September 2nd, 2011
Rosuvastatin Fails to Best Atorvastatin in IVUS Study of Atherosclerosis Progression
Larry Husten, PHD
AstraZeneca announced today that its lipid-lowering agent rosuvastatin (Crestor) was not superior to atorvastatin (Lipitor, Pfizer) in reducing the progression of atherosclerosis, as assessed by IVUS.
The company announced the top-line results of SATURN (Study of Coronary Atheroma by InTravascular Ultrasound: Effect of Rosuvastatin Versus AtorvastatiN), which is scheduled to be presented at the American Heart Association meeting in November. The trial compared rosuvastatin (40 mg) with atorvastatin (80 mg) in 1300 high-risk patients.
AstraZeneca said that there was no significant difference between the two groups in the primary endpoint of the study, which was the change from baseline in percent atheroma volume (PAV), as measured by IVUS, but that the absolute numbers favored rosuvastatin. It also reported that the secondary endpoint, the change from baseline in total atheroma volume (TAV), did achieve a statistically significant difference in favor of rosuvastatin.
Analysts and journalists have noted that SATURN was designed to reach completion around the time when Pfizer would lose its patent on Lipitor and that the company had hoped to use the results to persuade people to pay for rosuvastatin in the face of generic atorvastatin. This task will likely be more difficult in the aftermath of SATURN.
In the Wall Street Journal, Sten Stovall wondered if SATURN represented a self-inflicted wound on the part of AstraZeneca. In Forbes, Matt Herper questioned the company’s efforts to diminish the impact of the news:
The result could be worse. AstraZeneca said in its release that there was a trend toward better performance on Crestor and that using a different way of calculating the amount of plaque in the artery the difference was significant. But clinical trials live and die by their primary endpoints, to prevent findings that are just due to chance. This study failed.
Many reports have mentioned the controversy over the ENHANCE trial several years ago, which was also an IVUS trial that missed its endpoint. But rosuvastatin has substantial evidence of benefit in placebo-controlled trials, and no concerns have been raised about the management of SATURN. By contrast, the drug tested in the ENHANCE trial, ezetimibe (Vytorin), had never been shown to produce clinical benefits, and allegations of company tampering with the analysis of the ENHANCE trial provided fuel for the controversy over the trial.
So what have we learned hear?
What DATA do we have correlating outcomes with IVUS progression? The only one that I know is the Periscope trial where Pioglitazone was compared to Sulfonylurea in type II diabetics. Although Pioglitazone was associated with a significant improvement in plaque progression relative to the Sulfonylurea group, it was associated with a very small and statistically insignificant improvement in events. Is there any other DATA out there?
As we subject patients to a dangerous and possibly useless IVUS trial, we should question the sanity of such an endeavor. I think the IRB should be questioned regarding the appropriateness of such a trial. There are better surrogate endpoints to follow.
Competing interests pertaining specifically to this post, comment, or both:
I do not do IVUS studies. I resent the inappropriate use of unproven invasive technologies that put patients in harms way for no clearly demonstrable value.