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Zetia and Atherosclerosis


Zetia (Ezetimibe) is a drug that works in conjunction with a class of drugs called statins-Lipitor, Zocor, and Vytorin etc. Zetia augments the effect of statins to lower bad cholesterol (LDL) and to some extent raise good cholesterol (HDL).  Preliminary results of a recent small international trial were released on January 14th, 2008 causing alarm among many patients.  This is unfortunate as there are no conclusive results regarding clinical benefit or harm from Zetia at this time.  

Here are the facts:

  1. This study – Indirect ultrasound methods looked at the thickness of cholesterol plaques in carotid arteries of the neck using indirect ultrasound methods assuming that they would represent the effect on cholesterol plaques in the heart. This study involved 720 patients with a relatively rare and inherited severe increase in blood bad cholesterol (LDL levels greater than 300) followed for less than 2 years. Results showed that in both groups the carotid plaque progressed at a slow rate.  In the statin alone group the progression was 0.000024 inches and in the combination group of Zetia plus statin therapy the progression was 0.000046 inches.  The difference in progression was 0.000022 inches or less than 1/10 of the thickness of a single human hair!
  2. Forty years of clinical trials  - In over forty years of therapy for cholesterol problems there has never been a similar dissociation of an effect on blood fats -cholesterol, etc.- and clinical outcomes.  Therefore, whatever the intervention - whether diet or exercise or any class of drugs that effect cholesterol levels - if the intervention improved blood fat (cholesterol) levels then the clinical trials showed that there is a beneficial effect on clinical outcomes such as reduced heart attacks, strokes, and death.  In order to show these clinical outcomes, such trials need to involve thousands of patients followed over many years.  In fact, there is an ongoing clinical trial at this time that will finally answer the question for Zetia.  This will involve over 10,000 patients and will not be finished until 2011.
  3. What to do in the meanwhile - Until the finished study is performed, we are left with two choices:
    • Stick with the massive amount of clinical data accumulated over the past forty years that is consistently affirmed the relationship of bad cholesterol with bad outcomes.  This would imply that we should all continue to adhere to the guidelines of attempting to lower bad cholesterol as much as possible and below 70mg/dl in patients at high risk or with established disease.  Statins are the traditional first line of therapy and when necessary to achieve the lowering of LDL to the recommended goals, Zetia has proven to be an effective adjunct to the statins offering an additional 25% reduction in bad cholesterol.
    • Alternatively, there are some that will argue for a response to this preliminary trial looking at carotid disease (not heart coronary arteries) in a small group of patients with extremely high cholesterol levels and extrapolate this preliminary data to the larger population of patients with more typical cholesterol numbers.  Those that follow this approach would recommend discontinuing Zetia until the final trial is completed.  It may be that this is too important an issue to be decided by the width of hair.

Please consult your own physician for advice.  There is no need to panic at this preliminary point after one small trial that in the end did not show any difference in clinical outcome involving heart attacks or strokes.

Complications of Atherosclerosis Diagram

Southcoast Physicians Group An affiliate of Southcoast Physicians Group.