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Medwave 2016;16(Suppl5):e6632 doi: 10.5867/medwave.2016.6632
¿Disminuye el riesgo cardiovascular al agregar ezetimibe al tratamiento con estatinas?
Does the addition of ezetimibe to statins reduce cardiovascular risk?
Francisca I Araya, Bruno Grassi
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Abstract

Statins are the mainstay of lipid-lowering therapy nowadays, since they reduce cardiovascular risk when used as primary or secondary prevention. However, only one third of the patients reach the goals established in several guidelines, and even if they do, they keep a risk higher than healthy controls. One of the new lipid-lowering agents is ezetimibe. Searching in Epistemonikos database, which is maintained by screening multiple databases, we identified nine systematic reviews comprising 67 trials overall. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded adding ezetimibe to statins probably results in little or no difference in overall mortality. It might lead to a small reduction in the risk of myocardial infarction and stroke, but the certainty of the evidence is low.


 
Problem

Cardiovascular disease is the leading cause of death in adults. Higher LDL cholesterol levels are associated to an increase in the risk of coronary artery disease. This risk decreases with lower LDL levels until approximately 80 mg/dl (2.1 mmol/l) [1]. Therefore, multiple clinical guidelines have set LDL goals, which in many cases require intensive treatment [1]. Even though high dose statin regimen constitutes an option, many patients do not achieve the goals. In addition, even when they do, their cardiovascular risk remains higher than the general population, an effect called residual risk. New alternatives have emerged, such as ezetimibe, a cholesterol absorption inhibitor that blocks the intestinal absorption of dietary and biliary cholesterol and related plant sterols without affecting the uptake of triglycerides or fat-soluble vitamins. Considering its mechanism differs from statins, which reduce cholesterol synthesis, they might be a good choice for combination treatment. However, it remains unclear if adding ezetimibe to statin treatment has benefits, especially in reducing long-term cardiovascular risk.

Methods

We used Epistemonikos database, which is maintained by screening multiple databases, to identify systematic reviews and their included primary studies. With this information, we generated a structured summary using a pre-established format, which includes key messages, a summary of the body of evidence (presented as an evidence matrix in Epistemonikos), meta-analysis of the total of studies, a summary of findings table following the GRADE approach and a table of other considerations for decision-making.

Key messages

  • The addition of ezetimibe to statins probably leads to little or no difference in overall mortality.
  • The addition of ezetimibe to statins might lead to a small reduction in the risk of myocardial infarction and stroke, but the certainty of the evidence is low.
  • The addition of ezetimibe to statins does not increase serious adverse events. 
About the body of evidence for this question

What is the evidence.
See evidence matrix  in Epistemonikos later

We found nine systematic reviews [2], [3], [4], [5],
[6], [7], [8], [9], [10] that include 67 randomized controlled trials on ezetimibe and hypercholesterolemia, reported in 69 references [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55],
[56], [57], [58], [59], [60], [61], [62], [63], [64], [65], [66], [67], [68], [69], [70], [71], [72], [73], [74], [75], [76], [77], [78], [79]. This summary analyzes the 37 trials that compared the addition of ezetimibe to statins versus same dose of statins used as monotherapy, which constitutes the most relevant clinical question [12], [17], [18], [19], [23], [24], [26], [27], [28], [29], [31], [34], [35], [36], [37], [40], [42], [43], [46], [48], [49], [50], [52], [53], [54], [58], [65], [66], [67], [68], [69], [71], [73], [74], [76], [77], [78].

What types of patients were included

Nine trials included patients with coronary artery disease [26], [27], [37], [42], [48], [53], [54], [71], [74]; two of them included participants with LDL levels below 160 mg/dl [42],[71]. One trial included patients with hypercholesterolemia and high cardiovascular risk [58], one trial was conducted on patients with acute coronary syndrome [29], one trial on patients with acute myocardial infarction [69], one trial included diabetic patients with hypercholesterolemia [17], two trials included patients with peripheral artery disease [50], [76]; two trials included patients with chronic kidney disease [31], [73] and 18 trials included patients with primary hypercholesterolemia [12], [18], [19], [23], [24], [28], [34], [35], [36], [40], [43], [46], [65], [66], [67], [68], [77], [78]. One trial included African-American participants only [18]. One trial included homozygous familial hypercholesterolemia [52]; and one trial was conducted on healthy subjects [49].

What types of interventions were included

Five trials compared the effects of atorvastatin and ezetimibe versus atorvastatin plus placebo [26], [42], [66], [67], [74]; 22 trials simvastatin plus ezetimibe versus simvastatin plus placebo [17], [18], [19], [23], [28], [29], [31], [35], [37], [40], [43], [46], [49], [53], [54], [68], [69], [71], [73], [76], [77], [78]; one trial atorvastatin and simvastatin associated with ezetimibe versus both statins plus placebo separately [52]; one trial simvastatin plus ezetimibe versus atorvastatin plus placebo [65]; six trials compared pravastatin, lovastatin, fluvastatin or several statins in the same trial associated with ezetimibe versus statin monotherapy [12], [24], [34], [36], [48], [58]; and two trials compared rosuvastatin plus ezetimibe versus rosuvastatin plus placebo [27], [50]. 

What types of outcomes
were measured

Even though the primary studies reported outcomes in different ways, the systematic reviews identified grouped them as follows:

  • Overall mortality
  • Cardiovascular mortality
  • Cardiovascular events (nonfatal acute myocardial infarction, nonfatal stroke, high risk unstable angina and coronary revascularization)
  • Acute myocardial infarction
  • Stroke
  • Coronary revascularization
  • Serious adverse events (life threatening events, events that require hospitalization, congenital anomalies or permanent damage)
  • Cancer incidence
Summary of findings

The information about the effects of ezetimibe associated to statins is based on 37 randomized controlled trials [12], [17], [18], [19], [23], [24], [26], [27], [28], [29], [31], [34], [35], [36], [37], [40], [42], [43], [46], [48], [49], [50], [52], [53], [54], [58], [65], [66],[67], [68], [69], [71], [73], [74], [76], [77], [78]. Only nine trials reported overall mortality [29], [31], [42], [43], [50], [66], [73], [74], [76], seven reported nonfatal myocardial infarction [27], [29], [43], [50], [73], [74], [76], six informed nonfatal stroke [31], [43], [50], [73], [74], [76], three reported coronary revascularization [27], [29], [74] and 17 analyzed serious adverse events [17], [23], [24], [27], [29], [30], [31], [37], [42], [46], [53], [54], [64], [66], [71], [73], [78]. The summary of findings is the following:

  • The addition of ezetimibe to statins probably leads to little or no difference in overall mortality. The certainty of the evidence is moderate.
  • The addition of ezetimibe to statins might lead to a small reduction in the risk of myocardial infarction, but the certainty of the evidence is low.
  • The addition of ezetimibe to statins might lead to a small reduction in the risk of stroke, but the certainty of the evidence is low.
  • The addition of ezetimibe to statins does not increase serious adverse events. The certainty of the evidence is high. 

Other considerations for decision-making

To whom this evidence does and does not apply
  • Most data comes from trials with patients with LDL levels ≤ 140 mg/dl, with chronic kidney disease or with recent acute coronary syndrome.
  • It is reasonable to expect a similar effect in patients with a lower cardiovascular risk, however, would ezetimibe effect be true, the benefits on these patients would be even less, due to their lower baseline risk. 
About the outcomes included in this summary
  • The outcomes included are those most relevant for decision making.
  • It is important to note the LDL cholesterol level achieved is not a patient reported outcome, but a surrogate outcome. These results must be used only when there is no information on more important outcomes available.
  • Other outcome commonly used by the main guidelines is revascularization. This was not included because of its minor relative importance when being compared to the others. However, no effect on this outcome was observed (RR 0.96; 95% CI 0.90 to 1.01; high certainty of the evidence).
Balance between benefits and risks, and certainty of the evidence
  • This treatment probably has no effect on mortality, and it might have a small effect on cardiovascular events, but this is based on low-certainty evidence. On the other hand, it has no serious adverse effects. 
What would patients and their doctors think about this intervention
  • Given this intervention has a small and uncertain benefit, but without any adverse effects, and at a relatively high cost, there will probably be a high degree of variability in the decisions made by patients and their physicians, depending on how they value these factors.
Resource considerations
  • Considering ezetimibe is a high cost drug and has a small magnitude of benefit, it is unlikely that it is a cost effective alternative, although a formal evaluation on this matter would be desirable on settings where its use is being considered.

Differences between this summary and other sources
  • This summary partially agrees with the different systematic reviews, who differ between themselves. For example, one of the reviews concludes that even with a small effect, because of the importance of the outcomes analyzed, these must be important to patients [3], meanwhile others suggest there is no relevant benefit in comparison to statins as a monotherapy [5].
  • The 2015 European Society of Cardiology guidelines recommend the use of ezetimibe in patients with LDL levels above ≥70mg/dl despite maximally tolerated dose of statin therapy [80]. This recommendation does not differ from this summary, as it recommends ezetimibe exclusively if statin treatment fails, acknowledging the small reduction in cardiovascular events and the scant difference in mortality. 
Could this evidence change in the future?
  • The probability of future evidence changing the conclusions of this summary for some of the outcomes that are critical for decision making is high, because of the level of uncertainty.
How we conducted this summary

Using automated and collaborative means, we compiled all the relevant evidence for the question of interest and we present it as a matrix of evidence.


Follow the link to access the interactive version: Ezetimibe for hypercholesterolaemia

Notes

The upper portion of the matrix of evidence will display a warning of “new evidence” if new systematic reviews are published after the publication of this summary. Even though the project considers the periodical update of these summaries, users are invited to comment in Medwave or to contact the authors through email if they find new evidence and the summary should be updated earlier. After creating an account in Epistemonikos, users will be able to save the matrixes and to receive automated notifications any time new evidence potentially relevant for the question appears.

The details about the methods used to produce these summaries are described here http://dx.doi.org/10.5867/medwave.2014.06.5997.

Epistemonikos foundation is a non-for-profit organization aiming to bring information closer to health decision-makers with technology. Its main development is Epistemonikos database (www.epistemonikos.org).

These summaries follow a rigorous process of internal peer review.

Conflicts of interest
The authors do not have relevant interests to declare.

Licencia Creative Commons Esta obra de Medwave está bajo una licencia Creative Commons Atribución-NoComercial 3.0 Unported. Esta licencia permite el uso, distribución y reproducción del artículo en cualquier medio, siempre y cuando se otorgue el crédito correspondiente al autor del artículo y al medio en que se publica, en este caso, Medwave.

 

Statins are the mainstay of lipid-lowering therapy nowadays, since they reduce cardiovascular risk when used as primary or secondary prevention. However, only one third of the patients reach the goals established in several guidelines, and even if they do, they keep a risk higher than healthy controls. One of the new lipid-lowering agents is ezetimibe. Searching in Epistemonikos database, which is maintained by screening multiple databases, we identified nine systematic reviews comprising 67 trials overall. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded adding ezetimibe to statins probably results in little or no difference in overall mortality. It might lead to a small reduction in the risk of myocardial infarction and stroke, but the certainty of the evidence is low.

Autores: Francisca I Araya[1], Bruno Grassi[1,2]

Filiación:
[1] Proyecto Epistemonikos, Santiago, Chile
[2] Departamento de Nutrición y Diabetes, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile

E-mail: bagrassi@gmail.com

Correspondencia a:
[1] Facultad de Medicina
Pontificia Universidad Católica de Chile
Diagonal Paraguay 476
Santiago Centro
Chile

Citación: Araya FI, Grassi B. Does the addition of ezetimibe to statins reduce cardiovascular risk?. Medwave 2016;16(Suppl5):e6632 doi: 10.5867/medwave.2016.6632

Fecha de publicación: 5/12/2016

Ficha PubMed

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  1. Chan DK, O'Rourke F, Shen Q, Mak JC, Hung WT. Meta-analysis of the cardiovascular benefits of intensive lipid lowering with statins. Acta Neurol Scand. 2011 Sep;124(3):188-95. | CrossRef | PubMed |
  2. Sharma M, Ansari MT, Abou-Setta AM, Soares-Weiser K, Ooi TC, Sears M, et al. Systematic review: comparative effectiveness and harms of combination therapy and monotherapy for dyslipidemia. Ann Intern Med. 2009 Nov 3;151(9):622-30. | CrossRef | PubMed |
  3. Nußbaumer B, Glechner A, Kaminski-Hartenthaler A, Mahlknecht P, Gartlehner G. Ezetimibe-Statin Combination Therapy. Dtsch Arztebl Int. 2016 Jul 1;113(26):445-53 | CrossRef | PubMed |
  4. Pandor A, Ara RM, Tumur I, Wilkinson AJ, Paisley S, Duenas A, et al. Ezetimibe monotherapy for cholesterol lowering in 2,722 people: systematic review and meta-analysis of randomized controlled trials. J Intern Med. 2009 May;265(5):568-80. | CrossRef | PubMed |
  5. Battaggia A, Donzelli A, Font M, Molteni D, Galvano A. Clinical efficacy and safety of Ezetimibe on major cardiovascular endpoints: systematic review and meta-analysis of randomized controlled trials. PLoS One. 2015 Apr 27;10(4):e0124587 | CrossRef | PubMed |
  6. 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. 2007 Aug;23(8):2009-26 | PubMed |
  7. Santee J, Lindsey C, Pace H. Relative efficacy of antilipemic agents in non–high-density lipoprotein cholesterol reduction. J Pharm Pract. 2012 Aug;25(4):447-56 | PubMed |
  8. Mikhailidis DP, Lawson RW, McCormick AL, Sibbring GC, Tershakovec AM, Davies GM, et al. Comparative efficacy of the addition of ezetimibe to statin vs statin titration in patients with hypercholesterolaemia: systematic review and meta-analysis. Curr Med Res Opin. 2011 Jun;27(6):1191-210 | CrossRef | PubMed |
  9. Ambegaonkar BM, Tipping D, Polis AB, Tomassini JE, Tershakovec AM. Achieving goal lipid levels with ezetimibe plus statin add-on or switch therapy compared with doubling the statin dose. A pooled analysis. Atherosclerosis. 2014 Dec;237(2):829-37. | CrossRef | PubMed |
  10. Ara R, Tumur I, Pandor A, Duenas A, Williams R, Wilkinson A, et al. Ezetimibe for the treatment of hypercholesterolaemia: a systematic review and economic evaluation. Health Technol Assess. 2008 May;12(21):iii, xi-xiii, 1-212 | PubMed |
  11. Zieve F, Wenger NK, Ben-Yehuda O, Constance C, Bird S, Lee R, et al. Safety and efficacy of ezetimibe added to atorvastatin versus up titration of atorvastatin to 40 mg in Patients > or = 65 years of age (from the ZETia in the ELDerly [ZETELD] study). Am J Cardiol. 2010 Mar 1;105(5):656-63 | CrossRef | PubMed |
  12. 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 May;80(5):587-95 | PubMed |
  13. Strony J, Yang B, Hanson ME, Veltri EP. Long-term safety and tolerability of ezetimibe coadministered with simvastatin in hypercholesterolemic patients: a randomized, 12-month double-blind extension study. Curr Med Res Opin. 2008 Nov;24(11):3149-57 | CrossRef | PubMed |
  14. Stein E, Stender S, Mata P, Sager P, Ponsonnet D, Melani L, et al. Achieving lipoprotein goals in patients at high risk with severe hypercholesterolemia: efficacy and safety of ezetimibe co-administered with atorvastatin. Am Heart J. 2004 Sep;148(3):447-55. | PubMed |
  15. 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 Dec 1;102(11):1489-94 | CrossRef | PubMed |
  16. Knopp RH, Gitter H, Truitt T, Bays H, Manion CV, Lipka LJ, et al. Effects of ezetimibe, a new cholesterol absorption inhibitor, on plasma lipids in patients with primary hypercholesterolemia. Eur Heart J. 2003 Apr;24(8):729-41 | PubMed |
  17. 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 Dec;81(12):1579-88. Erratum in: Mayo Clin Proc. 2007 Mar;82(3):387 | PubMed |
  18. 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 May;98(5):772-8 | PubMed |
  19. 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 Aug;1(4):264-70 | CrossRef | PubMed |
  20. Hing Ling PK, Civeira F, Dan AG, Hanson ME, Massaad R, De Tilleghem Cle B, et al. Ezetimibe/simvastatin 10/40 mg versus atorvastatin 40 mg in high cardiovascular risk patients with primary hypercholesterolemia: a randomized, double-blind, active-controlled, multicenter study. Lipids Health Dis. 2012 Jan 31;11:18 | CrossRef | PubMed |
  21. Piorkowski M, Fischer S, Stellbaum C, Jaster M, Martus P, Morguet AJ, et al. Treatment with ezetimibe plus low-dose atorvastatin compared with higher-dose atorvastatin alone: is sufficient cholesterol-lowering enough to inhibit platelets? J Am Coll Cardiol. 2007 Mar 13;49(10):1035-42 | PubMed |
  22. Nakamura T, Hirano M, Kitta Y, Fujioka D, Saito Y, Kawabata K, et al. A comparison of the efficacy of combined ezetimibe and statin therapy with doubling of statin dose in patients with remnant lipoproteinemia on previous statin therapy. J Cardiol. 2012 Jul;60(1):12-7 | CrossRef | PubMed |
  23. 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 Dec 18;40(12):2125-34 | PubMed |
  24. Melani L, Mills R, Hassman D, Lipetz R, Lipka L, LeBeaut A, et al. Efficacy and safety of ezetimibe coadministered with pravastatin in patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. Eur Heart J. 2003 Apr;24(8):717-28 | PubMed |
  25. Meaney A, Ceballos G, Asbun J, Solache G, Mendoza E, Vela A, et al. The VYtorin on Carotid intima-media thickness and overall arterial rigidity (VYCTOR) study. J Clin Pharmacol. 2009 Jul;49(7):838-47 | CrossRef | PubMed |
  26. Blagden MD, Chipperfield R. Efficacy and safety of ezetimibe co-administered with atorvastatin in untreated patients with primary hypercholesterolaemia and coronary heart disease. Curr Med Res Opin. 2007 Apr;23(4):767-75 | PubMed |
  27. Masuda J, Tanigawa T, Yamada T, Nishimura Y, Sasou T, Nakata T, et al. Effect of combination therapy of ezetimibe and rosuvastatin on regression of coronary atherosclerosis in patients with coronary artery disease. Int Heart J. 2015 May 13;56(3):278-85 | CrossRef | PubMed |
  28. Masana L, Mata P, Gagné C, Sirah W, Cho M, Johnson-Levonas AO, et al. Long-term safety and, tolerability profiles and lipid-modifying efficacy of ezetimibe coadministered with ongoing simvastatin treatment: a multicenter, randomized, double-blind, placebo-controlled, 48-week extension study. Clin Ther. 2005 Feb;27(2):174-84 | CrossRef |
  29. Blazing MA, Giugliano RP, Cannon CP, Musliner TA, Tershakovec AM, White JA, et al. Evaluating cardiovascular event reduction with ezetimibe as an adjunct to simvastatin in 18,144 patients after acute coronary syndromes: final baseline characteristics of the IMPROVE-IT study population. Am Heart J. 2014 Aug;168(2):205-12.e1 | CrossRef | PubMed |
  30. 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 Jan;7(1):88-97 | PubMed |
  31. 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 Mar;47(3):385-95 | PubMed |
  32. 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 Dec 1;102(11):1495-501 | CrossRef | PubMed |
  33. 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 Aug;20(8):1185-95 | PubMed |
  34. 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 Jun;20(6):955-65 | PubMed |
  35. 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 Sep;54(3):309-19 | PubMed |
  36. Kerzner B, Corbelli J, Sharp S, Lipka LJ, Melani L, LeBeaut A, et al. Efficacy and safety of ezetimibe coadministered with lovastatin in primary hypercholesterolemia. Am J Cardiol. 2003 Feb 15;91(4):418-24 | PubMed |
  37. 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 Aug;60(8):914-21 | PubMed |
  38. 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):1564-72 | CrossRef | PubMed |
  39. 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 Apr;62(4):539-54 | CrossRef | PubMed |
  40. 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 Jun;192(2):432-7 | PubMed |
  41. McKenney JM, Farnier M, Lo KW, Bays HE, Perevozkaya I, Carlson G, et al. Safety and efficacy of long-term co-administration of fenofibrate and ezetimibe in patients with mixed hyperlipidemia. J Am Coll Cardiol. 2006 Apr 18;47(8):1584-7 | PubMed |
  42. 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 Jun;59(6):619-27 | PubMed |
  43. Kastelein JJ, Akdim F, Stroes ES, Zwinderman AH, Bots ML, Stalenhoef AF, et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med. 2008 Apr 3;358(14):1431-43. | PubMed |
  44. Rosen JB, Jimenez JG, Pirags V, Vides H, Hanson ME, Massaad R, et al. A comparison of efficacy and safety of an ezetimibe/simvastatin combination compared with other intensified lipid-lowering treatment strategies in diabetic patients with symptomatic cardiovascular disease. Diab Vasc Dis Res. 2013 May;10(3):277-86 | CrossRef | PubMed |
  45. 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 Mar;24(3):685-94 | CrossRef | PubMed |
  46. Bays HE, Ose L, Fraser N, Tribble DL, Quinto K, Reyes R, 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):1758-73 | PubMed |
  47. Bays HE, Davidson MH, Massaad R, Flaim D, Lowe RS, Tershakovec AM, et al. Safety and efficacy of ezetimibe added on to rosuvastatin 5 or 10 mg versus up-titration of rosuvastatin in patients with hypercholesterolemia (the ACTE Study). Am J Cardiol. 2011 Aug 15;108(4):523-30 | CrossRef | PubMed |
  48. 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 May;180(1):107-12 | PubMed |
  49. 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 May;198(1):198-207 | PubMed |
  50. Kouvelos GN, Arnaoutoglou EM, Matsagkas MI, Kostara C, Gartzonika C, Bairaktari ET, et al. Effects of rosuvastatin with or without ezetimibe on clinical outcomes in patients undergoing elective vascular surgery: results of a pilot study. J Cardiovasc Pharmacol Ther. 2013 Jan;18(1):5-12 | CrossRef | PubMed |
  51. Gagné C, Bays HE, Weiss SR, Mata P, Quinto K, Melino M, et al. Efficacy and safety of ezetimibe added to ongoing statin therapy for treatment of patients with primary hypercholesterolemia. Am J Cardiol. 2002 Nov 15;90(10):1084-91 | PubMed |
  52. 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 May 28;105(21):2469-75 | PubMed |
  53. Feldman T, Koren M, Insull W Jr, 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 Jun 15;93(12):1481-6 | PubMed |
  54. Farnier M, Volpe M, Massaad R, Davies MJ, Allen C. Effect of co-administering ezetimibe with on-going simvastatin treatment on LDL-C goal attainment in hypercholesterolemic patients with coronary heart disease. Int J Cardiol. 2005 Jul 10;102(2):327-32 | PubMed |
  55. Farnier M, Roth E, Gil-Extremera B, Mendez GF, Macdonell G, Hamlin C, 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.e1-8 | PubMed |
  56. Farnier M, Freeman MW, Macdonell G, Perevozskaya I, Davies MJ, Mitchel YB, et al. Efficacy and safety of the coadministration of ezetimibe with fenofibrate in patients with mixed hyperlipidaemia. Eur Heart J. 2005 May;26(9):897-905 | PubMed |
  57. Farnier M, Averna M, Missault L, Vaverkova H, Viigimaa M, Massaad R, et al. Lipid-altering efficacy of ezetimibe/simvastatin 10/20 mg compared with rosuvastatin 10 mg in high-risk hypercholesterolaemic patients inadequately controlled with prior statin monotherapy - The IN-CROSS study. Int J Clin Pract. 2009 Apr;63(4):547-59 | CrossRef | PubMed |
  58. 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 Feb 15;101(4):490-6 | CrossRef | PubMed |
  59. Dobs AS, Guyton JR, McClusky D, Ponsonnet D, Melani L, Lebeaut A (2003). Coadministration of ezetimibe with simvastatin. American College of Cardiology 52nd Annual Scientific Session, Chicago, Illinois (Published in: Journal of the American College of Cardiology. 2003;41(6, Supplement 1):227) | Link |
  60. 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 Dec;30(6):230-5 | PubMed |
  61. Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med. 2015 Jun 18;372(25):2387-97 | CrossRef | PubMed |
  62. Corp., M. S. & D. (2005). IMPROVE-IT: Examining Outcomes in Subjects With Acute Coronary Syndrome: Vytorin (Ezetimibe/Simvastatin) vs Simvastatin (P04103). Clinicaltrials.gov | Link |
  63. 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 Jul;9(4):575-84 | PubMed |
  64. Ballantyne CM, Weiss R, Moccetti T, Vogt A, Eber B, Sosef F, et al. 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 Mar 1;99(5):673-80 | PubMed |
  65. 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 Jun 15;93(12):1487-94. | PubMed |
  66. Ballantyne CM, Lipka LJ, Sager PT, Strony J, Alizadeh J, Suresh R, et al. Long-term safety and tolerability profile of ezetimibe and atorvastatin coadministration therapy in patients with primary hypercholesterolaemia. Int J Clin Pract. 2004 Jul;58(7):653-8 | PubMed |
  67. Ballantyne CM, Houri J, Notarbartolo A, Melani L, Lipka LJ, Suresh R, et al. Effect of ezetimibe coadministered with atorvastatin in 628 patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. Circulation. 2003 May 20;107(19):2409-15 | PubMed |
  68. 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. Am Heart J. 2005 Mar;149(3):464-73. Erratum in: Am Heart J. 2005 May;149(5):882. | PubMed |
  69. 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 May;37(5):357-63 | PubMed |
  70. Dujovne CA, Ettinger MP, McNeer JF, Lipka LJ, LeBeaut AP, Suresh R, et al. Efficacy and safety of a potent new selective cholesterol absorption inhibitor, ezetimibe, in patients with primary hypercholesterolemia. Am J Cardiol. 2002 Nov 15;90(10):1092-7. Erratum in: Am J Cardiol. 2003 Jun 1;91(11):1399 | PubMed |
  71. 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 Apr;21(4):571-8 | PubMed |
  72. 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 Dec;59(12):1377-86 | PubMed |
  73. Baigent C, Landray MJ, Reith C, Emberson J, Wheeler DC, Tomson C, et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet. 2011 Jun 25;377(9784):2181-92 | CrossRef | PubMed |
  74. Arimura T, Miura S, Ike A, Sugihara M, Iwata A, Nishikawa H, et al. Comparison of the efficacy and safety of statin and statin/ezetimibe therapy after coronary stent implantation in patients with stable angina. J Cardiol. 2012 Aug;60(2):111-8 | CrossRef | PubMed |
  75. West AM, Anderson JD, Epstein FH, Meyer CH, Wang H, Hagspiel KD, et al. Low-density lipoprotein lowering does not improve calf muscle perfusion, energetics, or exercise performance in peripheral arterial disease. J Am Coll Cardiol. 2011 Aug 30;58(10):1068-76 | CrossRef | PubMed |
  76. West AM, Anderson JD, Meyer CH, Epstein FH, Wang H, Hagspiel KD, et al. The effect of ezetimibe on peripheral arterial atherosclerosis depends upon statin use at baseline. Atherosclerosis. 2011 Sep;218(1):156-62 | CrossRef | PubMed |
  77. 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 Oct;22(10):2041-53 | PubMed |
  78. 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, placebo-controlled trial. Mayo Clin Proc. 2004 May;79(5):620-9 | PubMed |
  79. Rossebø AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med. 2008 Sep 25;359(13):1343-56 | CrossRef | PubMed |
  80. Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, et al. [2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC)]. G Ital Cardiol (Rome). 2016 Oct;17(10):831-872. | CrossRef | PubMed |
Chan DK, O'Rourke F, Shen Q, Mak JC, Hung WT. Meta-analysis of the cardiovascular benefits of intensive lipid lowering with statins. Acta Neurol Scand. 2011 Sep;124(3):188-95. | CrossRef | PubMed |

Sharma M, Ansari MT, Abou-Setta AM, Soares-Weiser K, Ooi TC, Sears M, et al. Systematic review: comparative effectiveness and harms of combination therapy and monotherapy for dyslipidemia. Ann Intern Med. 2009 Nov 3;151(9):622-30. | CrossRef | PubMed |

Nußbaumer B, Glechner A, Kaminski-Hartenthaler A, Mahlknecht P, Gartlehner G. Ezetimibe-Statin Combination Therapy. Dtsch Arztebl Int. 2016 Jul 1;113(26):445-53 | CrossRef | PubMed |

Pandor A, Ara RM, Tumur I, Wilkinson AJ, Paisley S, Duenas A, et al. Ezetimibe monotherapy for cholesterol lowering in 2,722 people: systematic review and meta-analysis of randomized controlled trials. J Intern Med. 2009 May;265(5):568-80. | CrossRef | PubMed |

Battaggia A, Donzelli A, Font M, Molteni D, Galvano A. Clinical efficacy and safety of Ezetimibe on major cardiovascular endpoints: systematic review and meta-analysis of randomized controlled trials. PLoS One. 2015 Apr 27;10(4):e0124587 | CrossRef | PubMed |

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. 2007 Aug;23(8):2009-26 | PubMed |

Santee J, Lindsey C, Pace H. Relative efficacy of antilipemic agents in non–high-density lipoprotein cholesterol reduction. J Pharm Pract. 2012 Aug;25(4):447-56 | PubMed |

Mikhailidis DP, Lawson RW, McCormick AL, Sibbring GC, Tershakovec AM, Davies GM, et al. Comparative efficacy of the addition of ezetimibe to statin vs statin titration in patients with hypercholesterolaemia: systematic review and meta-analysis. Curr Med Res Opin. 2011 Jun;27(6):1191-210 | CrossRef | PubMed |

Ambegaonkar BM, Tipping D, Polis AB, Tomassini JE, Tershakovec AM. Achieving goal lipid levels with ezetimibe plus statin add-on or switch therapy compared with doubling the statin dose. A pooled analysis. Atherosclerosis. 2014 Dec;237(2):829-37. | CrossRef | PubMed |

Ara R, Tumur I, Pandor A, Duenas A, Williams R, Wilkinson A, et al. Ezetimibe for the treatment of hypercholesterolaemia: a systematic review and economic evaluation. Health Technol Assess. 2008 May;12(21):iii, xi-xiii, 1-212 | PubMed |

Zieve F, Wenger NK, Ben-Yehuda O, Constance C, Bird S, Lee R, et al. Safety and efficacy of ezetimibe added to atorvastatin versus up titration of atorvastatin to 40 mg in Patients > or = 65 years of age (from the ZETia in the ELDerly [ZETELD] study). Am J Cardiol. 2010 Mar 1;105(5):656-63 | CrossRef | PubMed |

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 May;80(5):587-95 | PubMed |

Strony J, Yang B, Hanson ME, Veltri EP. Long-term safety and tolerability of ezetimibe coadministered with simvastatin in hypercholesterolemic patients: a randomized, 12-month double-blind extension study. Curr Med Res Opin. 2008 Nov;24(11):3149-57 | CrossRef | PubMed |

Stein E, Stender S, Mata P, Sager P, Ponsonnet D, Melani L, et al. Achieving lipoprotein goals in patients at high risk with severe hypercholesterolemia: efficacy and safety of ezetimibe co-administered with atorvastatin. Am Heart J. 2004 Sep;148(3):447-55. | PubMed |

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 Dec 1;102(11):1489-94 | CrossRef | PubMed |

Knopp RH, Gitter H, Truitt T, Bays H, Manion CV, Lipka LJ, et al. Effects of ezetimibe, a new cholesterol absorption inhibitor, on plasma lipids in patients with primary hypercholesterolemia. Eur Heart J. 2003 Apr;24(8):729-41 | PubMed |

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 Dec;81(12):1579-88. Erratum in: Mayo Clin Proc. 2007 Mar;82(3):387 | PubMed |

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 May;98(5):772-8 | PubMed |

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 Aug;1(4):264-70 | CrossRef | PubMed |

Hing Ling PK, Civeira F, Dan AG, Hanson ME, Massaad R, De Tilleghem Cle B, et al. Ezetimibe/simvastatin 10/40 mg versus atorvastatin 40 mg in high cardiovascular risk patients with primary hypercholesterolemia: a randomized, double-blind, active-controlled, multicenter study. Lipids Health Dis. 2012 Jan 31;11:18 | CrossRef | PubMed |

Piorkowski M, Fischer S, Stellbaum C, Jaster M, Martus P, Morguet AJ, et al. Treatment with ezetimibe plus low-dose atorvastatin compared with higher-dose atorvastatin alone: is sufficient cholesterol-lowering enough to inhibit platelets? J Am Coll Cardiol. 2007 Mar 13;49(10):1035-42 | PubMed |

Nakamura T, Hirano M, Kitta Y, Fujioka D, Saito Y, Kawabata K, et al. A comparison of the efficacy of combined ezetimibe and statin therapy with doubling of statin dose in patients with remnant lipoproteinemia on previous statin therapy. J Cardiol. 2012 Jul;60(1):12-7 | CrossRef | PubMed |

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 Dec 18;40(12):2125-34 | PubMed |

Melani L, Mills R, Hassman D, Lipetz R, Lipka L, LeBeaut A, et al. Efficacy and safety of ezetimibe coadministered with pravastatin in patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. Eur Heart J. 2003 Apr;24(8):717-28 | PubMed |

Meaney A, Ceballos G, Asbun J, Solache G, Mendoza E, Vela A, et al. The VYtorin on Carotid intima-media thickness and overall arterial rigidity (VYCTOR) study. J Clin Pharmacol. 2009 Jul;49(7):838-47 | CrossRef | PubMed |

Blagden MD, Chipperfield R. Efficacy and safety of ezetimibe co-administered with atorvastatin in untreated patients with primary hypercholesterolaemia and coronary heart disease. Curr Med Res Opin. 2007 Apr;23(4):767-75 | PubMed |

Masuda J, Tanigawa T, Yamada T, Nishimura Y, Sasou T, Nakata T, et al. Effect of combination therapy of ezetimibe and rosuvastatin on regression of coronary atherosclerosis in patients with coronary artery disease. Int Heart J. 2015 May 13;56(3):278-85 | CrossRef | PubMed |

Masana L, Mata P, Gagné C, Sirah W, Cho M, Johnson-Levonas AO, et al. Long-term safety and, tolerability profiles and lipid-modifying efficacy of ezetimibe coadministered with ongoing simvastatin treatment: a multicenter, randomized, double-blind, placebo-controlled, 48-week extension study. Clin Ther. 2005 Feb;27(2):174-84 | CrossRef |

Blazing MA, Giugliano RP, Cannon CP, Musliner TA, Tershakovec AM, White JA, et al. Evaluating cardiovascular event reduction with ezetimibe as an adjunct to simvastatin in 18,144 patients after acute coronary syndromes: final baseline characteristics of the IMPROVE-IT study population. Am Heart J. 2014 Aug;168(2):205-12.e1 | CrossRef | PubMed |

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 Jan;7(1):88-97 | PubMed |

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 Mar;47(3):385-95 | PubMed |

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 Dec 1;102(11):1495-501 | CrossRef | PubMed |

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 Aug;20(8):1185-95 | PubMed |

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 Jun;20(6):955-65 | PubMed |

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 Sep;54(3):309-19 | PubMed |

Kerzner B, Corbelli J, Sharp S, Lipka LJ, Melani L, LeBeaut A, et al. Efficacy and safety of ezetimibe coadministered with lovastatin in primary hypercholesterolemia. Am J Cardiol. 2003 Feb 15;91(4):418-24 | PubMed |

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 Aug;60(8):914-21 | PubMed |

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):1564-72 | CrossRef | PubMed |

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 Apr;62(4):539-54 | CrossRef | PubMed |

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 Jun;192(2):432-7 | PubMed |

McKenney JM, Farnier M, Lo KW, Bays HE, Perevozkaya I, Carlson G, et al. Safety and efficacy of long-term co-administration of fenofibrate and ezetimibe in patients with mixed hyperlipidemia. J Am Coll Cardiol. 2006 Apr 18;47(8):1584-7 | PubMed |

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 Jun;59(6):619-27 | PubMed |

Kastelein JJ, Akdim F, Stroes ES, Zwinderman AH, Bots ML, Stalenhoef AF, et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med. 2008 Apr 3;358(14):1431-43. | PubMed |

Rosen JB, Jimenez JG, Pirags V, Vides H, Hanson ME, Massaad R, et al. A comparison of efficacy and safety of an ezetimibe/simvastatin combination compared with other intensified lipid-lowering treatment strategies in diabetic patients with symptomatic cardiovascular disease. Diab Vasc Dis Res. 2013 May;10(3):277-86 | CrossRef | PubMed |

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 Mar;24(3):685-94 | CrossRef | PubMed |

Bays HE, Ose L, Fraser N, Tribble DL, Quinto K, Reyes R, 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):1758-73 | PubMed |

Bays HE, Davidson MH, Massaad R, Flaim D, Lowe RS, Tershakovec AM, et al. Safety and efficacy of ezetimibe added on to rosuvastatin 5 or 10 mg versus up-titration of rosuvastatin in patients with hypercholesterolemia (the ACTE Study). Am J Cardiol. 2011 Aug 15;108(4):523-30 | CrossRef | PubMed |

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 May;180(1):107-12 | PubMed |

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 May;198(1):198-207 | PubMed |

Kouvelos GN, Arnaoutoglou EM, Matsagkas MI, Kostara C, Gartzonika C, Bairaktari ET, et al. Effects of rosuvastatin with or without ezetimibe on clinical outcomes in patients undergoing elective vascular surgery: results of a pilot study. J Cardiovasc Pharmacol Ther. 2013 Jan;18(1):5-12 | CrossRef | PubMed |

Gagné C, Bays HE, Weiss SR, Mata P, Quinto K, Melino M, et al. Efficacy and safety of ezetimibe added to ongoing statin therapy for treatment of patients with primary hypercholesterolemia. Am J Cardiol. 2002 Nov 15;90(10):1084-91 | PubMed |

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 May 28;105(21):2469-75 | PubMed |

Feldman T, Koren M, Insull W Jr, 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 Jun 15;93(12):1481-6 | PubMed |

Farnier M, Volpe M, Massaad R, Davies MJ, Allen C. Effect of co-administering ezetimibe with on-going simvastatin treatment on LDL-C goal attainment in hypercholesterolemic patients with coronary heart disease. Int J Cardiol. 2005 Jul 10;102(2):327-32 | PubMed |

Farnier M, Roth E, Gil-Extremera B, Mendez GF, Macdonell G, Hamlin C, 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.e1-8 | PubMed |

Farnier M, Freeman MW, Macdonell G, Perevozskaya I, Davies MJ, Mitchel YB, et al. Efficacy and safety of the coadministration of ezetimibe with fenofibrate in patients with mixed hyperlipidaemia. Eur Heart J. 2005 May;26(9):897-905 | PubMed |

Farnier M, Averna M, Missault L, Vaverkova H, Viigimaa M, Massaad R, et al. Lipid-altering efficacy of ezetimibe/simvastatin 10/20 mg compared with rosuvastatin 10 mg in high-risk hypercholesterolaemic patients inadequately controlled with prior statin monotherapy - The IN-CROSS study. Int J Clin Pract. 2009 Apr;63(4):547-59 | CrossRef | PubMed |

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 Feb 15;101(4):490-6 | CrossRef | PubMed |

Dobs AS, Guyton JR, McClusky D, Ponsonnet D, Melani L, Lebeaut A (2003). Coadministration of ezetimibe with simvastatin. American College of Cardiology 52nd Annual Scientific Session, Chicago, Illinois (Published in: Journal of the American College of Cardiology. 2003;41(6, Supplement 1):227) | Link |

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 Dec;30(6):230-5 | PubMed |

Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med. 2015 Jun 18;372(25):2387-97 | CrossRef | PubMed |

Corp., M. S. & D. (2005). IMPROVE-IT: Examining Outcomes in Subjects With Acute Coronary Syndrome: Vytorin (Ezetimibe/Simvastatin) vs Simvastatin (P04103). Clinicaltrials.gov | Link |

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 Jul;9(4):575-84 | PubMed |

Ballantyne CM, Weiss R, Moccetti T, Vogt A, Eber B, Sosef F, et al. 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 Mar 1;99(5):673-80 | PubMed |

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 Jun 15;93(12):1487-94. | PubMed |

Ballantyne CM, Lipka LJ, Sager PT, Strony J, Alizadeh J, Suresh R, et al. Long-term safety and tolerability profile of ezetimibe and atorvastatin coadministration therapy in patients with primary hypercholesterolaemia. Int J Clin Pract. 2004 Jul;58(7):653-8 | PubMed |

Ballantyne CM, Houri J, Notarbartolo A, Melani L, Lipka LJ, Suresh R, et al. Effect of ezetimibe coadministered with atorvastatin in 628 patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. Circulation. 2003 May 20;107(19):2409-15 | PubMed |

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. Am Heart J. 2005 Mar;149(3):464-73. Erratum in: Am Heart J. 2005 May;149(5):882. | PubMed |

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 May;37(5):357-63 | PubMed |

Dujovne CA, Ettinger MP, McNeer JF, Lipka LJ, LeBeaut AP, Suresh R, et al. Efficacy and safety of a potent new selective cholesterol absorption inhibitor, ezetimibe, in patients with primary hypercholesterolemia. Am J Cardiol. 2002 Nov 15;90(10):1092-7. Erratum in: Am J Cardiol. 2003 Jun 1;91(11):1399 | PubMed |

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 Apr;21(4):571-8 | PubMed |

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 Dec;59(12):1377-86 | PubMed |

Baigent C, Landray MJ, Reith C, Emberson J, Wheeler DC, Tomson C, et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet. 2011 Jun 25;377(9784):2181-92 | CrossRef | PubMed |

Arimura T, Miura S, Ike A, Sugihara M, Iwata A, Nishikawa H, et al. Comparison of the efficacy and safety of statin and statin/ezetimibe therapy after coronary stent implantation in patients with stable angina. J Cardiol. 2012 Aug;60(2):111-8 | CrossRef | PubMed |

West AM, Anderson JD, Epstein FH, Meyer CH, Wang H, Hagspiel KD, et al. Low-density lipoprotein lowering does not improve calf muscle perfusion, energetics, or exercise performance in peripheral arterial disease. J Am Coll Cardiol. 2011 Aug 30;58(10):1068-76 | CrossRef | PubMed |

West AM, Anderson JD, Meyer CH, Epstein FH, Wang H, Hagspiel KD, et al. The effect of ezetimibe on peripheral arterial atherosclerosis depends upon statin use at baseline. Atherosclerosis. 2011 Sep;218(1):156-62 | CrossRef | PubMed |

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 Oct;22(10):2041-53 | PubMed |

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, placebo-controlled trial. Mayo Clin Proc. 2004 May;79(5):620-9 | PubMed |

Rossebø AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med. 2008 Sep 25;359(13):1343-56 | CrossRef | PubMed |

Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, et al. [2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC)]. G Ital Cardiol (Rome). 2016 Oct;17(10):831-872. | CrossRef | PubMed |

Edición Julio 2022
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