Large Dominant Force or Big Ball of Gas?
The medical world was abuzz on November 20, 2008 when the New England Journal of Medicine (NEJM) printed a ground-breaking study. The article titled “Rosuvastatin to Prevent Vascular Events in Med and Women with Elevated C-Reactive Protein” was published based on data from the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) study. The study was aimed at trying to find a correlation between the use of HMG-CoA reductase inhibitors (commonly called “statins”) and a decrease in cardiovascular events like heart attacks and strokes among others.
You may recognize various drugs in this class as Lipitor (atorvastatin), Pravachol (pravastatin), Zocor (simvastatin), and, the drug under investigation here, Crestor. The main use of these drugs is to lower cholesterol. They have generally had much success and are, as of now, considered very safe. Anecdotally, many physicians have recognized these drugs’ ability not only to decrease cholesterol, but generally decrease the risk of heart disease, stroke, and the like in addition to their effect on cholesterol. Enter the Jupiter study.
The background of the study has to do with the idea that a marker in the body known as C-Reactive Protein (CRP) has recently become associated with an increase risk of cardiovascular disease, when elevated. Now, this doesn’t mean that if it’s elevated you will have disease, simply that if you do have cardiovascular disease, CRP is more likely to be high. What the study wanted to see is if Crestor could effectively bring down levels of CRP in otherwise healthy individuals and whether this had any influence on cardiovascular disease. The results were astounding.
In the study, participants were randomly assigned to two groups, one that received the drug and one that received a placebo (a pill with no actual medication). The trial was set to go for five years, but was stopped just short of two because the results of the data at that point were so good, they could not justify continuing the study and denying some participants this drug. According to the article in the NEJM, Crestor reduced patients LDL (“bad”) cholesterol by 50% and the CRP levels by 37%, and what was more astounding is that heart attacks, strokes, and death from heart disease were reduced by half in the group taking the drug.
The NY times and other media sources immediately jumped on this story, practically elevating Crestor and “statins” as a whole to the level of wonder drug. All the medical community could talk about for a while was this study. We, as medical students in Internal Medicine, received no fewer than 3 separate lectures just on this study alone. You can imagine what happened to AstraZeneca (the makers of Crestor) stock after the release of this study.
It all seemed great and wonderful, but a few things still needed to be addressed. In the mind of Your Humble Observer, testing this drug on patients who, by most criteria, were healthy besides an elevated CRP was fine, but what about groups at higher risk? Can you draw the same conclusions? Besides all of this, the question remains: So what?
It’s great that the drug worked so well for research purposes, but how does this apply clinically? Do we start screening everyone for CRP? Can you even use CRP as an effective screening tool? Who should start receiving “statins”? Too many questions were left unanswered amidst the excitement.
The very same issue of the NEJM featured an article by Dr. Mark Hlatky of Stanford University trying to bring some perspective to the study by asking some of the very same questions posed above. He also brings to light some shortcomings of the study:
”…the trial did not compare subjects with and those without high-sensitivity C-reactive protein measurements, nor did it compare the use of high sensitivity C-reactive protein with the use of other markers of cardiovascular risk.”
His conclusion I believe is the most important consideration for this study:
“Guidelines for primary prevention will surely be reassessed on the basis of the JUPITER results, but the appropriate size of the orbit of statin therapy depends on the balance between the benefits of treatment and its long-term safety and cost.”
Finally, the biggest strike against the study is that it was funded primarily by AstraZeneca which is a huge bias for the study.
The bottom line is, clearly the statins are great medications, and this study shows that they may have wonderful benefits, but we need to approach the use of the drugs in a systematic and objective manner, carefully applying this new information to clinical practice. It will be interesting to see how this information plays out in the years to come with new studies on this subject.
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