What You Need to Know About Zetia and Vytorin

If cholesterol has been a problem for you, your healthcare provider may have suggested the cholesterol-lowering drugs Zetia (ezetimibe) or Vytorin (ezetimibe plus simvastatin) as potential treatment. There has been some controversy over the years about the effectiveness and side effects of ezetimbe. More recent research and American Heart Association guidelines have helped clarify the drug's most effective usage.

The Vytorin cholesterol drug.
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Origins of Zetia and Vytorin

For decades, statins have been the front-line drug therapy for lowering cholesterol. Zocor (simvastatin) is one of the most prescribed and is classified as a moderate-intensity statin at 20 to 40 milligrams (mg) per dose; the therapy should lower a patient's LDL ("bad") cholesterol by 30% to 49%. It's also classified as low-intensity at 10 mg (lowering LDL by less than 30%).

Ezetimbe is not a statin. While statins prevent the liver from producing too much cholesterol, ezetimbe is a selective cholesterol absorption inhibitor, which means it works to prevent the intestines from absorbing cholesterol, forcing the liver to use existing cholesterol in the blood to do its job.

Ezetimbe was approved by the U.S. Food and Drug Administration (FDA) in 2002 as an alternative to statins and marketed under the brand name Zetia. Vytorin was developed as a combination of Zetia and Zocor, which was intended to enhance Zocor's cholesterol-fighting properties.

Vytorin was introduced to the public in 2004 through TV ads that claimed Vytorin could fight the two sources of cholesterol: food and genes. Heavy marketing of Zetia, and then later Vytorin, quickly catapulted U.S. cholesterol prescriptions of these drugs.

Research on Effectiveness

In January 2008, Merck/Schering Plough Pharmaceuticals—the maker of both Zetia and Vytorin—released the results of a study on the effects of the combination of ezetimibe and simvastatin versus simvastatin alone.

This study compared 720 patients taking either Vytorin or Zocor. By using ultrasounds to examine the neck arteries of these patients from both groups, researchers hoped to determine if the combination drug, Vytorin, had lowered the incidence of plaque buildup in their arteries better than the statin alone.

The study indicated that Vytorin patients had no less plaque in their arteries than those taking only Zocor. In fact, those taking Vytorin actually had slightly more plaque.

A second study, called the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT), measured outcomes in more than 18,000 patients who had previously had a heart attack.

The results, reported in 2015, found significantly more patients on the Vytorin (ezetimibe/simvastatin) regimen met their targets for both LDL cholesterol and C-reactive protein (CRP, a cardiac inflammatory marker) than those on simvastatin alone. They had better health outcomes if they met both targets, as measured by cardiovascular death, major coronary event, or stroke.

Also, their risk of a repeat heart attack or stroke was reduced by 6%. The combined therapy showed no significant adverse effects, especially related to the risk of cancer.

One reason for the improved results: The first study covered only 720 people and the newer study looked at 18,000 over a longer period. Time and a larger research cohort showed Vytorin to be beneficial despite the controversy.

When Is Zetia or Vytorin Prescribed?

According to American Heart Association guidelines for cholesterol treatment, ezetimibe is considered a second-line therapy. Statins remain the "cornerstone" therapy, although ezetimibe is the most-prescribed non-statin cholesterol drug.

Currently, healthcare providers may prescribe Zetia or Vytorin for people who need to have low LDL cholesterol levels and cannot reach those levels with high-dose statin therapy or who cannot tolerate high-dose statin therapy.

For instance, the target LDL cholesterol level for a person who has been treated with acute coronary syndrome (heart attack or unstable angina) is less than 50 mg/dL. If the LDL cholesterol level is higher than 50 mg/dL despite a high-dose statin, many cardiologists may then add Zetia or Vytorin.

Side Effects

Ezetimibe and statins are generally well-tolerated. Some potential side effects to watch for include:

  • Headache
  • Nausea
  • Diarrhea
  • Muscle or joint pain (myopathy)
  • Allergic reaction, including rashes or swelling
  • Symptoms of liver or gallbladder inflammation, including severe abdominal pain and unusually colored urine and stools

Side effects may lessen or resolve as your body adjusts to the medication.

What to Do If You're Not Sure About Your Prescriptions

If you have been prescribed Zetia or Vytorin and you're not sure it's right for you, check with your healthcare provider. Ask whether there are circumstances that should keep you on the current course of treatment or if you should begin to explore some alternatives.

If your healthcare provider advises that you stay the course with Vytorin or Zetia:

  • Continue following the recommended lifestyle changes related to diet, exercise, and smoking avoidance to keep your cholesterol in check.
  • Keep your appointments and note any changes in your lipid panel to determine whether your drug therapy is working as expected.
  • Monitor your day-to-day symptoms and report any side effects you may be experiencing to your healthcare provider.

A Word From Verywell

The FDA continues to evaluate the findings of studies to determine whether any action is warranted. If you believe that you have suffered from side effects, or if you have experienced an adverse event such as a heart attack or stroke while taking Vytorin or Zetia, you are asked to report it to the FDA's MedWatch Adverse Event Reporting program.

5 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. American Heart Association. Cholesterol medications.

  2. Food and Drug Administration. Vytorin.

  3. Kastelein JJ, Akdim F, Stroes ES, et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med. 2008;358(14):1431-43. doi:10.1056/NEJMoa0800742

  4. Lancellotti P, Pierard LA, Scheen AJ. Acute coronary syndrome and lipid-lowering therapy. Does the IMPROVE-IT study make any difference?. [Article in French] Rev Med Liege. 2015 Sep;70(9):450-5.

  5. Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med. 2015;372(25):2387-97. doi:10.1056/NEJMoa1410489

Additional Reading

By Lia Tremblay
Lisa Tremblay is an award-winning writer and editor, writing for magazines, websites, brochures, annual reports, and more for over 15 years.