essay

The discovery that 3-hydroxy-3-methyglutaryl coenzyme A reductase was a rate-determining step in the biosynthesis of cholesterol led to the discovery of inhibitors of this enzyme. To support the development of these agents (statins) as potential hypocholesterolemic drugs, a variety of preclinical studies were conducted in several animal species. Not unexpectedly due to the central role played by mevalonic acid and its products including cholesterol in development and maintenance of cellular homeostasis, administration of high dosage levels of these agents led to the expression of a broad variety of adverse effects in many different tissues. Using the tools of toxicologic pathology and classical risk assessment, these varied toxicities were evaluated by many groups relative to the conditions of use in human therapy and a perspective was developed on potential human risk. These approaches of mechanism-based risk assessment predicted that most of the adverse effects observed in animals would not be seen under conditions of human use and supported the successful introduction of one of the most important classes of human medicines.


American Heart Association. Heart and Stroke Statistics 2009 Update. 2009. Available at: http:​//wwwamericanheartorg​/downloadable/heart​/123783441267009Heart​%20and%20Stroke%20Updatepdf.


Krysiak R, Okopie AB, Herman Z. Effects of HMG-CoA reductase inhibitors on coagulation and fibrinolysis processes. Drugs. 2003;63(17):1821–1854. [PubMed: 12921488]


Balk EM, Lau J, Goudas LC, et al. Effects of statins on nonlipid serum markers associated with cardiovascular disease: a systematic review. Ann Intern Med. 2003;139(8):670–682. [PubMed: 14568856]


National Cholesterol Education Program. Sep, 2002. Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III): National Institutes of Health. NIH 02–5215. [PubMed: 12485966]


Grundy SM, Cleeman JI, Bairey Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004;110(2):227–239. [PubMed: 15249516]


Smith Jr MD SC, ScD JAR, PED SNB. AHA/ACC Guidelines for Secondary Prevention for Patients With Coronary and Other Atherosclerotic Vascular Disease: 2006 Update. JACC. 2006;47:2130–2139. [PubMed: 16697342]


Advicor Product Label. http://www​.accessdata​​/label/2006/021249s009s010s011lbl​.pdf.


Canner PL, Berge KG, Wenger NK, et al. Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J Am Coll Cardiol. 1986 Dec;8(6):1245–1255. [PubMed: 3782631]


Sweeney ME, Johnson RR. Ezetimibe: an update on the mechanism of action, pharmacokinetics and recent clinical trials. Expert Opinion On Drug Metabolism & Toxicology. 2007 Jun;3(3):441–450. [PubMed: 17539750]


Centre for Reviews and Dissemination. CRD Report Number 4. 2nd edition. 2001. Undertaking systematic reviews of research on effectiveness: CRD’s guidance for those carrying out or commissioning reviews.


Harris RP, Helfand M, Woolf SH, et al. Current methods of the U.S. Preventive Services Task Force: a review of the process. Am J Prev Med. 2001;20(3S):21–35. [PubMed: 11306229]


Rogers SL, Magliano DJ, Levison DB, et al. A dose-specific meta-analysis of lipid changes in randomized controlled trials of atorvastatin and simvastatin. Clin Ther. 2007 Feb;29(2):242–252. [PubMed: 17472817]


Wlodarczyk J, Sullivan D, Smith M. Comparison of benefits and risks of rosuvastatin versus atorvastatin from a meta-analysis of head-to-head randomized controlled trials. Am J Cardiol. 2008 Dec 15;102(12):1654–1662. [PubMed: 19064019]


Asztalos BF, Le Maulf F, Dallal GE, et al. Comparison of the effects of high doses of rosuvastatin versus atorvastatin on the subpopulations of high-density lipoproteins. Am J Cardiol. 2007 Mar 1;99(5):681–685. [PubMed: 17317371]


Ballantyne C, Bertolami M, Garcia H, et al. Am Heart J. 5. Vol. 151. 2006. Achieving LDL cholesterol, non-HDL cholesterol, and apolipoprotein B target levels in high-risk patients: Measuring Effective Reductions in Cholesterol Using Rosuvastatin therapy (MERCURY) II; pp. 975.e971–e979. [PubMed: 16644314]


Binbrek AS, Elis A, Al-Zaibag M, et al. Rosuvastatin versus atorvastatin in achieving lipid goals in patients at high risk for cardiovascular disease in clinical practice: A randomized, open-label, parallel-group, multicenter study (DISCOVERY Alpha study) Current Therapeutic Research - Clinical and Experimental. 2006;67(1):21–43. [PMC free article: PMC4052636] [PubMed: 24936119]


Clearfield MB, Amerena J, Bassand JP, et al. Comparison of the efficacy and safety of rosuvastatin 10 mg and atorvastatin 20 mg in high-risk patients with hypercholesterolemia - Prospective study to evaluate the Use of Low doses of the Statins Atorvastatin and Rosuvastatin (PULSAR) Trials [Electronic Resource] 2006;7(35) [PMC free article: PMC1779361] [PubMed: 17184550]


Deedwania P, Stone PH, Bairey Merz CN, et al. Effects of intensive versus moderate lipid-lowering therapy on myocardial ischemia in older patients with coronary heart disease: results of the Study Assessing Goals in the Elderly (SAGE) Circulation. 2007 Feb 13;115(6):700–707. [PubMed: 17283260]


Discovery-UK study group. Achieving lipid goals in real life: the DISCOVERY-UK study. British Journal of Cardiology. 2006;13:72–76.


Faergeman O, Hill L, Windler E, et al. Efficacy and tolerability of rosuvastatin and atorvastatin when force-titrated in patients with primary hypercholesterolemia: results from the ECLIPSE study. Cardiology. 2008;111(4):219–228. [PubMed: 18434729]


Herregods M-C, Daubresse J-C, Michel G, et al. Discovery Belux: comparison of rosuvastatin with atorvastatin in hypercholesterolaemia. Acta Cardiol. 2008 Aug;63(4):493–499. [PubMed: 18795588]


Kurabayashi M, Yamazaki T, Group SS. Superior benefit of aggressive lipid-lowering therapy for high- risk patients using statins: the SUBARU study--more hypercholesterolemic patients achieve Japan Atherosclerosis Society LDL-C goals with rosuvastatin therapy than with atorvastatin therapy. Journal of atherosclerosis and thrombosis. 2008 Dec;15(6):314–323. [PubMed: 19060425]


Lloret R, Ycas J, Stein M, Haffner S, Group SS. Comparison of rosuvastatin versus atorvastatin in Hispanic-Americans with hypercholesterolemia (from the STARSHIP trial) Am J Cardiol. 2006 Sep 15;98(6):768–773. [PubMed: 16950182]


Mazza F, Stefanutti C, Di Giacomo S, et al. Effects of low-dose atorvastatin and rosuvastatin on plasma lipid profiles: a long-term, randomized, open-label study in patients with primary hypercholesterolemia. American Journal of Cardiovascular Drugs. 2008;8(4):265–270. [PubMed: 18690760]


Milazzo L, Menzaghi B, Corvasce S, et al. Safety of statin therapy in HIV/hepatitis C virus-coinfected patients. Journal of Acquired Immune Deficiency Syndromes: JAIDS. 2007 Oct 1;46(2):258–260. [PubMed: 17895771]


Mulder DJ, van Haelst PL, Wobbes MH, et al. The effect of aggressive versus conventional lipid-lowering therapy on markers of inflammatory and oxidative stress. Cardiovasc Drugs Ther. 2007 Apr;21(2):91–97. [PMC free article: PMC1914252] [PubMed: 17342417]


Murakami T, Hina K, Sogou T, et al. Different effects of atorvastatin and pravastatin on hemoglobin A 1c, in hyperlipidemia patients with initially normal hemoglobin A1c. Therapeutic Research. 2006;27(11):2105–2111.


Rawlings R, Nohria A, Liu P-Y, et al. Comparison of effects of rosuvastatin (10 mg) versus atorvastatin (40 mg) on rho kinase activity in caucasian men with a previous atherosclerotic event. Am J Cardiol. 2009 Feb 15;103(4):437–441. [PMC free article: PMC2673911] [PubMed: 19195498]


Wu S-C, Shiang J-C, Lin S-L, et al. Efficacy and safety of statins in hypercholesterolemia with emphasis on lipoproteins. Heart Vessels. 2005 Sep;20(5):217–223. [PubMed: 16160904]


Andrews TC, Ballantyne CM, Hsia JA, Kramer JH. Achieving and maintaining National Cholesterol Education Program low-density lipoprotein cholesterol goals with five statins. Am J Med. 2001;111(3):185–191. [PubMed: 11530028]


Anonymous. A multicenter comparative trial of lovastatin and pravastatin in the treatment of hypercholesterolemia. The Lovastatin Pravastatin Study Group. Am J Cardiol. 1993;71(10):810–815. [PubMed: 8456759]


Assmann G, Huwel D, Schussman KM, et al. Efficacy and safety of atorvastatin and pravastatin in patients with hypercholesterolemia. European Journal of Internal Medicine. 1999;10(1):33–39.


Ballantyne CM, Blazing MA, Hunninghake DB, et al. Effect on high-density lipoprotein cholesterol of maximum dose simvastatin and atorvastatin in patients with hypercholesterolemia: Results of the Comparative HDL Efficacy and Safety Study (CHESS) Am Heart J. 2003;146(5):862–869. [PubMed: 14597936]


Berger ML, Wilson HM, Liss CL. A Comparison of the Tolerability and Efficacy of Lovastatin 20 mg and Fluvastatin 20 mg in the Treatment of Primary Hypercholesterolemia. Journal of Cardiovascular Pharmacology & Therapeutics. 1996;1(2):101–106. [PubMed: 10684406]


Bertolini S, Bon GB, Campbell LM, et al. Efficacy and safety of atorvastatin compared to pravastatin in patients with hypercholesterolemia. Atherosclerosis. 1997;130(1–2):191–197. [PubMed: 9126664]


Blasetto JW, Stein EA, Brown WV, Chitra R, Raza A. Efficacy of rosuvastatin compared with other statins at selected starting doses in hypercholesterolemic patients and in special population groups. Am J Cardiol. 2003;91(5A):3C–10C. discussion 10C. [PubMed: 12646336]


Branchi A, Fiorenza AM, Torri A, et al. Effects of low doses of simvastatin and atorvastatin on high-density lipoprotein cholesterol levels in patients with hypercholesterolemia. Clin Ther. 2001;23(6):851–857. [PubMed: 11440285]


Branchi A, Fiorenza AM, Torri A, et al. Effects of atorvastatin 10 mg and simvastatin 20 mg on serum triglyceride levels in patients with hypercholesterolemia. Curr Ther Res Clin Exp. 2001;62(5):408–415.


Brown AS, Bakker-Arkema RG, Yellen L, et al. Treating patients with documented atherosclerosis to National Cholesterol Education Program recommended low density lipoprotein cholesterol goals with atorvastatin, fluvastatin, lovastatin and simvastatin. J Am Coll Cardiol. 1998;32(3):665–672. [PubMed: 9741509]


Brown WV, Bays HE, Hassman DR, et al. Efficacy and safety of rosuvastatin compared with pravastatin and simvastatin in patients with hypercholesterolemia: a randomized, double-blind, 52-week trial. American Heart Journal. 2002;144(6):1036–1043. [PubMed: 12486428]


Crouse JRI, Frohlich J, Ose L, Mercuri M, Tobert JA. Effects of high doses of simvastatin and atorvastatin on high density lipoprotein cholesterol and apolipoprotein A I. Am J Cardiol. 1999;83(10):1476–1477. A1477. [PubMed: 10335764]


Dart A, Jerums G, Nicholson G, et al. A multicenter, double blind, one year study comparing safety and efficacy of atorvastatin versus simvastatin in patients with hypercholesterolemia. Am J Cardiol. 1997;80(1):39–44. [PubMed: 9205017]


Davidson M, Ma P, Stein EA, et al. Comparison of effects on low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with rosuvastatin versus atorvastatin in patients with type IIa or IIb hypercholesterolemia. American Journal of Cardiology. 2002;89(3):268–275. [PubMed: 11809427]


Davidson M, McKenney J, Stein E, et al. Comparison of one year efficacy and safety of atorvastatin versus lovastatin in primary hypercholesterolemia. Am J Cardiol. 1997;79(11):1475–1481. [PubMed: 9185636]


Davidson MH, Palmisano J, Wilson H, Liss C, Dicklin MR. A Multicenter, Randomized, Double-Blind Clinical Trial Comparing the Low-Density Lipoprotein Cholesterol-Lowering Ability of Lovastatin 10, 20, and 40 mg/d with Fluvastatin 20 and 40 mg/d. Clin Ther. 2003;25(11):2738–2753. [PubMed: 14693301]


Douste-Blazy P, Ribeiro VG, Seed M, et al. Comparative study of the efficacy and tolerability of simvastatin and pravastatin in patients with primary hypercholesterolaemia. Drug Invest. 1993;6:353–361.


Farmer JA, Washington LC, Jones PH, Shapiro DR, Gotto AM, Mantell G. Comparative effects of simvastatin and lovastatin in patients with hypercholesterolemia. Clin Ther. 1992;14(5):708–717. [PubMed: 1468089]


Farnier M, Portal JJ, Maigret P. Efficacy of atorvastatin compared with simvastatin in patients with hypercholesterolemia. Journal of Cardiovascular Pharmacology & Therapeutics. 2000;5(1):27–32. [PubMed: 10687671]


Frohlich J, Brun LD, Blank D, et al. Comparison of the short term efficacy and tolerability of lovastatin and simvastatin in the management of primary hypercholesterolemia. Can J Cardiol. 1993;9(5):405–412. [PubMed: 8348392]


Gentile S, Turco S, Guarino G, et al. Comparative efficacy study of atorvastatin vs simvastatin, pravastatin, lovastatin and placebo in type 2 diabetic patients with hypercholesterolaemia. Diabetes Obesity & Metabolism. 2000;2(6):355–362. [PubMed: 11225965]


Hunninghake D, Bakker-Arkema RG, Wigand JP, et al. Treating to meet NCEP recommended LDL cholesterol concentrations with atorvastatin, fluvastatin, lovastatin, or simvastatin in patients with risk factors for coronary heart disease. J Fam Pract. 1998;47(5):349–356. [PubMed: 9834769]


Illingworth RD, Crouse IJ, Hunninghake DB, et al. A comparison of simvastatin and atorvastatin up to maximal recommended doses in a large multicenter randomized clinical trial. Curr Med Res Opin. 2001;17(1):43–50. [PubMed: 11464446]


Insull W, Kafonek S, Goldner D, Zieve F. Comparison of efficacy and safety of atorvastatin (10mg) with simvastatin (10mg) at six weeks. ASSET Investigators. Am J Cardiol. 2001;87(5):554–559. [PubMed: 11230838]


Jacotot B, Benghozi R, Pfister P, Holmes D. Comparison of fluvastatin versus pravastatin treatment of primary hypercholesterolemia. French Fluvastatin Study Group. Am J Cardiol. 1995;76(2):54A–56A. [PubMed: 7604799]


Jones P, Kafonek S, Laurora I, Hunninghake D. Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study). [erratum appears in Am J Cardiol 1998 Jul 1;82(1) 128] Am J Cardiol. 1998;81(5):582–587. [PubMed: 9514454]


Jones PH, Davidson MH, Stein EA, et al. 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. [PubMed: 12860216]


Kadikoylu G, Yukselen V, Yavasoglu I, Bolaman Z. Hemostatic effects of atorvastatin versus simvastatin. Ann Pharmacother. 2003;37(4):478–484. [PubMed: 12659599]


Karalis DG, Ross AM, Vacari RM, Zarren H, Scott R. Comparison of efficacy and safety of atorvastatin and simvastatin in patients with dyslepidemia with and without coronary heart disease. Am J Cardiol. 2002;89(6):667–671. [PubMed: 11897207]


Kastelein JJ, Isaacsohn JL, Ose L, et al. Comparison of effects of simvastatin versus atorvastatin on high density lipoprotein cholesterol and apolipoprotein A I levels. Am J Cardiol. 2000;86(2):221–223. [PubMed: 10913488]


Lambrecht LJ, Malini PL, Berthe C, et al. Efficacy and tolerability of simvastatin 20 mg vs pravastatin 20 mg in patients with primary hypercholesterolemia. Acta Cardiol. 1993;48(6):541–554. [PubMed: 8122478]


Lefebvre P, Scheen A, Materne P, et al. Efficacy and tolerability of simvastatin and pravastatin in patients with primary hypercholesterolemia (multicountry comparative study) Am J Cardiol. 1992;70(15):1281–1286. [PubMed: 1442579]


Lintott CJ, Scott RS, Sutherland WH, Bremer JM. Treating hypercholesterolaemia with HMG CoA reductase inhibitors a direct comparison of simvastatin and pravastatin. Aust N Z J Med. 1993;23(4):381–386. [PubMed: 8240151]


Lucasko P, Walters EJ, Cullen EI, Niecestro R, Friedhoff LT. Efficacy of once-daily extended-release lovastatin compared to immediate-release lovastatin in patients with cholesterolemia. Curr Med Res Opin. 2004;20(1):13–18. [PubMed: 14741066]


Malini PL, Ambrosioni E, De Divitiis O, Di Somma S, Rosiello G, Trimarco B. Simvastatin versus pravastatin efficacy and tolerability in patients with primary hypercholesterolemia. Clin Ther. 1991;13(4):500–510. [PubMed: 1934003]


Marz W, Wollschlager H, Klein G, Neiss A, Wehling M. Safety of low density lipoprotein cholestrol reduction with atorvastatin versus simvastatin in a coronary heart disease population (the TARGET TANGIBLE trial) Am J Cardiol. 1999;84(1):7–13. [PubMed: 10404843]


McPherson R, Bedard J, Connelly PW, et al. Comparison of the short term efficacy and tolerability of lovastatin and pravastatin in the management of primary hypercholesterolemia. Clin Ther. 1992;14:276–291. [PubMed: 1611649]


Nash DT. Meeting national cholesterol education goals in clinical practice a comparison of lovastatin and fluvastatin in primary prevention. Am J Cardiol. 1996;78(6A):26–31. [PubMed: 8875972]


Olsson AG, Eriksson M, Johnson O, et al. 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. Clinical Therapeutics. 2003;25(1):119–138. [PubMed: 12637115]


Olsson AG, Istad H, Luurila O, et al. Effects of rosuvastatin and atorvastatin compared over 52 weeks of treatment in patients with hypercholesterolemia. American Heart Journal. 2002;144(6):1044–1051. [PubMed: 12486429]


Ose L, Scott R, Brusco O, et al. Double blind comparison of the efficacy and tolerability of simvastatin and fluvastatin in patients with primary hypercholesterolaemia. Clinical Drug Investigation. 1995;10:127–138. [PubMed: 27519196]


Paoletti R, Fahmy M, Mahla G, Mizan J, Southworth H. Rosuvastatin demonstrates greater reduction of low-density lipoprotein cholesterol compared with pravastatin and simvastatin in hypercholesterolaemic patients: a randomized, double-blind study. J Cardiovasc Risk. 2001;8(6):383–390. [PubMed: 11873095]


Recto CSI, Acosta S, Dobs A. Comparison of the efficacy and tolerability of simvastatin and atorvastatin in the treatment of hypercholesterolemia. Clin Cardiol. 2000;23(9):682–688. [PubMed: 11016019]


Bays HE, McGovern ME. Time as a variable with niacin extended-release/lovastatin vs. atorvastatin and simvastatin. Preventive Cardiology. 2005;8(4):226–233. [PubMed: 16230877]


Ferdinand KC, Clark LT, Watson KE, et al. Comparison of efficacy and safety of rosuvastatin versus atorvastatin in African-American patients in a six-week trial. Am J Cardiol. 2006 Jan 15;97(2):229–235. [PubMed: 16442368]


Fonseca FAH, Ruiz A, Cardona-Munoz EG, et al. The DISCOVERY PENTA study: a DIrect Statin COmparison of LDL-C Value--an Evaluation of Rosuvastatin therapY compared with atorvastatin. Curr Med Res Opin. 2005 Aug;21(8):1307–1315. [PubMed: 16083541]


Jukema JW, Liem A-H, Dunselman PHJM, van der Sloot JAP, Lok DJA, Zwinderman AH. LDL-C/HDL-C ratio in subjects with cardiovascular disease and a low HDL-C: results of the RADAR (Rosuvastatin and Atorvastatin in different Dosages And Reverse cholesterol transport) study. Curr Med Res Opin. 2005 Nov;21(11):1865–1874. [PubMed: 16307708]


Saklamaz A, Comlekci A, Temiz A, et al. The beneficial effects of lipid-lowering drugs beyond lipid-lowering effects: a comparative study with pravastatin, atorvastatin, and fenofibrate in patients with type IIa and type IIb hyperlipidemia. Metabolism. 2005 May;54(5):677–681. [PubMed: 15877299]


Wolffenbuttel BHR, Franken AAM, Vincent HH, Dutch Corall Study G. Cholesterol-lowering effects of rosuvastatin compared with atorvastatin in patients with type 2 diabetes -- CORALL study. J Intern Med. 2005 Jun;257(6):531–539. [PubMed: 15910557]


Schuster H, Barter PJ, Stender S, et al. Effects of switching statins on achievement of lipid goals: Measuring Effective Reductions in Cholesterol Using Rosuvastatin Therapy (MERCURY I) study. Am Heart J. 2004;147(4):705–712. [PubMed: 15077101]


Kai T, Arima S, Taniyama Y, Nakabou M, Kanamasa K. Comparison of the effect of lipophilic and hydrophilic statins on serum adiponectin levels in patients with mild hypertension and dyslipidemia: Kinki Adiponectin Interventional (KAI) Study. Clin Exp Hypertens. 2008 Oct;30(7):530–540. [PubMed: 18855257]


Ridker PM, Danielson E, Fonseca FAH, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008 Nov 20;359(21):2195–2207. [PubMed: 18997196]


Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ. 2003:1423–1427. [PMC free article: PMC162260] [PubMed: 12829554]


Chan WB, Ko GTC, Yeung VTF, et al. A comparative study of atorvastatin and simvastatin as monotherapy for mixed hyperlipidaemia in Type 2 diabetic patients. Diabetes Res Clin Pract. 2004;66(1):97–99. [PubMed: 15364167]


Paragh G, Torocsik D, Seres I, et al. Effect of short term treatment with simvastatin and atorvastatin on lipids and paraoxonase activity in patients with hyperlipoproteinaemia. Curr Med Res Opin. 2004;20(8):1321–1327. [PubMed: 15324535]


Schaefer EJ, McNamara JR, Tayler T, et al. Comparisons of effects of statins (atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin) on fasting and postprandial lipoproteins in patients with coronary heart disease versus control subjects. Am J Cardiol. 2004;93(1):31–39. [PubMed: 14697462]


Bots A, Kastelein J. on behalf of the Dutch DISCOVERY study group. Achieving lipid goals in real life: the Dutch DISCOVERY study. Int J Clin Pract. 2005;59(12):1387–1394. [PubMed: 16351669]


Insull W Jr, Ghali JK, Hassman DR, et al. Achieving low-density lipoprotein cholesterol goals in high-risk patients in managed care: comparison of rosuvastatin, atorvastatin, and simvastatin in the SOLAR trial.[see comment][erratum appears in Mayo Clin Proc. 2007 Jul;82(7):890] Mayo Clin Proc. 2007 May;82(5):543–550. [PubMed: 17493418]


van Dam M, Basart DCG, Janus C, et al. Additional efficacy of milligram-equivalent doses of atorvastatin over simvastatin. Clinical Drug Investigation. 2000;19(5):327–334.


Wolffenbuttel BH, Mahla G, Muller D, Pentrup A, Black DM. Efficacy and safety of a new cholesterol synthesis inhibitor, atorvastatin, in comparison with simvastatin and pravastatin, in subjects with hypercholesterolemia. Neth J Med. 1998;52(4):131–137. [PubMed: 9646621]


Milionis HJ, Kakafika AI, Tsouli SG, et al. Effects of statin treatment on uric acid homeostasis in patients with primary hyperlipidemia. Am Heart J. 2004;148(4):635–640. [PubMed: 15459594]


Qu H-Y, Xiao Y-W, Jiang G-H, Wang Z-Y, Zhang Y, Zhang M. Effect of atorvastatin versus rosuvastatin on levels of serum lipids, inflammatory markers and adiponectin in patients with hypercholesterolemia. Pharm Res. 2009 Apr;26(4):958–964. [PubMed: 19082693]


Schneck DW, Knopp RH, Ballantyne CM, McPherson R, Chitra RR, Simonson SG. Comparative effects of rosuvastatin and atorvastatin across their dose ranges in patients with hypercholesterolemia and without active arterial disease. American Journal of Cardiology. 2003;91(1):33–41. [PubMed: 12505568]


Schwartz GG, Bolognese MA, Tremblay BP, et al. Efficacy and safety of rosuvastatin and atorvastatin in patients with hypercholesterolemia and a high risk of coronary heart disease: a randomized, controlled trial. Am Heart J. 2004;148(1):H1–9. (e4). [PubMed: 15215813]


Strandberg TE, Feely J, Sigurdsson EL. Twelve-week, multicenter, randomized, open-label comparison of the effects of rosuvastatin 10 mg/d and atorvastatin 10 mg/d in high-risk adults: A DISCOVERY study. Clin Ther. 2004;26(11):1821–1833. [PubMed: 15639694]


Berne C, Siewert-Delle A. investigators Us. Comparison of rosuvastatin and atorvastatin for lipid lowering in patients with type 2 diabetes mellitus: results from the URANUS study. Cardiovasc Diabetol. 2005;4(7):1–11. [PMC free article: PMC1166567] [PubMed: 15935095]


Stalenhoef A, Ballantyne C, Sarti C, et al. A COmparative study with rosuvastatin in subjects with METabolic Syndrome: results of the COMETS study. Eur Heart J. 2005;26:2664–2672. [PubMed: 16143705]


Shepherd J, Hunninghake DB, Barter P, McKenney JM, Hutchinson HG. Guidelines for lowering lipids to reduce coronary artery disease risk: a comparison of rosuvastatin with atorvastatin, pravastatin, and simvastatin for achieving lipid-lowering goals. Am J Cardiol. 2003;91(5A):11C–17C. discussion 17C–19C. [PubMed: 12646338]


Milionis HJ, Rizos E, Kostapanos M, et al. Treating to target patients with primary hyperlipidaemia: comparison of the effects of ATOrvastatin and ROSuvastatin (the ATOROS study) Curr Med Res Opin. 2006 Jun;22(6):1123–1131. [PubMed: 16846545]


Deedwania PC, Hunninghake DB, Bays HE, et al. Effects of rosuvastatin, atorvastatin, simvastatin, and pravastatin on atherogenic dyslipidemia in patients with characteristics of the metabolic syndrome. Am J Cardiol. 2005;95(3):360–366. [PubMed: 15670545]


Ballantyne CM, Abate N, Yuan Z, King TR, Palmisano J. Dose-comparison study of the combination of ezetimibe and simvastatin (Vytorin) versus atorvastatin in patients with hypercholesterolemia: the Vytorin Versus Atorvastatin (VYVA) study.[see comment][erratum appears in Am Heart J. 2005 May;149(5):882] Am Heart J. 2005 Mar;149(3):464–473. [PubMed: 15864235]


Barrios V, Amabile N, Paganelli F, et al. Lipid-altering efficacy of switching from atorvastatin 10 mg/day to ezetimibe/simvastatin 10/20 mg/day compared to doubling the dose of atorvastatin in hypercholesterolaemic patients with atherosclerosis or coronary heart disease. Int J Clin Pract. 2005 Dec;59(12):1377–1386. [PubMed: 16351668]


Bays HE, Ose L, Fraser N, et al. A multicenter, randomized, double-blind, placebo-controlled, factorial design study to evaluate the lipid-altering efficacy and safety profile of the ezetimibe/simvastatin tablet compared with ezetimibe and simvastatin monotherapy in patients with primary hypercholesterolemia. Clin Ther. 2004 Nov;26(11):1758–1773. [PubMed: 15639688]


Catapano AL, Davidson MH, Ballantyne CM, et al. Lipid-altering efficacy of the ezetimibe/simvastatin single tablet versus rosuvastatin in hypercholesterolemic patients. Curr Med Res Opin. 2006 Oct;22(10):2041–2053. [PubMed: 17022864]


Ose L, Johnson-Levonas A, Reyes R, et al. A multi-centre, randomised, double-blind 14-week extension study examining the long-term safety and efficacy profile of the ezetimibe/simvastatin combination tablet. Int J Clin Pract. 2007 Sep;61(9):1469–1480. [PubMed: 17655686]


Reckless JP, Henry P, Pomykaj T, et al. Lipid-altering efficacy of ezetimibe/simvastatin 10/40 mg compared with doubling the statin dose in patients admitted to the hospital for a recent coronary event: the INFORCE study. Int J Clin Pract. 2008;62(4):539–554. [PubMed: 18266852]


Roeters van Lennep HWO, Liem AH, Dunselman PHJM, Dallinga-Thie GM, Zwinderman AH, Jukema JW. The efficacy of statin monotherapy uptitration versus switching to ezetimibe/simvastatin: results of the EASEGO study. Curr Med Res Opin. 2008 Mar;24(3):685–694. [PubMed: 18226326]


Shankar PK, Bhat R, Prabhu M, Reddy BPS, Reddy MS, Reddy M. Efficacy and tolerability of fixed-dose combination of simvastatin plus ezetimibe in patients with primary hypercholesterolemia: Results of a multicentric trial from India. Journal of Clinical Lipidology. 2007;1(4):264–270. [PubMed: 21291690]


Farnier M, Roth E, Gil-Extremera B, et al. Efficacy and safety of the coadministration of ezetimibe/simvastatin with fenofibrate in patients with mixed hyperlipidemia. Am Heart J. 2007 Feb;153(2):335.e331–338. [PubMed: 17239698]


Guyton JR, Brown BG, Fazio S, Polis A, Tomassini JE, Tershakovec AM. Lipid-altering efficacy and safety of ezetimibe/simvastatin coadministered with extended-release niacin in patients with type IIa or type IIb hyperlipidemia. J Am Coll Cardiol. 2008 Apr 22;51(16):1564–1572. [PubMed: 18420099]


Ballantyne CM, Davidson MH, McKenney J, Keller LH, Bajorunas DR, Karas RH. Comparison of the safety and efficacy of a combination tablet of niacin extended release and simvastatin vs simvastatin monotherapy in patients with increased non-HDL cholesterol (from the SEACOAST I study) Am J Cardiol. 2008 May 15;101(10):1428–1436. [PubMed: 18471454]


Bays HE, Dujovne CA, McGovern ME, et al. Comparison of once-daily, niacin extended-release/lovastatin with standard doses of atorvastatin and simvastatin (the ADvicor Versus Other Cholesterol-Modulating Agents Trial Evaluation [ADVOCATE]) The American journal of cardiology. 2003;91(6):667–672. [PubMed: 12633795]


Lin T-H, Voon W-C, Yen H-W, et al. Randomized comparative study of the effects of treatment with once-daily, niacin extended-release/lovastatin and with simvastatin on lipid profile and fibrinolytic parameters in Taiwan. Kaohsiung Journal of Medical Sciences. 2006 Jun;22(6):257–265. [PubMed: 16793562]


Laks T, Keba E, Leiner M, et al. Achieving lipid goals with rosuvastatin compared with simvastatin in high risk patients in real clinical practice: a randomized, open-label, parallel-group, multi-center study: the DISCOVERY-Beta study. Vascular Health & Risk Management. 2008;4(6):1407–1416. [PMC free article: PMC2663459] [PubMed: 19337553]


Lloret R, Haffner S, Ycas J, et al. 46th Annual Conference on Cardiovascular Disease Epidemiology and Prevention in association with the Council on Nutrition, Physical Activity, and Metabolism. Paper presented at: C-reactive protein and low-density lipoprotein cholesterol responses in the first large prospective study of statin therapy in Hispanic Americans [abstract]; 2006; Phoenix, AZ.


Comparative effectiveness of lipid-modifying agents.http:​//effectivehealthcareahrqgov​/indexcfm​/search-for-guides-reviews-and-reports​/?pageaction=displayproduct&productid=170.


Guyton JR. Niacin in cardiovascular prevention: mechanisms, efficacy, and safety. Curr Opin Lipidol. 2007 Aug;18(4):415–420. [PubMed: 17620858]


Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004 Apr 8;350(15):1495–1504. [PubMed: 15007110]


Pedersen TR, Faergeman O, Kastelein JJP, et al. High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA. 2005 Nov 16;294(19):2437–2445. [PubMed: 16287954]


Stone PH, Lloyd-Jones DM, Kinlay S, et al. Effect of intensive lipid lowering, with or without antioxidant vitamins, compared with moderate lipid lowering on myocardial ischemia in patients with stable coronary artery disease: the Vascular Basis for the Treatment of Myocardial Ischemia Study. Circulation. 2005 Apr 12;111(14):1747–1755. [PubMed: 15809368]


Tikkanen MJ, Holme I, Cater NB, et al. Comparison of efficacy and safety of atorvastatin (80 mg) to simvastatin (20 to 40 mg) in patients aged <65 versus >or=65 years with coronary heart disease (from the Incremental DEcrease through Aggressive Lipid Lowering [IDEAL] study) Am J Cardiol. 2009 Mar 1;103(5):577–582. [PubMed: 19231315]


Allhat Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT) JAMA. 2002 Dec 18;288(23):2998–3007. [PubMed: 12479764]


Tonkin A, Alyward P, Colquhoun D, Glasziou P, et al. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of intial cholesterol levels. N Engl J Med. 1998;339(19):1349–1357. [PubMed: 9841303]


Anonymous. MRC/BHF Heart Protection Study of cholesterol lowering therapy and of antioxidant vitamin supplementation in a wide range of patients at increased risk of coronary heart disease death early safety and efficacy experience. Eur Heart J. 1999;20(10):725–741. [PubMed: 10329064]


Asselbergs FW, Diercks GFH, Hillege HL, et al. Effects of fosinopril and pravastatin on cardiovascular events in subjects with microalbuminuria. Circulation. 2004;110(18):2809–2816. [PubMed: 15492322]


Colhoun HM, Betteridge DJ, Durrington PN, 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):685–696. [PubMed: 15325833]


Downs JR, Clearfield M, Weis S, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. Journal of the American Medical Association. 1998;279(20):1615–1622. [PubMed: 9613910]


Holdaas H, Fellstr AmB, Jardine AG, et al. Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a multicentre, randomised, placebo-controlled trial. Lancet. 2003;361(9374):2024–2031. [PubMed: 12814712]


Pedersen TR. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: The Scandinavian Simvastatin Survival Study (4S) Lancet. 1994;344(8934):1383–1389. [PubMed: 7968073]


Riegger G, Abletshauser C, Ludwig M, et al. The effect of fluvastatin on cardiac events in patients with symptomatic coronary artery disease during one year of treatment. Atherosclerosis. 1999;144(1):263–270. [PubMed: 10381299]


Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med. 1996;335(14):1001–1009. [PubMed: 8801446]


Sever PS, Dahlof B, Poulter NR, et al. 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 randomised controlled trial. Lancet. 2003 Apr 5;361(9364):1149–1158. [PubMed: 12686036]


Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med. 1995;333(20):1301–1307. [PubMed: 7566020]


Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002;360(9346):1623–1630. [PubMed: 12457784]


Wanner C, Krane V, Marz W, et al. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. The New England journal of medicine. 2005;353(3):238–248. [PubMed: 16034009]


Arntz HR, Agrawal R, Wunderlich W, et al. Beneficial effects of pravastatin (+/−colestyramine/niacin) initiated immediately after a coronary event (the randomized Lipid-Coronary Artery Disease [L-CAD] Study) Am J Cardiol. 2000;86(12):1293–1298. [PubMed: 11113401]


Liem AH, van Boven AJ, Veeger NJ, et al. Effect of fluvastatin on ischaemia following acute myocardial infarction: a randomized trial. Eur Heart J. 2002;23(24):1931–1937. [PubMed: 12473255]


Den Hartog FR, Van Kalmthout PM, Van Loenhout TT, Schaafsma HJ, Rila H, Verheugt FW. Pravastatin in acute ischaemic syndromes: results of a randomised placebo-controlled trial. Int J Clin Pract. 2001;55(5):300–304. [PubMed: 11452676]


de Lemos JA, Blazing MA, Wiviott SD, et al. Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. Journal of the American Medical Association. 2004;292(11):1307–1316. [PubMed: 15337732]


Schwartz GG, Olsson Ag, Ezekowitz Md, et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes the MIRACL study a randomized controlled trial. Journal of the American Medical Association. 2001;285(13):1711–1718. [PubMed: 11277825]


Thompson PL, Meredith I, Amerena J, Campbell TJ, Sloman JG, Harris PJ. Effect of pravastatin compared with placebo initiated within 24 hours of onset of acute myocardial infarction or unstable angina: the Pravastatin in Acute Coronary Treatment (PACT) trial. Am Heart J. 2004;148(1):E1–E8. [PubMed: 15215811]


Amarenco P, Bogousslavsky J, Callahan II AS. SPARCL study investigators. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355(6):549–559. [PubMed: 16899775]


Knopp R, D'Emden M, Smilde J, Pocock S. ASPEN study group. Efficacy and Safety of Atorvastatin in the Prevention of Cardiovascular End Points in Subjects with Type 2 Diabetes. Diabetes Care. 2006;29:1478–1483. [PubMed: 16801565]


Kyushu Lipid Intervention Study Group. Pravastatin use and risk of coronary events and cerebral infarction in japanese men with moderate hypercholesterolemia: the Kyushu Lipid Intervention Study. Journal of atherosclerosis and thrombosis. 2000;7(2):110–121. [PubMed: 11426582]


Nakamura H, Arakawa K, Itakura H, et al. Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial. Lancet. 2006 Sep 30;368(9542):1155–1163. [PubMed: 17011942]


Xu K, Han YL, Jing QM, et al. Lipid-modifying therapy in diabetic patients with high plasma non-high-density lipoprotein cholesterol after percutaneous coronary intervention. Experimental and Clinical Cardiology. 2007;12(1):48–50. [PMC free article: PMC2359616] [PubMed: 18650981]


Heljic B, Velija-Asimi Z, Kulic M. The statins in prevention of coronary heart diseases in type 2 diabetics. Bosnian Journal of Basic Medical Sciences. 2009 Feb;9(1):71–76. [PMC free article: PMC5645552] [PubMed: 19284399]


Herd JA, Ballantyne CM, Farmer JA, et al. Effects of fluvastatin on coronary atherosclerosis in patients with mild to moderate cholesterol elevations (Lipoprotein and Coronary Atherosclerosis Study [LCAS]) Am J Cardiol. 1997;80(3):278–286. [PubMed: 9264419]


Furberg CD, Adams HPJ, Applegate WB, et al. Effect of lovastatin on early carotid atherosclerosis and cardiovascular events. Circulation. 1994;90(4):1679–1687. [PubMed: 7734010]


Waters D, Higginson L, Gladstone P, et al. Effects of monotherapy with an HMG CoA reductase inhibitor on the progression of coronary atherosclerosis as assessed by serial quantitative arteriography. The Canadian Coronary Atherosclerosis Intervention Trial. Circulation. 1994;89(3):959–968. [PubMed: 8124836]


Blankenhorn DH, Azen SP, Kramsch DM, et al. Coronary angiographic changes with lovastatin therapy. The Monitored Atherosclerosis Regression Study (MARS). The MARS Research Group. Ann Intern Med. 1993;119(10):969–976. [PubMed: 8214993]


Pitt B, Mancini GB, Ellis SG, Rosman HS, Park JS, McGovern ME. Pravastatin limitation of atherosclerosis in the coronary arteries (PLAC I): reduction in atherosclerosis progression and clinical events. PLAC I investigation. J Am Coll Cardiol. 1995;26(5):1133–1139. [PubMed: 7594023]


Crouse JR, Byington RP, Bond MG, et al. Pravastatin, Lipids, and Atherosclerosis in the Carotid Arteries (PLAC-II) Am J Cardiol. 1995;75(7):455–459. [PubMed: 7863988]


Salonen R, Nyyssonen K, Porkkala E, et al. Kuopio Atherosclerosis Prevention Study (KAPS). A population-based primary preventive trial of the effect of LDL lowering on atherosclerotic progression in carotid and femoral arteries. Circulation. 1995;92(7):1758–1764. [PubMed: 7671358]


Sato S, Kobayashi T, Awata N, et al. Randomized, controlled trial of secondary prevention of coronary sclerosis in normocholesterolemic patients using pravastatin: Two-year follow-up of the prevention of coronary sclerosis study. Curr Ther Res Clin Exp. 2001;62(6):473–485.


Jukema JW, Bruschke AV, van Boven AJ, et al. Effects of lipid lowering by pravastatin on progression and regression of coronary artery disease in symptomatic men with normal to moderately elevated serum cholesterol levels. The Regression Growth Evaluation Statin Study (REGRESS) Circulation. 1995;91(10):2528–2540. [PubMed: 7743614]


Simoons MI, Saelman JPM, Deckers JW, et al. Effect of simvastatin on coronary atheroma The Multicentre Anti Atheroma Study (MAAS) Lancet. 1994;344(8923):633–638. [PubMed: 7864934]


Bestehorn HP, Rensing UFE, Roskamm H, et al. The effect of simvastatin on progression of coronary artery disease. Eur Heart J. 1997;18(2):226–234. [PubMed: 9043838]


Teo KK, Burton JR, Buller CE, et al. Long term effects of cholesterol lowering and angiotensin converting enzyme inhibition on coronary atherosclerosis The Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT) Circulation. 2000;102(15):1748–1754. [PubMed: 11023927]


Post Coronary Artery Bypass Graft Trial Investigators. The effect of aggressive lowering of low density lipoprotein cholesterol levels and low dose anticoagulation on obstructive changes in saphenous vein coronary artery bypass grafts. The Post Coronary Artery Bypass Graft Trial Investigators. [erratum appears in N Engl J Med 1997 Dec 18;337(25) 1859] N Engl J Med. 1997;336(3):153–162. [PubMed: 8992351]


Bertrand ME, McFadden EP, Fruchart JC, et al. Effect of pravastatin on angiographic restenosis after coronary balloon angioplasty. The PREDICT Trial Investigators. Prevention of Restenosis by Elisor after Transluminal Coronary Angioplasty. J Am Coll Cardiol. 1997;30(4):863–869. [PubMed: 9316510]


Flaker GC, Warnica JW, Sacks FM, et al. Pravastatin prevents clinical events in revascularized patients with average cholesterol concentrations. Cholesterol and Recurrent Events CARE Investigators. J Am Coll Cardiol. 1999;34(1):106–112. [PubMed: 10399998]


Kleemann A, Eckert S, von Eckardstein A, et al. Effects of lovastatin on progression of non dilated and dilated coronary segments and on restenosis in patients after PTCA. The cholesterol lowering atherosclerosis PTCA trial (CLAPT) Eur Heart J. 1999;20(19):1393–1406. [PubMed: 10487800]


Serruys PW, Foley DP, Jackson G, et al. A randomized placebo controlled trial of fluvastatin for prevention of restenosis after successful coronary balloon angioplasty; final results of the fluvastatin angiographic restenosis (FLARE) trial. Eur Heart J. 1999;20(1):58–69. [PubMed: 10075142]


Weintraub WS, Boccuzzi SJ, Klein JL, et al. Lack of effect of lovastatin on restenosis after coronary angioplasty. Lovastatin Restenosis Trial Study Group. N Engl J Med. 1994;331(20):1331–1337. [PubMed: 7935702]


Kayikcioglu M, Can L, Kultursay H, Payzin S, Turkoglu C. Early use of pravastatin in patients with acute myocardial infarction undergoing coronary angioplasty. Acta Cardiol. 2002 Aug;57(4):295–302. [PubMed: 12222700]


Pitt B, Waters D, Brown WV, et al. Aggressive lipid lowering therapy compared with angioplasty in stable coronary artery disease. Atorvastatin versus Revascularization Treatment Investigators. N Engl J Med. 1999;341(1):70–76. [PubMed: 10395630]


Serruys PWJC, de Feyter P, Macaya C, et al. Fluvastatin for prevention of cardiac events following successful first percutaneous coronary intervention: a randomized controlled trial. JAMA. 2002 Jun 26;287(24):3215–3222. [PubMed: 12076217]


Athyros VG, Papageorgiou AA, Mercouris BR, et al. Treatment with atorvastatin to the National Cholesterol Education Program goal versus "usual" care in secondary coronary heart disease prevention. The GREek Atorvastatin and Coronary heart-disease Evaluation (GREACE) Study. Curr Med Res Opin. 2002;18(4):220–228. [PubMed: 12201623]


Koren MJ, Hunninghake DB, Investigators A. Clinical outcomes in managed-care patients with coronary heart disease treated aggressively in lipid-lowering disease management clinics: the alliance study. J Am Coll Cardiol. 2004 Feb;44(9):1772–1779. [PubMed: 15519006]


LaRosa JC. Is aggressive lipid-lowering effective and safe in the older adult? Clin Cardiol. 2005 Sep;28(9):404–407. [PubMed: 16250262]


Sever PS, Dahlof B, Poulter NR, et al. Rationale, design, methods and baseline demography of participants of the Anglo-Scandinavian Cardiac Outcomes Trial. ASCOT investigators. Journal of Hypertension. 2001;19(6):1139–1147. [PubMed: 11403364]


Sever PS, Dahlof B, Poulter NR, et al. Anglo-Scandinavian Cardiac Outcomes Trial: a brief history, rationale and outline protocol. Journal of Human Hypertension. 2001;15(Suppl 1):S11–12. [PubMed: 11685901


Leave a Reply

Your email address will not be published. Required fields are marked *