Zielwerterreichung unter lipidsenkender Therapie mit Ezetimib/Simvastatin bei Patienten mit Atherosklerose und/oder Diabetes mellitus – eine österreichische Anwendungsbeobachtung
Tóm tắt
GRUNDLAGEN: Unter Standard-Statintherapie lassen sich etablierte Zielwerte für das LDL-Cholesterin (LDL-C) bei kardiovaskulären Risikopatienten häufig nicht erreichen. Das zusätzliche lipidsenkende Potenzial einer Ezetimib/Simvastatin-Fixkombination wurde in einer österreichweiten Anwendungsbeobachtung evaluiert. METHODIK: 3.156 Personen erfüllten mit klinisch manifester Atherosklerose und/oder Diabetes mit hohem kardiovaskulären Risiko und LDL-C-Spiegeln >113 mg/dl trotz Statinbehandlung die Einschlusskriterien und 2.903 dieser Patienten wurden bei niedergelassenen Ärzten, in Krankenhäusern und Rehabilitationzentren mit 10 mg Ezetimib und 10–40 mg Simvastatin pro Tag in Fixkombination (Inegy) behandelt. ERGEBNISSE: Im Beobachtungszeitraum von 4–12 Wochen sank das LDL-C, weitgehend unabhängig von der Statin-Vortherapie (Rosuvastatin, Atorvastatin, Simvastatin, Pravastatin, Fluvastatin, Lovastatin) und deren Dosierung (gepoolte Medianwerte), um median 27–31 % der Ausgangswerte (Mittelwert 153,1 ± 33,5 mg/dl). Insgesamt erreichten 45,3 % (10/10 mg), 43,9 % (10/20 mg) und 62,7 % (10/40 mg Ezetimib/Simvastatin) den LDL-C-Zielwert von <100 mg/dl. SCHLUSSFOLGERUNGEN: Die Therapie mit Ezetimib/Simvastatin in Fixkombination hat gegenüber etablierten Statin-Monotherapien zusätzliches LDL-C-senkendes Potenzial in klinisch relevantem Ausmaß und versetzt mehr kardiovaskuläre Risikopatienten in die Lage, das LDL-C-Ziel von unter 100 mg/dl zu erreichen.
Tài liệu tham khảo
Castelli WP. Cholesterol and lipids in the risk of coronary artery disease – the Framingham Heart Study. Can J Cardiol, 4: 5A–10A, 1988
O'Keefe JH Jr, Cordain L, Harris WH, Moe RM, Vogel R. Optimal low-density lipoprotein is 50 to 70 mg/dl: lower is better and physiologically normal. J Am Coll Cardiol, 43: 2142–2146, 2004
Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, Kirby A, Sourjina T, Peto R, Collins R, Simes R; Cholesterol Treatment Trialists' (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet, 366: 1267–1278, 2005
Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr, Clark LT, Hunninghake DB, Pasternak RC, Smith SC Jr, Stone NJ; National Heart, Lung, and Blood Institute; American College of Cardiology Foundation; American Heart Association. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation, 110: 227–239, 2004
Fourth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice. European guidelines on cardiovascular disease prevention in clinical practice: executive summary. Eur Heart J, 28: 2375–2414, 2007
Knopp RH. Drug treatment of lipid disorders. N Engl J Med, 341: 498–511, 1999
LaRosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart JC, Gotto AM, Greten H, Kastelein JJ, Shepherd J, Wenger NK; Treating to New Targets (TNT) Investigators. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med, 352: 1425–1435, 2005
Nissen SE, Nicholls SJ, Sipahi I, Libby P, Raichlen JS, Ballantyne CM, Davignon J, Erbel R, Fruchart JC, Tardif JC, Schoenhagen P, Crowe T, Cain V, Wolski K, Goormastic M, Tuzcu EM; ASTEROID Investigators. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA, 295: 1556–1565, 2006
Brown AS, Bakker-Arkema RG, Yellen L, Henley RW Jr, Guthrie R, Campbell CF, Koren M, Woo W, McLain R, Black DM. 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, 32: 665–672, 1998
EUROASPIRE II Study Group. Lifestyle and risk factor management and use of drug therapies in coronary patients from 15 countries; principal results from EUROASPIRE II Euro Heart Survey Programme. Eur Heart J, 22: 554–572, 2001
Bays HE, Moore PB, Drehobl MA, Rosenblatt S, Toth PD, Dujovne CA, Knopp RH, Lipka LJ, Lebeaut AP, Yang B, Mellars LE, Cuffie-Jackson C, Veltri EP; Ezetimibe Study Group. Effectiveness and tolerability of ezetimibe in patients with primary hypercholesterolemia: pooled analysis of two phase II studies. Clin Ther, 23: 1209–1230, 2001
Knopp RH, Gitter H, Truitt T, Bays H, Manion CV, Lipka LJ, LeBeaut AP, Suresh R, Yang B, Veltri EP; Ezetimibe Study Group. Effects of ezetimibe, a new cholesterol absorption inhibitor, on plasma lipids in patients with primary hypercholesterolemia. Eur Heart J, 24: 729–741, 2003
Gagné C, Gaudet D, Bruckert E; Ezetimibe Study Group. Efficacy and safety of ezetimibe coadministered with atorvastatin or simvastatin in patients with homozygous familial hypercholesterolemia. Circulation, 105: 2469–2475, 2002
Davidson MH, Ballantyne CM, Kerzner B, Melani L, Sager PT, Lipka L, Strony J, Suresh R, Veltri E; Ezetimibe Study Group. Efficacy and safety of ezetimibe coadministered with statins: randomised, placebo-controlled, blinded experience in 2382 patients with primary hypercholesterolemia. Int J Clin Pract, 58: 746–755, 2004
Mikhailidis DP, Sibbring GC, Ballantyne CM, Davies GM, Catapano AL. Meta-analysis of the cholesterol-lowering effect of ezetimibe added to ongoing statin therapy. Curr Med Res Opin, 23: 2009–2026, 2007
Reckless JP, Henry P, Pomykaj T, Lim ST, Massaad R, Vandormael K, Johnson-Levonas AO, Lis K, Brudi P, Allen C. 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, 62: 539–554, 2008
Robinson JG, Smith B, Maheshwari N, Schrott H. Pleiotropic effects of statins: benefit beyond cholesterol reduction? A metaregression analysis. J Am Coll Cardiol, 46: 1855–1862, 2005
Settergren M, Böhm F, Rydén L, Pernow J. Cholesterol lowering is more important than pleiotropic effects of statins for endothelial function in patients with dysglycaemia and coronary artery disease. Eur Heart J, 29: 1753–1760, 2008
Sager PT, Melani L, Lipka L, Strony J, Yang B, Suresh R, Veltri E; Ezetimibe Study Group. Effect of coadministration of ezetimibe and simvastatin on high-sensitivity C-reactive protein. Am J Cardiol, 92: 1414–1418, 2003
Kastelein JJ, Akdim F, Stroes ES, Zwinderman AH, Bots ML, Stalenhoef AF, Visseren FL, Sijbrands EJ, Trip MD, Stein EA, Gaudet D, Duivenvoorden R, Veltri EP, Marais AD, de Groot E; ENHANCE Investigators. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med, 358: 1431–1443, 2008
Fleg JL, Mete M, Howard BV, Umans JG, Roman MJ, Ratner RE, Silverman A, Galloway JM, Henderson JA, Weir MR, Wilson C, Stylianou M, Howard WJ. Effect of statins alone versus statins plus ezetimibe on carotid atherosclerosis in type 2 diabetes: the SANDS (Stop Atherosclerosis in Native Diabetics Study) trial. J Am Coll Cardiol, 52: 2198–2205, 2008
Rossebø AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, Gerdts E, Gohlke-Bärwolf C, Holme I, Kesäniemi YA, Malbecq W, Nienaber CA, Ray S, Skjaerpe T, Wachtell K, Willenheimer R; SEAS Investigators. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med, 2008, 359: 1343–1356, 2008
Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT), http://clinicaltrials.gov/show/NCT00202878
Food and Drug Administration. Update of safety review – follow-up to the January 25, 2008 early communication about an ongoing data review for ezetimibe/simvastatin (marketed as Vytorin), ezetimibe (marketed as Zetia), and simvastatin (marketed as Zocor). January 8, 2009. Available at: http://www.fda.gov/cder/drug/early_comm/ezetimibe_simvastatin200901.htm