Is ezetimibe/simvastatin no better than simvastatin alone? Lessons learned and clinical implications

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An example is Senator John McCain, who, according to his recently released medical records, has a Framingham 10-year risk of more than 20% and was on ezetimibe/simvastatin to treat an elevated cholesterol level. After release of the ENHANCE trial, he was switched to generic simvastatin, and his LDL-C increased from 82 mg/dL to 122 mg/dL. He most likely has an LDL-C goal of less than 100 mg/dL according to the ATP III guidelines, and he is therefore no longer at his target.

For physicians in the community, questions from concerned patients

For the physicians who have received hundreds of phone calls and e-mails from concerned patients, the ENHANCE trial results must have been both discouraging and confusing. At present, I think we should remember the following:

  • Ezetimibe’s mechanism of action is well understood
  • It is safe and well-tolerated
  • It still has a role as an add-on to statin therapy (or as monotherapy or combined with other agents in those who cannot tolerate statins) for patients who have not yet achieved their LDL-C target.

For the pharmaceutical industry, enormous challenges

The neutral ENHANCE trial results created an uncomfortable situation for the trial sponsor. A heavily marketed drug failed to achieve its expected result after the study results were delayed for a few months. The pharmaceutical industry ranks 14th out of 17 industries in public trust among the American public, and this study provided an opportunity for its critics to attack what is, in their opinion, an overly marketed drug.

Enormous challenges are on the horizon for the pharmaceutical industry, with a shrinking pipeline of potential new drugs, increasing regulatory hurdles, greater liability risk, political pressure for price controls, enhanced scrutiny of sales practices, and a growing media bias. As a cardiologist and clinical researcher whose father died at age 47 of a myocardial infarction, I am concerned that, unless change occurs, a vibrant pharmaceutical industry with the financial and intellectual capital to find and develop new, more effective treatments will cease to exist.

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