Blog | Monday, September 26, 2011

All in for Crestor

The American Heart Association will be holding its annual meeting this November. 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 Niacin 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?)

178/365 All In by thebarrowboy via Flickr and a Creative Commons licenseAnother very important study will also be presented that same Nov. 15: 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 AstraZeneca (makers of Crestor) study comparing high dose Crestor (40 mg) with high dose Lipitor (80 mg).

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 IVUS-assessed change in the percent atheroma volume in a greater than 40-mm segment of a single coronary artery, which is a "doctor" way of saying they are going to look for plaque buildup 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 buildup (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 buildup 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 buildup 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 buildup in high-risk patients.

Therefore, the SATURN trial is really a huge gamble for AstraZeneca. 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 if SATURN turns out to be a negative study.

Matthew Mintz, MD, is a Fellow of the American College of Physicians. He is board certified in internal medicine and has been practicing for more than a decade. He is also an Associate Professor of Medicine at an academic medical center on the East Coast. His time is split between teaching medical students and residents, and caring for patients. This post originally appeared at Dr. Mintz' Blog. Conflict-of-interest disclosures are available here.