Newly published analysis of the adverse event reports filed during the first year rosuvastatin was on the U.S. market showed that its use was linked to significantly more adverse events than other statins.
From October 2003 to September 2004, more than 5 million prescriptions for rosuvastatin (Crestor) were filled in the United States. Rosuvastatin use was associated with about 28 adverse events reports of rhabdomyolysis, proteinuria, nephropathy, or renal failure for every 1 million prescriptions filled, a rate two to eight times higher than that for atorvastatin (Lipitor), pravastatin (Pravachol), or simvastatin (Zocor), according to a report published online (Circulation [Epub ahead of print], May 23, 2005. Article DOI number: 10.1161/circulationaha.105.555482. Available at www.circ.ahajournals.org
But experts differed on the clinical message of these findings.
“This additional safety information is important for both patients and physicians to consider, among other factors, when balancing the risks and benefits in choosing a statin,” said Richard H. Karas, M.D., director of the Preventive Cardiology Center and the Women's Heart Center at Tufts-New England Medical Center in Boston, and senior author of the new report. He and his associates concluded that “it would seem prudent at the current time for health care providers to consider other statins as first-line therapy.”
A more skeptical reading of the findings was given by Scott M. Grundy, M.D., who wrote an editorial that accompanied the report (Circulation [Epub ahead of print], May 23, 2005. Article DOI number: 10.1161/circulationaha.105.557652. Available at www.circ.ahajournals.org
“I don't see any clear-cut evidence to choose one statin over another,” he said during a press briefing. “On the basis of this study, I don't know that rosuvastatin is more dangerous” than other statins, said Dr. Grundy, director of the Center for Human Nutrition at the University of Texas Southwestern Medical Center in Dallas.
Dr. Grundy cited the limitations of adverse event reports as a way to gauge the safety of a drug and to compare safety among drugs. He also noted that in March 2005, the Food and Drug Administration denied a request to remove rosuvastatin from the U.S. market that had been filed last year by Sidney M. Wolfe, M.D., director of the Health Research Group of Public Citizen.
“The FDA had the same database [that Dr. Karas used] and they did not determine that rosuvastatin was more dangerous [than other statins],” Dr. Grundy said at the press briefing. “The disagreement is about whether the evidence is strong enough evidence to say that there is a difference [among statins]. The new paper says there might be, but the FDA did not reach that conclusion.”
The new study analyzed reports for a variety of individual adverse events, such as myopathy and liver effects, as well as for several combinations of events including the primary analysis, which totaled the reports of rhabdomyolysis, proteinuria, nephropathy, or renal failure.
The analysis looked at reports for all statins during the first 12 months when rosuvastatin was available in the United States, as well as reports that were made during the year when each statin was first available. This additional analysis was included because adverse event reports are often more common when a drug is first sold, Dr. Karas said.
The consistent pattern in virtually all of these comparisons was that the number of adverse event reports for rosuvastatin was significantly higher than for atorvastatin, pravastatin, or simvastatin.
Dr. Karas noted that the adverse events associated with rosuvastatin did not seem to be linked with overdosing, because the average dosage in these reports was 17 mg/day, and more than 60% of patients in the reports received 10 mg/day or less. The approved dosage for rosuvastatin is 5–40 mg/day.
Despite the significantly higher relative risk linked to rosuvastatin use, Dr. Karas as well as the other speakers at the press briefing stressed that the absolute incidence of adverse events was low with rosuvastatin as well as with all other approved statins.
“This paper heightens our sensitivity to the possibility of a signal of increased adverse events with rosuvastatin, but it has limitations,” commented Elliott Antman, M.D., director of the coronary care unit at Brigham and Women's Hospital in Boston and senior associate editor of Circulation.
“The overarching issue is to get patients [who need treatment] on statins to help achieve their lipid goals. If rosuvastatin is the statin that is most available to a patient based on insurance reimbursement, then that's perfectly acceptable,” Dr. Antman said.