I yawn every time I hear a Big Pharma rep tell me what a breakthrough their drug is. It’s like news about vitamins and just as often its too good to be true. New drugs are almost always “me too” drugs: cost a lot, do little more than their predecessors. Approved August 12, 2003, Crestor is the latest of the class of drugs known as statins. These drugs lower cholesterol by decreasing synthesis of cholesterol by the liver. So, let us take a look at Crestor, the latest, supposedly greatest, cholesterol drug.
This trial looked at carotid intima-media thickness (CIMT), a measure of the thickness of carotid artery walls, and the effects of Crestor on CIMT over time. Presumably CIMT correlates with coronary heart disease risk. CIMT varies widely among individuals and increases naturally with aging.
The result from the study reads:
middle-aged adults with Framingham risk scores lower than 10% and evidence of subclinical atherosclerosis, rosuvastatin treatment resulted in statistically significant reductions in the rate of progression of maximum CIMT during a 2-year period compared with placebo. Rosuvastatin did not induce regression overall.
Note that there was no regression overall. And, if you read the study or go here you will see how small the effect was. Dr. Michael Lauer, in an editorial to the JAMA article writes: “Should low-risk individuals undergo routine arterial imaging followed by statin therapy when evidence of asymptomatic disease is discovered? On the basis of current evidence, including the METEOR trial, the answer is clearly no.”
Finally, does CIMT measure anything important anyway? Doubtful according to the Rotterdam study published in the Journal Stroke. To quote their abstract: “Adding IMT to a risk function for coronary heart disease and cerebrovascular disease does not result in a substantial increase in the predictive value when used as a screening tool.” Another study, the APSIS studypublished in the European Heart Journal also found CIMT a weak predictor of events.
This trial was an utter failure. If you are physician you’ve probably never heard of it. Why? Because Big Pharma pretty much controls medical information these days. Unless you have time to read the Journals you’ll miss this kind of negative trial; it won’t be talked about.
In the CORONA trial 5011 patients of at least 60 years of age with ischemic congestive heart failure were randomized to placebo or Crestor. After 32.8 months there was no difference in nonfatal heart attacks, nonfatal strokes, death from cardiovascular causes or death from any cause. No differences between Crestor and placebo even though cholesterol levels and high-sensitivity C-reactive protein levels fell substantially in the Crestor group.
This trial, another failure for Crestor, investigated 2776 hemodialysis patients randomized to Crestor or placebo. After 3.8 years, there were no differences between groups in all cause deaths, cardiovascular deaths, nonfatal heart attacks or nonfatal strokes. Crestor did lower cholesterol levels.
JUPITER is an acronym for Justification for the Use of statins in Primary prevention anIntervention Trial Evaluating Rosuvastatin. This trial was reported as a great success.
The Jupiter trial was stopped early. This has been a trend in recent years. Ending trials early tends to exaggerate outcomes and several articles like this one have addressed this problem.
For a good start, how about a quote straight from the US Food and Drug Administration’s web site, the page titled Questions and Answers For Healthcare Professionals: CRESTOR and the JUPITER Trial. They state:
“There was no statistically significant reduction seen for cardiovascular death or hospitalization for unstable angina in individuals receiving CRESTOR compared to those receiving a placebo.”
That’s right, no statistically significant reduction in cardiovascular death. In fact look at table 3 in the NEJM article and you will see, subtracting nonfatal myocardial infarction fromany myocardial infarction in both the Crestor and placebo groups and you will see there were 3 more fatal heart attacks in the Crestor group.
What other insights are found on the FDAs website? The FDA is very specific on the indication they have granted Crestor. Here it is:
This is the first time CRESTOR has been approved for use in the prevention of heart disease in individuals with “normal” low-density lipoprotein (LDL) cholesterol levels and no clinically evident heart disease . . . Based on the limitations above, CRESTOR should only be used for the primary prevention of cardiovascular disease to reduce the risk of heart attack, stroke, or arterial revascularization procedures in individuals without clinically evident coronary heart disease who meet the following criteria:
* Men > 50 years old or women > 60 years old, and
* hsCRP > 2 mg/L, and
* Presence of at least one additional cardiovascular disease risk factor such as high blood pressure, low HDL-C, smoking, or a family history of premature coronary heart disease.
There you have it. A very specific indication. Note that if a patient’s one additional risk factor were smoking, if you could persuade them to quit smoking you could forgo the Crestor, save vastly more money and no doubt improve their health to a greater degree!
The FDA also reported a safety concern: “An unexpected safety finding in the JUPITER trial was an increase in the number of individuals receiving CRESTOR compared to those receiving a placebo who developed diabetes.”
The FDA also admonishes physicians to interpret the results of the Jupiter trial with caution:
The results from the JUPITER trial do not support the use of CRESTOR in all patients with an elevated hsCRP. For example, there was no evidence that CRESTOR provided benefit in individuals with an elevated hsCRP but no traditional cardiovascular risk factors, which include high blood pressure, low HDL-C, smoking, or a family history of premature coronary heart disease.
The best analysis of the JUPITER trial I have read is by Dr. John Abramson, a family physician, Robert Wood Johnson Fellow and member of the clinical faculty at Harvard Medical School. Here are some key points he makes:
* 170 people had to be treated for 1 year to prevent 1 event at a cost of $270,000 for the Crestor alone (doctors visits and labs add to costs)
*400 people had to be treated for 1 year to prevent 1 death at a cost of $580,000 for the Crestor alone
*41% of the patients had metabolic syndrome and 15% smoked, yet there was no counseling on diet and exercise or smoking cessation
Well I hope this was enlightening. I am not trying to disparage Crestor. In fact I like the drug. I prescribe it in certain situations. It lowers LDL better than any other statin and raises HDL better than any other statin. But it is no miracle drug. Statins in general have been over-hyped and their effectiveness exaggerated.