Breaking News: The Crestor Controversy

April 1, 2010

Devyani Kothari, MD

Patients are already talking about a New York Times front page article highlighting the risks associated with statin use as a preventive measure for cardiovascular events in relatively “healthy” people. The piece examines the newest FDA indications for the use of Crestor along with the controversies surrounding the drug.

Last month, the FDA approved Rosuvastatin Calcium, marketed as Crestor by AstraZeneca for use in a new patient population , based on the JUPITER trial. Crestor now carries the indication for the primary prevention of cardiovascular disease (to reduce the risk of stroke and heart attack) in individuals who have no clinically evident heart disease but are at an increased risk of heart disease due to the combined effect of the following risk factors:

o Age (> 50 years in men; > 60 years in women), and
o An elevated high-sensitivity C-reactive protein level (> 2 mg/L), and
o Presence of at least one additional cardiovascular risk factor (e.g., high blood pressure, low HDL-C, smoking, or a family history of premature heart disease).

Under these new guidelines, an estimated additional 6.5 million people in the United States will be eligible to take statins.
Despite these recommendations, many clinicians are skeptical of this new role of statins as a largely preventive measure. Statins are already known to cause myopathy and increased liver enzymes in some patients. In addition, a meta-analysis of 13 randomized statin trials recently published in The Lancet by Sattar et al. showed that statin therapy was associated with a 9% increased risk of developing Type II Diabetes. The JUPITER trial also noted increased physician-reported diabetes in the rosuvastatin group, although there were no significant elevations of fasting blood glucose and only minimal differences in HgA1C.

Furthermore, the new indication for Crestor is based on the level of C-reactive protein, or CRP, an inflammatory marker that has been linked to an increased risk of adverse cardiovascular events. This marker however has not yet achieved the overall acceptance as a marker of risk that traditional lipid levels have.

Adding fuel to the controversy is the fact that the JUPITER trial was funded by AstraZeneca, the manufacturer of Crestor, and one of the authors of the trial, Dr. Paul M. Ridker, invented the CRP test, and receives “undisclosed royalties” every time a doctor orders the test. Moreover, Crestor has its patent until 2016, while Pfizer will lose patent protection on Lipitor next year, pushing the company to expand indications for its drug.

The debate of the role and safety of statins in primary prevention raises very important issues for practicing clinicians. Should a CRP level be ordered on all older patients? How aggressive should doctors be about prescribing statins to healthy patients? Is the CRP a better predictor of cardiovascular disease than lipid levels? The answers still remain to be decided. What should however remain clear to our patients is the clearly proven role of statins in secondary prevention, in patients with known cardiovascular disease. This message needs to be reinforced especially with our cardiac patients who balk at taking statins because they heard on TV that “they are too dangerous.”

References
1. Everett BM, Glynn RJ, MacFadyen JG, Ridker PM. Rosuvastatin in the prevention of stroke among men and women with elevated levels of C-reactive protein: Justification for the use of statins in prevention: An intervention trial evaluating rosuvastatin (JUPITER). Circulation. 2010;121(1):143-150.
2. Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: A collaborative meta-analysis of randomised statin trials. Lancet. 2010;375(9716):735-742.  http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)61965-6/abstract
3. U.S. Food and Drug Administration: “Rosuvastatin Calcium (marketed as Crestor) Information.” http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm109095.htm
4. Wilson, Duff. “Risks Seen in Cholesterol Drug Use in Healthy People.” 31 March 2010. The New York Times. http://www.nytimes.com/2010/03/31/business/31statins.html?ref=health

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