Findings from Crestor [Statin] Study

While the headlines are screaming out for your attention to highlight all the 'benefits' of taking a statin cholesterol medication for reducing the risk of a heart attack, let's step back a moment and take a closer look!

The very convincing headline on MSNBC yesterday - Statin drug shown to reverse heart disease - might lead you to believe taking a statin may be a good preventative step to reduce your risk of heart disease. The actual study remains unpublished as it is scheduled for release in JAMA in the April 5, 2006 edition.

From the March 13, 2006 JAMA press release about the study, we learn that the trial included participants with coronary artery disease, specifically atherosclerosis. The study was designed to determine the effects of high-intensity statin therapy on IVUS-derived measures of coronary atherosclerosis regression. This is the first critical item in the study - patients in the study already had established coronary disease. If you read through the MSNBC article however, this tidbit is missing - nowhere in the article are readers informed the study was conducted on those with established coronary artery disease.

The findings are quite impressive - the therapy, which included high doses of Crestor (rosuvastatin) reduced LDL, increased HDL and also resulted in a slight demonstrated regression of their atherosclerosis. On average, LDL fell from 130mg/dL to 60.8mg/dL; HDL rose from 43.1mg/dL to 49mg/DL; and "[f]or the primary efficacy parameter of change in PAV, the average decrease was -0.98 percent and 63.6 percent of patients showed regression of atherosclerosis. For the second primary efficacy parameter, change in atheroma volume in the 10-mm subsegment with the greatest disease severity, there was a median (midpoint) reduction of 9.1 percent in atheroma volume, and 78.1 percent of patients demonstrated regression of atherosclerosis. The secondary efficacy parameter, change in total atheroma volume, showed a 6.8 percent median reduction."

Did you catch those numbers? I hope you did - the study subjects already had pretty good cholesterol levels. While 130mg/dL is the level at which the American Heart Association recommends one consider drug therapy for those with existing coronary heart disease, the participants in this study did not have an alarming LDL level - they were, on average, just at the level to consider a drug intervention. More important, the participants' HDL level was well within the "normal" range of 40-50mg/dL with an average of 43mg/dL.

This leaves me with a question - I wonder if cholesterol really is the end-all-be-all measure in the process of coronary disease as we're repeatedly told? I've wondered this for quite some time actually - and this study just reinforces my doubts. Had the average patient in this study walked into their doctor's office, alarm bells would not have been sounding all that loudly about their cholesterol levels. Even if their clinician was a bit concerned about their LDL, a level of comfort would have come from the HDL readings. Add to that our knowledge that 50% of people who have heart attacks have a normal level of cholesterol.

Hmm...might be easy to say our target levels are still too high. But, to answer that, we also must consider that our target levels truly are accurate and cholesterol isn't really the issue - something else is and we're still missing what that is.With this study we are still missing critical pieces of data - we have no idea what their total cholesterol was, nor do we have any clue what their triglycerides were. We're left in the dark about other known risk factors - like blood pressure, inflammatory markers, weight and activity levels.

Until the publication of the paper, we'll just have to be patient - this additional information is critical to effectively analyze the total effect on cholesterol - did the therapy result in an improved cholesterol ratio? Did it improve triglycerides? Did it have an effect on blood pressure? Did it reduce inflammation? Did participants actively seek to normalize their weight? Were these folks active?

Without the additional data, we simply cannot make a judgement about whether this therapy provided real improvements and/or if there were confounding variables to consider. Yes, the therapy improved LDL and HDL and led to a small regression - but what does that mean for the long-term? At this point, I'm fairly certain that in the long-term, this therapy is not going to be as effective as the headlines want us to believe - it's notable that the press release stated that "[a]dverse events were infrequent and similar to other statin trials."

So, during the term of this study, adverse events [read: deaths and/or other complications or compromises in health] were similar to other studies. At the end of the day, this means that the therapy had little effect on quality of life or whether one would die without the therapy when compared with those using the therapy. Hey, they did improve some measures of their cholesterol and had a regression - but they didn't live longer or better, did they?

I'm not surprised the numerous articles in the media aren't including this information though - it might make someone think twice about whether the positives of the therapy outweigh the negatives. I'm also not surprised that the media isn't highlighting that this was designed as a "secondary prevention" trial - that is to evaluate if a therapy can cut your risk of having another "adverse event" when you've already had one.

This type of study is very different from those designed to evaluate a therapy for "primary prevention" - that is to answer the question of whether a therapy will be effective to reduce the risk of having the first-time "adverse event."

Basically, if a study is not designed to measure primary prevention, its data should not be extrapolated as evidence of efficacy for a healthy population or even a population with a few risk factors who have not yet experienced an adverse event. But, I can almost guarantee that's what's going to happen with this study - we're going to start to see the recommendations call for more aggressive drug intervention in the near future. Just pay no mind to the fact that "[a]dverse events were infrequent and similar to other statin trials."

At least one of the study co-authors did issue a caution in another press release from JAMA regarding the study - Editorial co-author Navin K. Kapur, M.D., a clinical research fellow at Hopkins, adds that, “Researchers’ next steps have to determine whether these very promising results translate into greater reductions in future heart attacks and strokes.”