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Ezetimibe prescribing soars in the United States as compared with Canada


Use of a controversial new cholesterol lowering drug, ezetimibe (trade names Zetia, Ezetrol, Vytorin), has increased in the United States, far beyond that seen in Canada, where direct-to-consumer advertising (DTCA) is prohibited, and there is more government regulation of drug reimbursement in publically funded drug formularies. Worldwide sales for ezetimibe were estimated at $5 billion in 2007.

A new study from California’s Western University of Health Sciences in partnership with Ontario’s Institute for Clinical Evaluative Sciences (ICES) and Yale University in Connecticut, found that over a recent four-year period, yearly prescriptions for ezetimibe prescriptions in the U.S. grew to over 33 million, while in Canada with 1/10 of the American population, ezetimibe only grew to 824,000 prescriptions. In 2006, ezetimibe accounted for 15% of all cholesterol lowering prescriptions in the United States, while in Canada, it only represented 3.4%. “Our study finds substantial differences in how cholesterol lowering medications are used in the two countries. These results are especially noteworthy given the recent release of the ENHANCE study results involving Vytorin in January 2008,” says lead author Dr. Cynthia Jackevicius, “The ENHANCE study found no decrease in the progression of atherosclerosis despite Vytorin lowering bad LDL cholesterol levels as expected, reinforcing uncertainty about the clinical benefits of ezetimibe.”

Scientists followed health data over a five year period (2002-2006) to describe the adoption of ezetimibe relative to other lipid lowering agents (LLA) and compared the use between Canada and the United States. Canada represents a relevant comparison group because there are population similarities, but critical market differences in drug promotion and product availability. Although ezetimibe has been shown to significantly lower LDL (“bad”) cholesterol levels, there is no published scientific evidence yet, that it reduces the risk of heart attacks or death unlike the more extensively studied statin medications. The Canadian government has restricted its coverage of this medication in publically funded formularies to patients who cannot tolerate statins or those who cannot lower their cholesterol levels to target levels with statins alone. However, the drug is much more widely available as a first-line treatment in the U.S. Co-author and ICES senior scientist Dr. Jack Tu says, “Canada’s conservative approach to the adoption and reimbursement of new drugs has been criticized by many in both the U.S and Canada, but such policies in this case not only may have saved money, but also prevented wider use of a new medication with uncertain outcome benefits.”

The results:

  • Over four years LLA prescriptions rose from 3,719 to 7,401 /month per 100,000 population in Canada and from 3,927 to 6,827 per month per 100,000 population in U.S.
  • The proportion of all LLA prescriptions accounted for by ezetimibe rose from 0.2% in 2003 to 3.4% in 2006 in Canada, while in the U.S it rose from 0.1% in 2002 to 15.2% in 2006.
  • Statin use was relatively constant between 2002 and 2006 in Canada, while the proportion of statin prescriptions decreased from 86.5% to 80.8% in the U.S.
  • In 2006, the ratio of statin: ezetimibe prescriptions were 26:1 in Canada and 5:1 in the U.S. Ezetimibe(Zetia) expenditures per 100,000 population were more than four-fold higher in the U.S as compared to Canadain 2006.
  • Distinct patterns of use of ezetimibe emerged between the U.S. and Canada from 2002-06, altering the approach to treatment of high cholesterol in the U.S.
  • The U.S.pattern increased overall costs, but the effect on clinical outcomes is uncertain.

Despite the absence of any medical evidence from clinical trials showing that ezetimibe reduces the risk of heart attacks or deaths, Vytorin has been heavily promoted for its supposed superiority over statins alone. According to Nielsen Monitor–Plus, more than $200 million was spent on direct-to-consumer advertising for Vytorin in the U.S during 2007. “Higher ezetimibe use translates into costs that are four times higher in the U.S than in Canada, and we don’t know if this made a difference in preventing heart attacks and saving lives. Being cautious about new medications and monitoring their use using post-marketing surveillance is a good idea, until more evidence is available about potential benefit,” says Dr. Jackevicius.

The study “Use of Ezetimibe in the United States and Canada" is being released online in The New England Journal of Medicine on March 30.

Author affiliations: ICES (Drs. Jackevicius, Tu, Ko); University Health Network (Dr. Jackevicius); Sunnybrook Health Sciences (Drs. Tu, Ko); University of Toronto (Drs. Jackevicius, Tu) – Ontario, Canada; Mt. Sinai School of Medicine (Dr. Ross); Western University of Health Sciences (Dr. Jackevicius); Yale University of Medicine (Dr. Krumholz); Yale New Haven Hospital (Dr. Krumholz); Department of Epidemiology and Public Health, Section of Health Policy and Administration (Dr. Krumholz); Robert Wood Johnson Clinical Scholars Program (Dr. Krumholz); United States.

ICES is an independent, non-profit organization that uses population-based health information to produce knowledge on a broad range of healthcare issues. Our unbiased evidence provides measures of health system performance, a clearer understanding of the shifting healthcare needs of Ontarians, and a stimulus for discussion of practical solutions to optimize scarce resources. ICES knowledge is highly regarded in Canadaand abroad, and is widely used by government, hospitals, planners, and practitioners to make decisions about care delivery and to develop policy.


  • Kristine Galka
  • Institute for Clinical Evaluative Sciences (ICES)
  • Direct: 416.629.8493 or 416.480.4780


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