JAMA: Docs question how expanded statin indications should affect practice
Since the FDA expanded indications for rosuvastatin (Crestor, AstraZeneca) in February, physicians have questioned its place in clinical practice, based on a perspective published in the April 7 issue of the Journal of the American Medical Association.
In early February, the FDA approved rosuvastatin for use to prevent cardiovascular disease (CVD) in men over the age of 50 and women aged 60 or higher and for those who met other criteria such as having a high-sensitivity C-reactive protein (hsCRP), or at least one additional CV risk factor.
However, some physicians believe that the agency’s approval needs more evidence as it is based on only one clinical trial, the JUPITER trial.
In the perspective, JAMA writer Mike Mitka wrote that basing evidence off one singular trial is “an action that goes against the accepted norms of having a group of leading researchers reviewing all of the evidence and then making recommendations.”
JUPITER trial results showed those patients with lipoprotein cholesterol levels of 130 mg/dL or less and hsCRP levels of 2.0 mg/L or higher, treated with a 20 mg/d of rosuvastatin exhibited almost a 44 percent reduction of risks. The trial compared those administered rosuvastatin to those with placebo.
“The FDA ought to be very clear that these are not guidelines and represent a response to one clinical trial,” said Scott M. Grundy, MD, PhD, of the University of Texas Southwestern Medical Center in Dallas.
“Are you going to let the FDA write the cholesterol guidelines in a backdoor manner instead of the National Cholesterol Education Program?" said Grundy.
"If I end up with a JUPITER patient, I would do the standard risk panel," said James H. Stein, MD, professor of medicine at the University of Wisconsin School of Medicine in Madison, Wis. "If I determined they were at intermediate risk [based on the Framingham risk assessment] but they did not qualify for lipid therapy, I would do a CRP test and act on that if it was elevated,” said Stein.
High hsCRP readings said Stein, have a correlation with obesity and excess weight. Instead, Stein said, “We should work on the lifestyle factor that directly affects CRP, and that is adiposity.”
Stein explained that the available, approved statin therapy could cause a "medication creep," which he says occurs as physicians administer daily pills rather than start a change in a patients lifestyle as a preventative measure.
Stein and Steven E. Nissen, MD, chairman of the Cleveland Clinic Foundation’s department of cardiovascular medicine, also raised that rosuvastatin could be too expensive for patients without insurance, costing patients almost $140 per month.
Nissen and Stein pinpointed the effectiveness of the statin as a “class effect” and suggested that a substitution for rosuvastatin for patients without insurance or who cannot afford the drug would have the same effect.
However, on the other side of the argument, Thomas A. Pearson, MD, PhD, of the University of Rochester Medical Center in Rochester, N.Y., urged that physicians exhibit caution when finding and administering alternatives to the drug.
"I would be a defender of heterogeneity in our pharmacopeia for drugs within a class, and there is error on the part of third-party payors in saying all statins are the same," he said.
The FDA's Endocrinologic and Metabolic Drugs Advisory Committee gave the first nod of approval of the expanded indication in December 2009.
In early February, the FDA approved rosuvastatin for use to prevent cardiovascular disease (CVD) in men over the age of 50 and women aged 60 or higher and for those who met other criteria such as having a high-sensitivity C-reactive protein (hsCRP), or at least one additional CV risk factor.
However, some physicians believe that the agency’s approval needs more evidence as it is based on only one clinical trial, the JUPITER trial.
In the perspective, JAMA writer Mike Mitka wrote that basing evidence off one singular trial is “an action that goes against the accepted norms of having a group of leading researchers reviewing all of the evidence and then making recommendations.”
JUPITER trial results showed those patients with lipoprotein cholesterol levels of 130 mg/dL or less and hsCRP levels of 2.0 mg/L or higher, treated with a 20 mg/d of rosuvastatin exhibited almost a 44 percent reduction of risks. The trial compared those administered rosuvastatin to those with placebo.
“The FDA ought to be very clear that these are not guidelines and represent a response to one clinical trial,” said Scott M. Grundy, MD, PhD, of the University of Texas Southwestern Medical Center in Dallas.
“Are you going to let the FDA write the cholesterol guidelines in a backdoor manner instead of the National Cholesterol Education Program?" said Grundy.
"If I end up with a JUPITER patient, I would do the standard risk panel," said James H. Stein, MD, professor of medicine at the University of Wisconsin School of Medicine in Madison, Wis. "If I determined they were at intermediate risk [based on the Framingham risk assessment] but they did not qualify for lipid therapy, I would do a CRP test and act on that if it was elevated,” said Stein.
High hsCRP readings said Stein, have a correlation with obesity and excess weight. Instead, Stein said, “We should work on the lifestyle factor that directly affects CRP, and that is adiposity.”
Stein explained that the available, approved statin therapy could cause a "medication creep," which he says occurs as physicians administer daily pills rather than start a change in a patients lifestyle as a preventative measure.
Stein and Steven E. Nissen, MD, chairman of the Cleveland Clinic Foundation’s department of cardiovascular medicine, also raised that rosuvastatin could be too expensive for patients without insurance, costing patients almost $140 per month.
Nissen and Stein pinpointed the effectiveness of the statin as a “class effect” and suggested that a substitution for rosuvastatin for patients without insurance or who cannot afford the drug would have the same effect.
However, on the other side of the argument, Thomas A. Pearson, MD, PhD, of the University of Rochester Medical Center in Rochester, N.Y., urged that physicians exhibit caution when finding and administering alternatives to the drug.
"I would be a defender of heterogeneity in our pharmacopeia for drugs within a class, and there is error on the part of third-party payors in saying all statins are the same," he said.
The FDA's Endocrinologic and Metabolic Drugs Advisory Committee gave the first nod of approval of the expanded indication in December 2009.