January 25,2008

Grassley comments on the American College of Cardiology clarifying its position on ezetimibe (Zetia)


TO: Reporters and Editors

FR: Jill Kozeny, 202/224-1308for U.S. Sen. Chuck Grassley of Iowa

RE: Questions about statements regarding drug trial

DA: Friday, January 25, 2009

Sen. Chuck Grassley made the comment below about the American College ofCardiology clarifying its position today on ezetimibe (Zetia). In an email from CEO Jack Lewin,the College stated, “The benefits of statins have been proven in large studies, while the effect ofezetimibe is unproven.” The text of the email appears below Sen. Grassley’s quote. TheCollege’s January 15 statement is below today’s email message, along with a statement madeyesterday by Sen. Grassley about the ENHANCE study.

“I’m glad to see that the ACC is putting doctors and patients first. I can only wonderwhat took them so long. I look forward to their continued cooperation with my investigation,”said Sen. Chuck Grassley of Iowa, Ranking Member of the Committee on Finance.ACC Email on ENHANCE, released on January 25, 2008.

From: Jack Lewin [mailto:jlewin@acc.org]

Sent: Friday, January 25, 2008 10:55 AM

To: Board of Governors

Subject: ACC Response to ENHANCE

Dear BOG:

By now you may have heard through media reports or word-of-mouth that the ACC isreceiving inquiries from Congress and others regarding the release of a January 15 publicstatement regarding the ENHANCE trial. The College's intent in issuing this statement was toadvise our physician members looking for guidance in light of the ENHANCE trial data release.A long delay in the release of the data and highly focused media attention led to questions andconcerns from our members and their patients. Our statement was designed to minimize unduepanic and guide our physicians in communicating with patients about the new data.The following statement further clarifies our position in light of recent inquiries and newsreports:

“The American College of Cardiology (ACC) is concerned that recent news reports andadvertisements for ezetimibe (zetia) and ezetimibe/simvastatin (vytorin) could be misinterpretedby patients as an ACC endorsement of ezetimibe for first-line treatment for high LDL (badcholesterol) or to reduce further risks of coronary heart disease.

The ACC and American Heart Association have published guidelines which recommendthat a statin be given as first-line treatment and that alternatives be used only when statins fail tobe effective or are associated with significant side effects. The benefits of statins have beenproven in large studies, while the effect of ezetimibe is unproven.

Nonetheless, if patients taking medications have questions about their treatment, theyshould discuss concerns with their physician before making any changes.

The ACC has provided guidance to all our members regarding the recent findings.”The ACC will of course cooperate fully with all congressional requests for informationrelated to the January 15 statement, including sharing our commitment to patient-centeredquality and a high standard of professional ethics.

Thank you for your attention to this important matter.



ACC Statement on ENHANCE Trial

January 15, 2008

The ENHANCE (Effect of Combination Ezetimibe and High-Dose Simvastatin vs.Simvastatin Alone on the Atherosclerotic Process in Patients with Heterozygous FamilialHypercholesterolemia) trial results were released by Merck and Schering-PloughPharmaceuticals on January 14, 2008. The results of the trial show no benefit from thecombination of ezetimibe (Zetia) and simvastatin (sold together as Vytorin) over simvastatinalone in terms of affecting the rate of atherosclerosis progression.

The study involved 720 patients with heterozygous familial hypercholesterolemia andshowed no significant difference in the primary endpoint between patients treated with ezetimibeand simvastatin versus patients treated with simvastatin alone over a two-year period. The studywas designed to prove that Vytorin could slow the growth of plaque in carotid arteries supplyingthe brain more than simvastatin alone. Media reports indicate that the results of the trial show nobenefit from the combination of ezetimibe (Zetia) and simvastatin (sold together as Vytorin) oversimvastatin alone.

The American College of Cardiology recommends that major clinical decisions not bemade on the basis of the ENHANCE study alone.

According to the American College of Cardiology (ACC), this study deserves seriousthought and follow-up. The overall incidence rates of cardiac events were nearly identicalbetween both treatment groups, and both medicines were generally well tolerated. There shouldno be reason for patients to panic. The difference in IMT changes between the simvastatin groupand the Vytorin group was 0.006 mm vs. 0.011 mm.

Health care professionals should speak to their concerned patients using this drug. TheACC is also releasing a public statement explaining that this is not an urgent situation andpatients should never stop taking any prescribed medications without first discussing the issuewith their health care professional. Further research will be needed in this area to provideconclusive evidence about which lipid lowering strategy is preferred (statin alone vs. statin plusezetimibe).

Furthermore, the ACC notes that this trial is an imaging study and not a clinical-outcomestudy. Conclusions should not be made until the three large clinical-outcome trials are presentedwithin the next two to three years. The ACC recommends that Zetia remain a reasonable optionfor patients who are currently on a high dose statin but have not reached their goal. The ACCalso notes that Zetia is a reasonable option for patients who cannot tolerate statins or can onlytolerate a low dose statin.

Reports also indicate that the ENHANCE trial has been submitted as an abstract to bepresented at the upcoming American College of Cardiology Scientific Session in March, 2008.The late-breaking clinical trial selections by the meeting co-chairs are scheduled to occur in lateJanuary.



TO: Reporters and Editors

FR: Jill Kozeny, 202/224-1308for U.S. Senator Chuck Grassley

RE: Controversy over delayed release of drug trial on Vytorin

DA: Thursday, January 24, 2008

Senator Chuck Grassley, Ranking Member of the Committee on Finance, is asking drugmakers Schering-Plough and Merck to explain when the companies first unblinded ENHANCEtrial results and to account for sales and payments made for the cholesterol drug Vytorin toMedicaid. Senator Grassley has also written to the Securities and Exchange Commission, theAmerican Heart Association and the American College of Cardiology regarding this matter.Copies of all four letters are posted with this statement at http://finance.senate.gov.

Background information:

Schering-Plough and Merck recently released the results of the ENHANCE trial whichstudied whether Vytorin performed as well as a generic statin to lower cholesterol levels.Vytorin is a combination pill of ezetimibe and a generic statin. The ENHANCE trial resultsfound that Vytorin performed just as well as a much cheaper statin. The professionalassociations issued statements at the time the ENHANCE study was released, so Sen. Grassley isasking for more information about contributions to this statement. For the past three years,Senator Grassley has conducted oversight of various federal agencies and companies to ensurethat peer reviewed science forms the basis for decisions in healthcare and healthcare payments.Senator Grassley’s comment:

“In Iowa City, generic simvastatin costs $54.54 for a month’s supply while Vytorin costs$112.46. It’s fair to assume the public would have benefitted from knowing that a less expensivedrug works just as well. Instead, people in Iowa and elsewhere paid more for nearly two yearswhile industry leaders sat on a scientific study that would have revealed this information.”