Systematic review: Comparative effectiveness and harms of combination therapy and monotherapy for dyslipidemia

Annals of Internal Medicine

Volumn 151, Issue 9, 2009, Pages 622-630

  Sharma, Mukul ^a   Ansari, Mohammed T ^b   Abou Setta, Ahmed M ^c   Soares Weiser, Karla ^d   Ooi, Teik Chye ^a   Sears, Margaret ^e   Yazdi, Fatemeh ^b   Tsertsvadze, Alexander ^b   Moher, David ^f  

^a UNIVERSITY OF OTTAWA   (Canada)

^b CHILDREN S HOSPITAL OF EASTERN ONTARIO   (Canada)

^c UNIVERSITY OF ALBERTA   (Canada)

^d Enhance Reviews   (Israel)

^e RR 1   (Canada)

^f OTTAWA HOSPITAL RESEARCH INSTITUTE   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

AMINOTRANSFERASE; ANTILIPEMIC AGENT; ATORVASTATIN; BILE ACID SEQUESTRANT; CREATINE KINASE; EZETIMIBE; FIBRIC ACID DERIVATIVE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LOW DENSITY LIPOPROTEIN CHOLESTEROL; NICOTINIC ACID; OMEGA 3 FATTY ACID; ROSUVASTATIN; SIMVASTATIN;

AMINOTRANSFERASE BLOOD LEVEL; ATHEROSCLEROSIS; CANCER INCIDENCE; CARDIOVASCULAR DISEASE; CHOLESTEROL BLOOD LEVEL; CLINICAL TRIAL; COMPARATIVE STUDY; CREATINE KINASE BLOOD LEVEL; DRUG EFFICACY; DRUG MEGADOSE; DRUG WITHDRAWAL; DYSLIPIDEMIA; EVIDENCE BASED MEDICINE; HEART INFARCTION; HEART MUSCLE REVASCULARIZATION; HUMAN; META ANALYSIS; MONOTHERAPY; MORTALITY; MYALGIA; OUTCOMES RESEARCH; PATIENT COMPLIANCE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; REVIEW; RHABDOMYOLYSIS; RISK REDUCTION; SIDE EFFECT; STROKE; SYSTEMATIC REVIEW; TOXIC HEPATITIS; TREATMENT OUTCOME; UNSPECIFIED SIDE EFFECT;

ANTICHOLESTEREMIC AGENTS; CARDIOVASCULAR DISEASES; CHOLESTEROL, HDL; CHOLESTEROL, LDL; DRUG THERAPY, COMBINATION; DYSLIPIDEMIAS; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; MEDICATION ADHERENCE; MORTALITY; RISK FACTORS;

EID: 70450211318     PISSN: 00034819     EISSN: 15393704     Source Type: Journal    
DOI: 10.7326/0003-4819-151-9-200911030-00144     Document Type: Review

References (120)

1. Miniño AM, Heron MP, Smith BL. Deaths: preliminary data for 2004. Natl Vital Stat Rep. 2006;54:1-49. [PMID: 16850709]
2. Mackay J, Mensah G. The Atlas of Heart Disease and Stroke. Geneva: World Health Organization; 2004.
3. Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, et al; 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. 2005;366:1267-1278 [PMID: 16214597]
4. Amarenco P, Bogousslavsky J, Callahan A 3rd, Goldstein LB, Hennerici M, Rudolph AE, et al; Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355:549-559 [PMID: 16899775]
5. Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr, Clark LT, Hunninghake DB, et al; National Heart, Lung, and Blood Institute. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004;110:227-239 [PMID: 15249516]
6. American Heart Association. Heart Disease and Stroke Statistics - 2008 Update. Dallas: Am Heart Assoc; 2008. Accessed at www.americanheart.org/ downloadable /heart/1200082005246HS-Stats%202008.final.pdf on 2 March 2009.
7. Garcia-Calvo M, Lisnock J, Bull HG, Hawes BE, Burnett DA, Braun MP, et al. The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1). Proc Natl Acad Sci U S A. 2005;102:8132-8137 [PMID: 15928087] (Pubitemid 40800055)
8. Shepherd J, Packard CJ, Patsch JR, Gotto AM Jr, Taunton OD. Effects of nicotinic acid therapy on plasma high density lipoprotein subfraction distribution and composition and on apolipoprotein A metabolism. J Clin Invest. 1979;63: 858-867 [PMID: 221531] (Pubitemid 9182535)
9. Sakai T, Kamanna VS, Kashyap ML. Niacin, but not gemfibrozil, selectively increases LP-AI, a cardioprotective subfraction of HDL, in patients with low HDL cholesterol. Arterioscler Thromb Vasc Biol. 2001;21:1783-1789 [PMID: 11701466] (Pubitemid 34219783)
10. Physicians' Desk Reference. 47th ed. Montvale, NJ: Medical Economics; 1993.
11. American Hospital Formulary Service (AHFS) Drug Information. Bethesda, MD: American Soc of Hospital Pharmacists; 1990.
12. U.S. Food and Drug Administration Centre for Drug Evaluation and Research. Approved Drug Products With Therapeutic Equivalence Evaluation (Orange Book). 12th ed. Washington, DC: U.S. Department of Health and Human Services; 1992.
13. Harris WS. ω-3 fatty acids and serum lipoproteins: human studies. Am J Clin Nutr. 1997;65:1645S-1654S. [PMID: 9129504]
14. Sharma M, Ansari M, Soares-Weiser K, Abou-setta A, Ooi T, Sears M, et al. Comparative Effectiveness of Lipid-Modifying Agents. AHRQ Evidence Report 09-EHC024-1. 2009. [Forthcoming]
15. Atkins D, Best D, Briss PA, Eccles M, Falck-Ytter Y, Flottorp S, et al; GRADE Working Group. Grading quality of evidence and strength of recommendations. BMJ. 2004;328:1490. [PMID: 15205295]
16. Feldman T, Koren M, InsullWJr, McKenney J, Schrott H, Lewin A, et al. Treatment of high-risk patients with ezetimibe plus simvastatin co-administration versus simvastatin alone to attain National Cholesterol Education Program Adult Treatment Panel III low-density lipoprotein cholesterol goals. Am J Cardiol. 2004;93:1481-1486 [PMID: 15194017] (Pubitemid 38749203)
17. Davidson MH, McGarry T, Bettis R, Melani L, Lipka LJ, LeBeaut AP, et al. Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia. J Am Coll Cardiol. 2002;40:2125-2134 [PMID: 12505224] (Pubitemid 36005898)
18. Goldberg AC, Sapre A, Liu J, Capece R, Mitchel YB; Ezetimibe Study Group. Efficacy and safety of ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia: a randomized, double-blind, placebocontrolled trial. Mayo Clin Proc. 2004;79:620-629 [PMID: 15132403] (Pubitemid 38580168)
19. Gaudiani LM, Lewin A, Meneghini L, Perevozskaya I, Plotkin D, Mitchel Y, et al. Efficacy and safety of ezetimibe co-administered with simvastatin in thiazolidinedione-treated type 2 diabetic patients. Diabetes Obes Metab. 2005;7: 88-97. [PMID: 15642080]
20. Bays HE, Ose L, Fraser N, Tribble DL, Quinto K, Reyes R, et al; Ezetimibe Study Group. A multicenter, randomized, double-blind, placebocontrolled, 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;26:1758-1773 [PMID: 15639688]
21. Dobs A, Guyton JR, McClusky D, Ponsonnet D, Melani L, Lebeaut A, et al; The Ezetemibe Study Group. Co-administration of ezetemibe with simvastatin [Abstract]. J Am Coll Cardiol. 2003;41:227A.
22. Conard SE, Bays HE, Leiter LA, Bird SR, Rubino J, Lowe RS, et al. Efficacy and safety of ezetimibe added on to atorvastatin (20 mg) versus uptitration of atorvastatin (to 40 mg) in hypercholesterolemic patients at moderately high risk for coronary heart disease. Am J Cardiol. 2008;102:1489-1494 [PMID: 19026302]
23. Hunninghake D, Insull W Jr, Toth P, Davidson D, Donovan JM, Burke SK. Coadministration of colesevelam hydrochloride with atorvastatin lowers LDL cholesterol additively. Atherosclerosis. 2001;158:407-416 [PMID: 11583720] (Pubitemid 32913651)
24. Durrington PN, Tuomilehto J, Hamann A, Kallend D, Smith K. Rosuvastatin and fenofibrate alone and in combination in type 2 diabetes patients with combined hyperlipidaemia. Diabetes Res Clin Pract. 2004;64:137-151 [PMID: 15063607] (Pubitemid 38456692)
25. Capuzzi DM, Morgan JM, Weiss RJ, Chitra RR, Hutchinson HG, Cressman MD. Beneficial effects of rosuvastatin alone and in combination with extended-release niacin in patients with a combined hyperlipidemia and low high-density lipoprotein cholesterol levels. Am J Cardiol. 2003;91:1304-1310 [PMID: 12767421]
26. Rodney RA, Sugimoto D, Wagman B, Zieve F, Kerzner B, Strony J, et al. Efficacy and safety of coadministration of ezetimibe and simvastatin in African- American patients with primary hypercholesterolemia. J Natl Med Assoc. 2006; 98:772-778 [PMID: 16749654]
27. Barrios V, Amabile N, Paganelli F, Chen JW, Allen C, Johnson-Levonas AO, 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;59:1377-1386 [PMID: 16351668] (Pubitemid 43922623)
28. Landray M, Baigent C, Leaper C, Adu D, Altmann P, Armitage J, et al. The second United Kingdom Heart and Renal Protection (UK-HARP-II) Study: a randomized controlled study of the biochemical safety and efficacy of adding ezetimibe to simvastatin as initial therapy among patients with CKD. Am J Kidney Dis. 2006;47:385-395 [PMID: 16490616] (Pubitemid 43255171)
29. Athyros VG, Mikhailidis DP, Papageorgiou AA, Didangelos TP, Peletidou A, Kleta D, et al. Targeting vascular risk in patients with metabolic syndrome but without diabetes. Metabolism. 2005;54:1065-1074 [PMID: 16092057] (Pubitemid 41033108)
30. Farnier M, Volpe M, Massaad R, Davies MJ, Allen C. Effect of coadministering ezetimibe with on-going simvastatin treatment on LDL-C goal attainment in hypercholesterolemic patients with coronary heart disease. Int J Cardiol. 2005;102:327-332 [PMID: 15982505] (Pubitemid 40854051)
31. Cruz-Fernández JM, Bedarida GV, Adgey J, Allen C, Johnson-Levonas AO, Massaad R. Efficacy and safety of ezetimibe co-administered with ongoing atorvastatin therapy in achieving low-density lipoprotein goal in patients with hypercholesterolemia and coronary heart disease. Int J Clin Pract. 2005;59:619-627 [PMID: 15924587] (Pubitemid 44192629)
32. Brohet C, Banai S, Alings AM, Massaad R, Davies MJ, Allen C. LDL-C goal attainment with the addition of ezetimibe to ongoing simvastatin treatment in coronary heart disease patients with hypercholesterolemia. Curr Med Res Opin. 2005;21:571-578 [PMID: 15899106] (Pubitemid 40676109)
33. Pearson TA, Denke MA, McBride PE, Battisti WP, Brady WE, Palmisano J. A community-based, randomized trial of ezetimibe added to statin therapy to attain NCEP ATP III goals for LDL cholesterol in hypercholesterolemic patients: the ezetimibe add-on to statin for effectiveness (EASE) trial. Mayo Clin Proc. 2005;80:587-595 [PMID: 15887425] (Pubitemid 40628813)
34. Ballantyne CM, Abate N, Yuan Z, King TR, Palmisano J. Dosecomparison study of the combination of ezetimibe and simvastatin (Vytorin) versus atorvastatin in patients with hypercholesterolemia: the Vytorin Versus Atorvastatin (VYVA) study. Am Heart J. 2005;149:464-473 [PMID: 15864235] (Pubitemid 40585409)
35. Geiss HC, Otto C, Hund-Wissner E, Parhofer KG. Effects of ezetimibe on plasma lipoproteins in severely hypercholesterolemic patients treated with regular LDL-apheresis and statins. Atherosclerosis. 2005;180:107-112 [PMID: 15823282] (Pubitemid 40501359)
36. Masana L, Mata P, Gagné C, Sirah W, Cho M, Johnson-Levonas AO, et al; Ezetimibe Study Group. Long-term safety and, tolerability profiles and lipidmodifying efficacy of ezetimibe coadministered with ongoing simvastatin treatment: a multicenter, randomized, double-blind, placebo-controlled, 48-week extension study. Clin Ther. 2005;27:174-184 [PMID: 15811480]
37. Grundy SM, Vega GL, Yuan Z, Battisti WP, Brady WE, Palmisano J. Effectiveness and tolerability of simvastatin plus fenofibrate for combined hyperlipidemia (the SAFARI trial). Am J Cardiol. 2005;95:462-468 [PMID: 15695129] (Pubitemid 40247539)
38. Ballantyne CM, Miller E, Chitra R. Efficacy and safety of rosuvastatin alone and in combination with cholestyramine in patients with severe hypercholesterolemia: a randomized, open-label, multicenter trial. Clin Ther. 2004;26:1855-1864 [PMID: 15639697] (Pubitemid 40089498)
39. Derosa G, Cicero AE, Bertone G, Piccinni MN, Ciccarelli L, Roggeri DE. Comparison of fluvastatin + fenofibrate combination therapy and fluvastatin monotherapy in the treatment of combined hyperlipidemia, type 2 diabetes mellitus, and coronary heart disease: a 12-month, randomized, double-blind, controlled trial. Clin Ther. 2004;26:1599-1607 [PMID: 15598476] (Pubitemid 39643020)
40. Taylor AJ, Sullenberger LE, Lee HJ, Lee JK, Grace KA. Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER) 2: a double-blind, placebo-controlled study of extended-release niacin on atherosclerosis progression in secondary prevention patients treated with statins. Circulation. 2004;110:3512-3517 [PMID: 15537681]
41. Stein E, Stender S, Mata P, Sager P, Ponsonnet D, Melani L, et al; Ezetimibe Study Group. Achieving lipoprotein goals in patients at high risk with severe hypercholesterolemia: efficacy and safety of ezetimibe co-administered with atorvastatin. Am Heart J. 2004;148:447-455 [PMID: 15389231]
42. Kosoglou T, Statkevich P, Yang B, Suresh R, Zhu Y, Boutros T, et al. Pharmacodynamic interaction between ezetimibe and rosuvastatin. Curr Med Res Opin. 2004;20:1185-1195 [PMID: 15324521]
43. Hong H, Xu ZM, Pang BS, Cui L, Wei Y, Guo WJ, et al. Effects of simvastain combined with omega-3 fatty acids on high sensitive C-reactive protein, lipidemia, and fibrinolysis in patients with mixed dyslipidemia. Chin Med Sci J. 2004;19:145-149 [PMID: 15250255] (Pubitemid 38901910)
44. Kosoglou T, Statkevich P, Meyer I, Cutler DL, Musiol B, Yang B, et al. Effects of ezetimibe on the pharmacodynamics and pharmacokinetics of lovastatin. Curr Med Res Opin. 2004;20:955-965 [PMID: 15200755] (Pubitemid 38821535)
45. Ballantyne CM, Blazing MA, King TR, Brady WE, Palmisano J. Efficacy and safety of ezetimibe co-administered with simvastatin compared with atorvastatin in adults with hypercholesterolemia. Am J Cardiol. 2004;93:1487-1494 [PMID: 15194018] (Pubitemid 38749204)
46. Insull W Jr, McGovern ME, Schrott H, Thompson P, Crouse JR, Zieve F, et al. Efficacy of extended-release niacin with lovastatin for hypercholesterolemia: assessing all reasonable doses with innovative surface graph analysis. Arch Intern Med. 2004;164:1121-1127 [PMID: 15159270] (Pubitemid 38668992)
47. Bays HE, Dujovne CA, McGovern ME, White TE, Kashyap ML, Hutcheson AG, et al; ADvicor Versus Other Cholesterol-Modulating Agents Trial Evaluation. 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]). Am J Cardiol. 2003;91:667-672 [PMID: 12633795]
48. Ballantyne CM, Houri J, Notarbartolo A, Melani L, Lipka LJ, Suresh R, et al; Ezetimibe Study Group. Effect of ezetimibe coadministered with atorvastatin in 628 patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. Circulation. 2003;107:2409-2415 [PMID: 12719279]
49. Melani L, Mills R, Hassman D, Lipetz R, Lipka L, LeBeaut A, et al; Ezetimibe Study Group. Efficacy and safety of ezetimibe coadministered with pravastatin in patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. Eur Heart J. 2003;24:717-728 [PMID: 12713766]
50. Hunninghake DB, McGovern ME, Koren M, Brazg R, Murdock D, Weiss S, et al. A dose-ranging study of a new, once-daily, dual-component drug product containing niacin extended-release and lovastatin. Clin Cardiol. 2003;26:112-118 [PMID: 12685616] (Pubitemid 36330859)
51. Kerzner B, Corbelli J, Sharp S, Lipka LJ, Melani L, LeBeaut A, et al; Ezetimibe Study Group. Efficacy and safety of ezetimibe coadministered with lovastatin in primary hypercholesterolemia. Am J Cardiol. 2003;91:418-424 [PMID: 12586255] (Pubitemid 36183559)
52. Kosoglou T, Meyer I, Veltri EP, Statkevich P, Yang B, Zhu Y, et al. Pharmacodynamic interaction between the new selective cholesterol absorption inhibitor ezetimibe and simvastatin. Br J Clin Pharmacol. 2002;54:309-319 [PMID: 12236852] (Pubitemid 35056576)
53. Athyros VG, Papageorgiou AA, Athyrou VV, Demitriadis DS, Kontopoulos AG. Atorvastatin and micronized fenofibrate alone and in combination in type 2 diabetes with combined hyperlipidemia. Diabetes Care. 2002;25:1198-1202 [PMID: 12087019]
54. Chan DC, Watts GF, Mori TA, Barrett PH, Beilin LJ, Redgrave TG. Factorial study of the effects of atorvastatin and fish oil on dyslipidaemia in visceral obesity. Eur J Clin Invest. 2002;32:429-436 [PMID: 12059988]
55. 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. 2002;105:2469-2475 [PMID: 12034651] (Pubitemid 34568966)
56. Athyros VG, Papageorgiou AA, Athyrou VV, Demitriadis DS, Pehlivanidis AN, Kontopoulos AG. Atorvastatin versus four statin-fibrate combinations in patients with familial combined hyperlipidaemia. J Cardiovasc Risk. 2002;9:33-39 [PMID: 11984215]
57. Davidson MH, Toth P, Weiss S, McKenney J, Hunninghake D, Isaacsohn J, et al. Low-dose combination therapy with colesevelam hydrochloride and lovastatin effectively decreases low-density lipoprotein cholesterol in patients with primary hypercholesterolemia. Clin Cardiol. 2001;24:467-474 [PMID: 11403509] (Pubitemid 32520218)
58. Nordøy A, Hansen JB, Brox J, Svensson B. Effects of atorvastatin and omega-3 fatty acids on LDL subfractions and postprandial hyperlipemia in patients with combined hyperlipemia. Nutr Metab Cardiovasc Dis. 2001;11:7-16. [PMID: 11383326] (Pubitemid 33687789)
59. Durrington PN, Bhatnagar D, Mackness MI, Morgan J, Julier K, Khan MA, et al. An omega-3 polyunsaturated fatty acid concentrate administered for one year decreased triglycerides in simvastatin treated patients with coronary heart disease and persisting hypertriglyceridaemia. Heart. 2001;85:544-548 [PMID: 11303007] (Pubitemid 32973499)
60. Knapp HH, Schrott H, Ma P, Knopp R, Chin B, Gaziano JM, et al. Efficacy and safety of combination simvastatin and colesevelam in patients with primary hypercholesterolemia. Am J Med. 2001;110:352-360 [PMID: 11286949] (Pubitemid 32248724)
61. Simons LA. Comparison of atorvastatin alone versus simvastatin +/- cholestyramine in the management of severe primary hypercholesterolaemia (the six cities study). Aust N Z J Med. 1998;28:327-333 [PMID: 9673745]
62. Eriksson M, Hådell K, Holme I, Walldius G, Kjellström T. Compliance with and efficacy of treatment with pravastatin and cholestyramine: a randomized study on lipid-lowering in primary care. J Intern Med. 1998;243:373-380 [PMID: 9651560] (Pubitemid 28255482)
63. Nordøy A, Bønaa KH, Nilsen H, Berge RK, Hansen JB, Ingebretsen OC. Effects of Simvastatin and omega-3 fatty acids on plasma lipoproteins and lipid peroxidation in patients with combined hyperlipidaemia. J Intern Med. 1998; 243:163-170 [PMID: 9566646] (Pubitemid 28156665)
64. Ito MK, Shabetai R. Pravastatin alone and in combination with low-dose cholestyramine in patients with primary hypercholesterolemia and coronary artery disease. Am J Cardiol. 1997;80:799-802. [PMID: 9315597] (Pubitemid 27413600)
65. Davidson MH, Macariola-Coad JR, McDonald AM, Maki KC, Hall HA. Separate and joint effects of marine oil and simvastatin in patients with combined hyperlipidemia. Am J Cardiol. 1997;80:797-798 [PMID: 9315596]
66. Gardner SF, Schneider EF, Granberry MC, Carter IR. Combination therapy with low-dose lovastatin and niacin is as effective as higher-dose lovastatin. Pharmacotherapy. 1996;16:419-423 [PMID: 8726600]
67. O'Keefe JH Jr, Harris WS, Nelson J, Windsor SL. Effects of pravastatin with niacin or magnesium on lipid levels and postprandial lipemia. Am J Cardiol. 1995;76:480-484 [PMID: 7653448]
68. Vacek JL, Dittmeier G, Chiarelli T, White J, Bell HH. Comparison of lovastatin (20 mg) and nicotinic acid (1.2 g) with either drug alone for type II hyperlipoproteinemia. Am J Cardiol. 1995;76:182-184 [PMID: 7611158]
69. Smit JW, Jansen GH, de Bruin TW, Erkelens DW. Treatment of combined hyperlipidemia with fluvastatin and gemfibrozil, alone or in combination, does not induce muscle damage. Am J Cardiol. 1995;76:126A-128A. [PMID: 7604787]
70. Schrott HG, Stein EA, Dujovne CA, Davidson MH, Goris GB, Oliphant TH, et al. Enhanced low-density lipoprotein cholesterol reduction and costeffectiveness by low-dose colestipol plus lovastatin combination therapy. Am J Cardiol. 1995;75:34-39 [PMID: 7801861]
71. Sprecher DL, Abrams J, Allen JW, Keane WF, Chrysant SG, Ginsberg H, et al. Low-dose combined therapy with fluvastatin and cholestyramine in hyperlipidemic patients. Ann Intern Med. 1994;120:537-543 [PMID: 8093139] (Pubitemid 24091593)
72. Comparative efficacy and safety of pravastatin and cholestyramine alone and combined in patients with hypercholesterolemia. Pravastatin Multicenter Study Group II. Arch Intern Med. 1993;153:1321-1329 [PMID: 8507122]
73. Wiklund O, Angelin B, Bergman M, Berglund L, Bondjers G, Carlsson A, et al. Pravastatin and gemfibrozil alone and in combination for the treatment of hypercholesterolemia. Am J Med. 1993;94:13-20. [PMID: 8420296] (Pubitemid 23021166)
74. Simons LA, Simons J, Parfitt A. Successful management of primary hypercholesterolaemia with simvastatin and low-dose colestipol. Med J Aust. 1992; 157:455-459 [PMID: 1406395]
75. Ismail F, Corder CN, Epstein S, Barbi G, Thomas S. Effects of pravastatin and cholestyramine on circulating levels of parathyroid hormone and vitamin D metabolites. Clin Ther. 1990;12:427-430 [PMID: 2125243]
76. O'Brien RC, Simons LA, Clifton P, Cooper ME, Jennings GL, Jerums G, et al. Comparison of simvastatin and cholestyramine in the treatment of primary hypercholesterolaemia. Med J Aust. 1990;152:480-483 [PMID: 2199801] (Pubitemid 20143571)
77. Liu M, Wallmon A, Wallin R, Saldeen T. Effects of stable fish oil and simvastatin on plasma lipoproteins in patients with hyperlipidemia. Nutr Res. 2003;23:1027-1034 (Pubitemid 36936210)
78. Barbi G, Corder CN, Koren E, McConathy W, Ye SQ, Wilson P. Effect of pravastatin and cholestyramine on triglyceride-rich lipoprotein particles and Lp(a) in patients with type II hypercholesterolemia. Drug Dev Res. 1992;27:297-306.
79. Johansson J. Low-dose combination therapy with colestipol and simvastatin in patients with moderate to severe hypercholesterolaemia. Nutr Metab Cardiovasc Dis. 1995;5:39-44.
80. McKenney JM, Jones PH, Bays HE, Knopp RH, Kashyap ML, Ruoff GE, et al. Comparative effects on lipid levels of combination therapy with a statin and extended-release niacin or ezetimibe versus a statin alone (the COMPELL study). Atherosclerosis. 2007;192:432-437 [PMID: 17239888]
81. Blagden MD, Chipperfield R. Efficacy and safety of ezetimibe coadministered with atorvastatin in untreated patients with primary hypercholesterolaemia and coronary heart disease. Curr Med Res Opin. 2007;23:767-775 [PMID: 17407633] (Pubitemid 46631480)
82. Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, et al; Japan EPA lipid intervention study (JELIS) Investigators. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007;369: 1090-1098 [PMID: 17398308]
83. Ballantyne CM, Weiss R, Moccetti T, Vogt A, Eber B, Sosef F, et al; EXPLORER Study Investigators. Efficacy and safety of rosuvastatin 40 mg alone or in combination with ezetimibe in patients at high risk of cardiovascular disease (results from the EXPLORER study). Am J Cardiol. 2007;99:673-680 [PMID: 17317370] (Pubitemid 46273307)
84. Patel JV, Hughes EA. Efficacy, safety and LDL-C goal attainment of ezetimibe 10 mg-simvastatin 20 mg vs. placebo-simvastatin 20 mg in UK-based adults with coronary heart disease and hypercholesterolaemia. Int J Clin Pract. 2006;60:914-921 [PMID: 16893434]
85. Piorkowski M, Fischer S, Stellbaum C, Jaster M, Martus P, Morguet AJ, et al. Treatment with ezetimibe plus low-dose atorvastatin compared with higherdose atorvastatin alone: is sufficient cholesterol-lowering enough to inhibit platelets? J Am Coll Cardiol. 2007;49:1035-1042 [PMID: 17349882]
86. Goldberg RB, Guyton JR, Mazzone T, Weinstock RS, Polis A, Edwards P, et al. Ezetimibe/simvastatin vs atorvastatin in patients with type 2 diabetes mellitus and hypercholesterolemia: the VYTAL study. Mayo Clin Proc. 2006;81: 1579-1588 [PMID: 17165637] (Pubitemid 44871902)
87. Berthold HK, Naini A, Di Mauro S, Hallikainen M, Gylling H, Krone W, et al. Effect of ezetimibe and/or simvastatin on coenzyme Q10 levels in plasma: a randomised trial. Drug Saf. 2006;29:703-712 [PMID: 16872244] (Pubitemid 44175041)
88. Catapano AL, Davidson MH, Ballantyne CM, Brady WE, Gazzara RA, Tomassini JE, et al. Lipid-altering efficacy of the ezetimibe/simvastatin single tablet versus rosuvastatin in hypercholesterolemic patients. Curr Med Res Opin. 2006;22:2041-2053 [PMID: 17022864]
89. Muhlestein JB, May HT, Jensen JR, Horne BD, Lanman RB, Lavasani F, et al. The reduction of inflammatory biomarkers by statin, fibrate, and combination therapy among diabetic patients with mixed dyslipidemia: the DIACOR (Diabetes and Combined Lipid Therapy Regimen) study. J Am Coll Cardiol. 2006;48:396-401. [PMID: 16843192]
90. Davidson MH, Stein EA, Bays HE, Maki KC, Doyle RT, Shalwitz RA, et al; COMBination of prescription Omega-3 with Simvastatin (COMBOS) Investigators. Efficacy and tolerability of adding prescription omega-3 fatty acids 4 g/d to simvastatin 40 mg/d in hypertriglyceridemic patients: an 8-week, randomized, double-blind, placebo-controlled study. Clin Ther. 2007;29:1354-1367 [PMID: 17825687]
91. Chenot F, Montant PF, Marcovitch O, Blaimont M, de Meester A, Descamps OS. Co-administration of ezetimibe and simvastatin in acute myocardial infarction. Eur J Clin Invest. 2007;37:357-363 [PMID: 17461981] (Pubitemid 46656104)
92. Meyer BJ, Hammervold T, Rustan AC, Howe PR. Dose-dependent effects of docosahexaenoic acid supplementation on blood lipids in statin-treated hyperlipidaemic subjects. Lipids. 2007;42:109-115 [PMID: 17393216] (Pubitemid 351912041)
93. Shankar PK, Bhat R, Prabhu M, Reddy BP, 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. J Clin Lipidol. 2007;1:264-270 (Pubitemid 47354995)
94. Shah HD, Parikh KH, Chag MC, Shah UG, Baxi HA, Chandarana AH, et al. Beneficial effects of the addition of fenofibrate to statin therapy in patients with acute coronary syndrome after percutaneous coronary interventions. Exp Clin Cardiol. 2007;12:91-96 [PMID: 18650989]
95. Constance C, Westphal S, Chung N, Lund M, McCrary Sisk C, Johnson- Levonas AO, et al. Efficacy of ezetimibe/simvastatin 10/20 and 10/40 mg compared with atorvastatin 20 mg in patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2007;9:575-584 [PMID: 17451425] (Pubitemid 47018521)
96. Kuvin JT, Dave DM, Sliney KA, Mooney P, Patel AR, Kimmelstiel CD, et al. Effects of extended-release niacin on lipoprotein particle size, distribution, and inflammatory markers in patients with coronary artery disease. Am J Cardiol. 2006;98:743-745 [PMID: 16950175] (Pubitemid 44301006)
97. Isaacsohn JL, Bakker-Arkema RG, Fayyad R, Whitcomb R, Black DM. Atorvastatin, a new HMG-CoA reductase inhibitor, does not affect glucocorticoid hormones in patients with hypercholesterolemia. J Cardiovasc Pharmacol Ther. 1997;2:243-249 [PMID: 10684465] (Pubitemid 27469364)
98. Napoli C, Lepore S, Chiariello P, Condorelli M, Chiariello M. Long-term treatment with pravastatin alone and in combination with gemfibrozil in familial type iib hyperlipoproteinemia or combined hyperlipidemia. J Cardiovasc Pharmacol Ther. 1997;2:17-26. [PMID: 10684438] (Pubitemid 27157109)
99. Kastelein JJ, Akdim F, Stroes ES, Zwinderman AH, Bots ML, Stalenhoef AF, et al; ENHANCE Investigators. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med. 2008;358:1431-1443 [PMID: 18376000]
100. Stein EA, Davidson MH, Dujovne CA, Hunninghake DB, Goldberg RB, Illingworth DR, et al. Efficacy and tolerability of low-dose simvastatin and niacin, alone and in combination, in patients with combined hyperlipidemia: a prospective trial. J Cardiovasc Pharmacol Ther. 1996;1:107-116 [PMID: 10684407]
101. Stein EA, Ballantyne CM, Windler E, Sirnes PA, Sussekov A, Yigit Z, et al. Efficacy and tolerability of fluvastatin XL 80 mg alone, ezetimibe alone, and the combination of fluvastatin XL 80 mg with ezetimibe in patients with a history of muscle-related side effects with other statins. Am J Cardiol. 2008;101:490-496 [PMID: 18312764] (Pubitemid 351199443)
102. Heinonen TM, Schrott H, McKenney JM, Sniderman AD, Broyles FE, Zavoral JH, et al. Atorvastatin, a new HMG-CoA reductase inhibitor as monotherapy and combined with colestipol. J Cardiovasc Pharmacol Ther. 1996;1: 117-122 [PMID: 10684408]
103. Evaluation of the safety and efficacy of Advicor (a combination tablet of niacin extended-release/lovastatin immediate-release): a dose response study. FDA-Advicor (MA-14). Silver Spring, MD: U.S. Food and Drug Administration; 2008.
104. Evaluation of the safety and efficacy of Advicor (a combination tablet of niacin extended-release/lovastatin immediate-release): a dose ranging study. FDAAdvicor (M-06). Silver Spring, MD: U.S. Food and Drug Administration; 2008.
105. Dagli N, Yavuzkir M, Karaca I. The effects of high dose pravastatin and low dose pravastatin and ezetimibe combination therapy on lipid, glucose metabolism and inflammation. Inflammation. 2007;30:230-235 [PMID: 17687635] (Pubitemid 350264457)
106. Reckless JP, Henry P, Pomykaj T, Lim ST, Massaad R, Vandormael K, 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;62:539-554 [PMID: 18266852] (Pubitemid 351348028)
107. 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;101:1428-1436 [PMID: 18471454]
108. Roeters van Lennep HW, Liem AH, Dunselman PH, 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;24:685-694 [PMID: 18226326]
109. Gouni-Berthold I, Berthold HK, Gylling H, Hallikainen M, Giannakidou E, Stier S, et al. Effects of ezetimibe and/or simvastatin on LDL receptor protein expression and on LDL receptor and HMG-CoA reductase gene expression: a randomized trial in healthy men. Atherosclerosis. 2008;198:198-207. [PMID: 17980884]
110. Moore A, Phan BA, Challender C, Williamson J, Marcovina S, Zhao XQ. Effects of adding extended-release niacin and colesevelam to statin therapy on lipid levels in subjects with atherosclerotic disease. J Clin Lipidol. 2007;1:620-625 (Pubitemid 350215509)
111. Ballantyne CM, Davidson MH, McKenney J. Comparison of the safety and efficacy of a combination tablet of niacin extended release and simvastatin with simvastatin 80 mg monotherapy: the SEACOAST II (high-dose) study. J Clin Lipidol. 2008;2:79-90.
112. Leiter LA, Bays H, Conard S, Bird S, Rubino J, Hanson ME, et al. Efficacy and safety of ezetimibe added on to atorvastatin (40 mg) compared with uptitration of atorvastatin (to 80 mg) in hypercholesterolemic patients at high risk of coronary heart disease. Am J Cardiol. 2008;102:1495-1501 [PMID: 19026303]
113. Airan-Javia SL, Wolf RL, Wolfe ML, Tadesse M, Mohler E, Reilly MP. Atheroprotective lipoprotein effects of a niacin-simvastatin combination compared to low- and high-dose simvastatin monotherapy. Am Heart J. 2009;157: 687.e1-8 [PMID: 19332196]
114. van Dam M, Kastelein J. Efficacy and tolerability of fluvastatin in a titration dosage regimen in hyperlipidaemic patients: results of a multicentre phase IV study. Clin Drug Investig. 2001;21:477-484 (Pubitemid 32681919)
115. Ojala JP, Helve E, Karjalainen K, Tarkkanen A, Tikkanen MJ. Long-term maintenance of therapeutic response to lovastatin in patients with familial and non-familial hypercholesterolemia: a 3-year follow-up. Atherosclerosis. 1990;82: 85-95. [PMID: 2360923] (Pubitemid 20170545)
116. Mol MJ, Stuyt PM, Demacker PN, Stalenhoef AF. The effects of simvastatin on serum lipoproteins in severe hypercholesterolaemia. Neth J Med. 1990; 36:182-190 [PMID: 2355995]
117. Türk TR, Voropaeva E, Kohnle M, Nürnberger J, Philipp T, Kribben A, et al. Ezetimibe treatment in hypercholesterolemic kidney transplant patients is safe and effective and reduces the decline of renal allograft function: a pilot study. Nephrol Dial Transplant. 2008;23:369-373 [PMID: 17956887] (Pubitemid 351767400)
118. Josan K, Majumdar SR, McAlister FA. The efficacy and safety of intensive statin therapy: a meta-analysis of randomized trials. CMAJ. 2008;178:576-584 [PMID: 18299547]
119. Brown BG, Taylor AJ. Does ENHANCE diminish confidence in lowering LDL or in ezetimibe? [Editorial]. N Engl J Med. 2008;358:1504-1507 [PMID: 18376002]
120. Sokol MC, McGuigan KA, Verbrugge RR, Epstein RS. Impact of medication adherence on hospitalization risk and healthcare cost. Med Care. 2005;43: 521-530 [PMID: 15908846]