And Away Goes Trouble Down the Drain…

In the middle ages, Alchemists dreamed of transmuting coal into gold.  In much the same ways Cardiologists have dreamed of a substance that would remove plaque that had already formed akin to Drano removing scale and rust from pipes.  The best we have so far is statins like Lipitor and Crestor, which has been shown to diminish plaque burden by Intravascular Ultrasound or as it is known IVUS.  The mechanism by which statins work is believed to be more reorganization of plaque than the removal of material.

In June 2003 a study was published in JAMA 2003, which electrified the field of cardiology.  Here was the promise fulfilled, a substance that would remove plaque.  That substance is ApoA-1 Milano now called ETC-216 as it was purchased by Esperion and renamed.

Over the time period November2001 and March 2003, 123 participated in the study.  All had ACS- acute coronary syndrome and I have blogged about this syndrome frequently.  They were randomized into three groups’ placebo, low-dose and high-dose, and underwent once a week infusions of Apo for five weeks.  IVUS was done before and after, and then analyzed to see the differences in plaque volume and composition.

The mean percent decrease was 1.06% in the treatment group and an increase of .14% in the control group.  The absolute reduction in atheroma volume was 4.2% and this carried a p value of <.001.  The lower the p value the more significant thus this is a very significant result.

In the short span of five weeks, atherosclerotic coronary lesions were shown to reverse.  Further, the dose of ApoA-1 did not matter.  Both the low-dose and high-dose had the same effect and it is believed that the mechanism of action is the stimulation of reverse cholesterol transport.

That’s were it ended.  Since 2003 no further work was done because Esperion was purchased by Pfizer and Pfizer was probably doing that to “bury” it because it was working on its blockbuster oral drug torcetrapib.  That failed and Pfizer said adios to cardiac research.

The Medicines Company has a track record of delivering new drugs to market that have not been adequately studied.  Let’s hope that the work will now be started and finished to show whether this compound is the beginning of a new treatment strategy for atherosclerosis.  I will keep you informed.

Tags: Acute Coronary Syndrome, ApoA-1 Milano, Atherosclerosis, atherosclerotic coronary lesions, Crestor, ETC-216, Intravascular Ultrasound (IVUS), lipitor, plaque
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