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Ezetimibe and simvastatin.svg
Combination of
Ezetimibevia Niemann-Pick C1-Like 1 protein
SimvastatinStatin HMG-CoA reductase inhibitor
Clinical data
Pronunciation/ɛˈzɛtɪmɪb ˌsɪmvəˈstætɪn/
Trade namesVytorin (US), Inegy (EU)
License data
Routes of
By mouth
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • US: ℞-only
  • In general: ℞ (Prescription only)
CAS Number
PubChem CID
CompTox Dashboard (EPA)
Chemical and physical data
Molar mass828.007 g·mol−1
3D model (JSmol)
  • CCC(C)(C)C(=O)OC1CC(C=C2C1C(C(C=C2)C)CCC3CC(CC(=O)O3)O)C.C1=CC(=CC=C1C2C(C(=O)N2C3=CC=C(C=C3)F)CCC(C4=CC=C(C=C4)F)O)O
  • InChI=1S/C25H38O5.C24H21F2NO3/c1-6-25(4,5)24(28)30-21-12-15(2)11-17-8-7-16(3)20(23(17)21)10-9-19-13-18(26)14-22(27)29-19;25-17-5-1-15(2-6-17)22(29)14-13-21-23(16-3-11-20(28)12-4-16)27(24(21)30)19-9-7-18(26)8-10-19/h7-8,11,15-16,18-21,23,26H,6,9-10,12-14H2,1-5H3;1-12,21-23,28-29H,13-14H2/t15-,16-,18+,19+,20-,21-,23-;21-,22+,23-/m01/s1
 ☒NcheckY (what is this?)  (verify)

Ezetimibe/simvastatin is a drug combination used for the treatment of dyslipidemia. It is a combination of ezetimibe (known as Zetia in the United States) and the statin drug simvastatin (known as Zocor in the US).

Ezetimibe reduces blood cholesterol by acting at the brush border of the small intestine and inhibiting the absorption of cholesterol, leading to a decrease in the delivery of intestinal cholesterol to the liver.

Simvastatin is an HMG-CoA reductase inhibitor or statin. It works by blocking an enzyme that is necessary for the body to make cholesterol. Generic versions were approved in 2017.[1] The combination preparation is marketed by Merck & Co. under the trade names Vytorin in the US and Inegy in the European Union. In 2018, it was the 349th most commonly prescribed medication in the United States, with more than 800 thousand prescriptions.[2]


  • Acute liver disease
  • Pregnancy and breast feeding

Side effects[edit]



The combination of ezetimibe and simvastatin is currently[when?] the only product to treat both sources of cholesterol; absorption in the intestine of both biliary and dietary cholesterol, and production in the liver and peripheral tissues.[3] It is thought that the treatment of high cholesterol from both sources is likely to result in lower cholesterol levels,[3] particularly LDL cholesterol. In a clinical study, it was shown that the combination of ezetimibe and simvastatin was superior to atorvastatin in lowering LDL cholesterol.[4]

Clinical trials[edit]

IMPROVE-IT trial[edit]

Published in 2015, the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) randomized 18,144 patients with ACS to simvastatin 40 mg/d plus ezetimibe 10 mg/d or simvastatin alone. With median follow-up of 6 years, simvastatin+ezetimibe was found to reduce the primary outcome of CV mortality, major CV event, or nonfatal stroke (34.7% vs. 32.7%; P=0.016; NNT 50 per 7 years or NNT 350 per 1 year ). There was no reduction in all-cause or CV mortality with simvastatin+ezetimibe, though there was a reduction in MI and stroke.[5]

ENHANCE trial data[edit]

The two-year ENHANCE Study[6] failed to provide evidence that ezetimibe/simvastatin was better than simvastatin (a generic medication) in terms of achieving a lower change from baseline in carotid intima-media thickness despite lower LDL levels in a population of patients with heterozygous familial hypercholesterolemia (a form of high cholesterol that affects less than 1% of patients). Clinical events such as heart attack and stroke were not measured as primary or secondary endpoints of the study making it impossible to determine Vytorin's effect on these events.[7][medical citation needed]

Subsequent debate and enquiries[edit]

The American College of Cardiology released a statement suggesting that "major clinical decisions not be made on the basis of the ENHANCE study alone", given the small and unique patient population, 720 patients in an Amsterdam hospital with heterozygous familial hypercholesterolemia.[8]

Merck and Schering Plough have reported that they have three trials underway to focus on outcomes, measuring the drug's effect on heart attacks and strokes in patients.[7]

These results were presented in full at the American College of Cardiology meeting on 30 March 2008, two years after the last patient completed the study.[9] The House Committee on Energy and Commerce conducted an inquiry into the delayed disclosure of the study data.[citation needed]

Advertising campaign[edit]

In the United States, Vytorin featured a television advertising campaign showing a series of split-screen images of a person and a food item to make the point that cholesterol comes from two sources and can be absorbed from food or manufactured by the body, and that heredity plays a role in the latter.[10] This point is a departure from the commonly held belief that high cholesterol only comes from the food that you eat.[11] In each commercial, the person's features or clothing and the food plated to emphasize the resemblance between the person and the food. For example, in one advertisement a woman wearing a yellow shirt and a pin is juxtaposed with a similarly colored piece of pie.


  1. ^ Clarke T, Grover D (26 April 2017). "Merck cholesterol drug Vytorin faces competition from Impax, Teva generics". Reuters. Retrieved 2 May 2017.
  2. ^ "Ezetimibe; Simvastatin - Drug Usage Statistics". ClinCalc. Retrieved 7 October 2022.
  3. ^ a b "Physicians Agree That Treating Two Sources Of Cholesterol Likely To Achieve Greater LDL-Cholesterol Reductions". Medical News Today. September 4, 2006.
  4. ^ "VYTORIN Superior to Lipitor at Lowering LDL Cholesterol, New Trial Shows". Medical News Today. October 31, 2004.
  5. ^ Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, et al. (June 2015). "Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes" (PDF). The New England Journal of Medicine. 372 (25): 2387–97. doi:10.1056/NEJMoa1410489. hdl:11573/1150638. PMID 26039521.
  6. ^ "Merck, Schering-Plough Release ENHANCE Trial Data". FDA News. January 15, 2008.
  7. ^ a b Park A (2008-01-15). "Is Vytorin a Failure?". Time. Archived from the original on 19 April 2010. Retrieved 2010-05-02.
  8. ^ "Vytorin Results Disappointing, Experts Say Don't Panic". Medical News Today. 16 January 2008.
  9. ^ Herper M (11 April 2008). "The Vytorin Letters". Forbes.
  10. ^ "Chart: Most-Recalled New Prescription Drug Ads 2006-07 TV Season - TVWeek - News". Archived from the original on 2007-11-02. Retrieved 2007-11-05.
  11. ^ "Most Americans do not know that high cholesterol comes from two sources". Medical News Today. July 15, 2004.

External links[edit]