High Dose Statin Better

Old studies never die, they just get better.  As published in JACC 54:2009:2290-5 Dr C. Michael Gibson (who is a member of our Scientific Advisory board) is the lead author of an article regarding PCI-PROVE IT a study that we participated in.

This study evaluated what happened to those patients that had an angioplasty and then were given either high dose statin in the form of Lipitor 80mgs day or lower dose statin in the form of pravastatin 40mgs day.

It showed that patients receiving high dose atorvastatin (Lipitor) had a significant reduction in adverse cardiovascular events when compared with a moderate dose statin.  The end points in this study were all cause mortality, myocardial infarction, unstable angina leading to rehospitalization, revascularization after thirty days and stroke.  This reduction is 22% above the benefit of the comparison of statins vs. placebo in other trials.  Most interesting this benefit did not extend to the less than one third of the patients who were treated medically in the trial. 

Why do high dose statins provide a better benefit?  This is not entirely due to the lowering of lipid to an LDL of 70.  That is the goal level in patients that have either angioplasty or coronary bypass surgery.  The effect is referred to as “pleiotropic” and the effects are thought to include a reduction in inflammation (as in Crestor’s new approval for use in “normal” cholesterol levels with high CRP levels), plaque stability and the improvement of endothelial function.

Perhaps the most interesting finding is that this effect takes place within 30 days and then persists throughout the use of the medication.  There is no “fall off’ of the effect and the group of patients who do not take the high dose can not “catch up.”

What this means is that after angioplasty patients should take the highest dose of statin for the maximal benefit.  This has been shown in other studies also.  This concept is difficult to get across to both patients and insurance companies.  The insurance companies are constantly trying to switch my patients to a cheaper statin after I have achieved goal LDL levels.  Further, patients are not used to the concept of more is better with drugs.

It appears that at least in Lipitor’s case the 80mg dose may fit everyone the best

Tags: Angioplasty, lipitor, Myorcardial Infarction, Statins
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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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Reload of Lipitor Before Angioplasty May Have Some Benefits

Statins have been found to have many attributes that are not always readily explainable.  Recently, an article was published in JACC concerning the ARMYDA-RECAPTURE trial.  Done in Italy, this study was designed to investigate whether receiving an acute reload of Lipitor before an angioplasty protects patients, who are chronically on Lipitor after periprocedural heart attacks.

383 patients were studied, who were on chronic statin therapy and needed angioplasty.  These patients were either stable or unstable.  They were randomized 1:1.  Half received 80mg Lipitor 12 hours before and 40 mg Lipitor right before the angioplasty.  The other half got none.  All the patients took 40mg Lipitor after the procedure.

The end points were cardiac death, myocardial infarction, or unplanned repeat angioplasty.  These events occurred in 3.7% of treated patients and 9.4% of untreated patients.  The difference was primarily driven by the finding of more myocardial infarctions in the untreated group.

One further finding was that most of the benefit was in the unstable patient group.  9 unstable patients need to be treated for one patient to have a benefit.  In the stable group,  111 patients need to be treated for one to have a benefit.

Reloading of high dose Lipitor may become a “standard of care” if this study is borne out by other work.  If you are asked to take pills right before an angioplasty it’s because we are trying to provide you with “evidence based medicine,” which is derived from clinical research trials.  These benefits are what we work for on a daily basis.  It is our commitment to our community here at the Jim Moran Heart and Vascular Research Institute.

Tags: Angioplasty, lipitor, Myocardial Infarction, Statins
Posted in Cardiac Surgery, Heart Failure, Myocardial Infarction | No Comments »