We refer to the Straits Times article published on 1st April 2008, titled “Two top cholesterol drugs may have no benefits”. We are concerned that this may lead to patients stopping their medications on their own.

The article referred to Vytorin™ and Zetia™. Vytorin™ comprises “Simvastatin” and “Ezetemibe” combined, while Ezetimibe on its own is marketed as Zetia™ (in USA) or Ezetrol™ (in Singapore). The time-tested role of “statins” (e.g. simvastatin) in lowering LDL cholesterol, thus reducing the risk of heart disease, is indisputable. Therefore, to say that both Vytorin™ and Ezetrol™ “may have no benefits” is misleading.

A media release by the companies (Merck and Schering-Plough) prematurely preceded the official report of the ENHANCE study, published on 3rd of April 2008, in the highly-respected New England Journal of Medicine. These results were not presented until 18 months after the study ended. Both these actions, highly frowned upon by the medical community, should not detract from the findings of the study.

True benefit of treatments in the prevention of heart disease may only be apparent after 5 or 10 years. Hence, measurements such as IMT (thickness of neck artery), CRP (a measure of inflammation) and LDL (Low-Density Lipoprotein) have been used as proxies to predict the risk of a future heart attack. The current body of evidence overwhelmingly supports LDL-lowering as the primary measure of reducing heart attack risk. In the ENHANCE study, the addition of Ezetrol™ did demonstrate significantly greater lowering of LDL and CRP, but not IMT, compared to a statin alone. It is noteworthy that simvastatin was prescribed at its maximum dose.

In a statement about the ENHANCE study, the American College of Cardiology states, “This was an imaging study and not a clinical-outcome [e.g. rate of occurrence of heart attack] study. Conclusions should not be made until the three large clinical-outcome trials are presented within the next two to three years.” Major clinical decisions should not be made based on this study alone.

Our current practice, which remains unchanged, is to prescribe affordable generic statins at maximal tolerable doses before the addition of other cholesterol-lowering medications. Alternative cholesterol-lowering medications are considered based on the individual’s concurrent medical conditions and cholesterol profile. Ezetrol? remains a useful addition when statins alone have failed to do its job. Therefore, we strongly advise that patients on Vytorin? or Ezetrol? discuss options with their doctors before discontinuing the use of either medication.

Doreen Tan
Senior Pharmacist, Lipid Clinic & Cardiology Clinic, Alexandra Hospital
Council member, Pharmaceutical Society of Singapore

Lee Siok Ying
Pharmacist, Lipid Clinic, Alexandra Hospital
Drug Information Pharmacist, Alexandra Hospital

Ong Hean Yee
Consultant Cardiologist, Alexandra Hospital

Conflict of interest: None declared.

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