Tuesday, August 16, 2011

All In For Crestor

The American Heart Association will be holding its annual meeting this November.  Cardiobrief.org just posted the announced "late-breaking" clinical trials. These are the big name trials that usually grab a lot of headlines. One of the trials is the AIM-HIGH trial which showed that Niacian didn't really do much in patients whose bad cholesterol or LDL was controlled with a statin (see my post What to do about Niacin? )
Another very important study will also be presented that same November 15th, 2011: Comparison of the Progression of Coronary Atherosclerosis for Two High Efficacy Statin Regimens with Different HDL Effects: SATURN Study Results.  The SATURN study is the Astra Zeneca (makers of Crestor) study comparing high dose Crestor (40mg) with high dose Lipitor (80mg).

Patients in the SATURN study will have known cardiac disease as indicated by a need for coronary angiography (angiogram) and angiographic evidence of coronary disease.  The main end point is  is IVUS-assessed change in the percent atheroma volume in a >40-mm segment of a single coronary artery; which is a "doctor" way of saying they are going to look for plaque build up in the artery.  This is the same end point used in the famous (or infamous) ENHANCE trial which showed that adding Zetia to simvastatin (zetia + simvastatin = Vytorin) did absolutely nothing to plaque build up ( Vytorin and Zetia: What to do now? )

What's interesting about SATURN is that the LDL lowering properties of the highest doses of Crestor and Lipitor are about the same.  However, at those doses Crestor raises the HDL or good cholesterol by about 8% where Lipitor only raises HDL by 3%.  Other studies have shown that plaque build up in the arteries (atherosclerosis) that causes heart attacks and strokes, is not just about LDL, but also about HDL.  Other studies looking at high doses of Crestor when compared to placebo show that it can prevent plaque build up and possibly even lead to regression.  The Lipitor data on this is less robust.

The timing of the results at the AHA is particularly interesting, since it will coincide with Lipitor going generic.  Zocor or simvastatin has been generic for a while, and works well in many patients.  However, patients requiring more aggressive reduction in their cholesterol will not meet their goals on simvastatin and high dose simvastatin is associated with side effects, which prompted a recent FDA warning. (See Don't Take High Dose Simvastatin). Thus, the need for a generic potent statin like Lipitor is huge.  However, this could mean that insurers will make it very, very difficult for patients to get Crestor.  UNLESS......... SATURN proves that high dose Crestor compared to high dose Lipitor significant reduces plaque build up in high risk patients.
Therefore, the SATURN trial is really a huge gamble for Astra Zeneca.  When Merck's ENHANCE trial showed that Vytorin didn't really do more than the generic statin, prescribing rates dropped precipitously. Crestor likely faces the same fate is SATURN turns out to be a negative study.


Michael D. Shaw said...

Dr. Matthew--

I guess that there's no chance that despite the mountains of evidence showing that the cholesterol theory (and its continuing modification) of heart disease is pure bunk, and the sometimes devastating side effects of statins, you would ever change your mind.

You IM guys really have to get off the losing track of....

Someone sets a blood titer, based on usually very questionable research, followed by drugs to "improve" this titer, followed by the drug being taken off the market, followed by no improvement in outcomes, anyway.

Have you people all lost your capacity for original thought?

Dr. Matthew Mintz said...

Please provide the "mountains of evidence" that cholesterol theory is "pure bunk." I would agree that the data for patients at low risk for heart disease is weak, but for patients with high risk for cardiovascular events, particularly diabetics, there is relatively hard outcomes data showing that lowering LDL with a statin prevents heart attacks and stroke. In contrast, there is almost no clinical data (and some suggesting even harm) with use of antioxidants like Vitamin C and E. Since you recommend antoxidants to smokers not ready to quit, I don't think we will likely agree on most things.