Systems Biology:
Method Automates Capture of Cell Image Data
Medical Education
HMS Hospitals Hone Plans for Deeper Cuts in Resident Hours
Clinical Research:
Earliest Cancer Trials May Offer Lower Risk But Lower Benefit
Ambulatory Care:
Postmarketing Study Answers Questions on Statin Safety
Sodium Channel Modulates Calcium-Based T Cell Activation
Drug Ads Need Plainer Language to Explain Risks
Proceedings of the HMS Faculty Council
HMS Appoints Connors as Board of Fellows Chair
Lynn Eckhert Takes Over as AAMC Chair
Dean's Community Service Awards
Broad and Novartis Announce Joint Program to Decode Genetics of Type 2 Diabetes
Center for Large-scale SNP Analysis Backed at Broad Institute
Judge Baker Appoints New President, Opens New Facility
Richmond Award Honors Antismoking Activists
NIH Roadmap Supports Training in Genetics and Complex Diseases
Lefkopoulou Lecturer Describes Approach to Incomplete Data in Longitudinal Studies
Children's Wins $2.5m in Health Surveillance Grants
Cultural Misunderstandings Can Be Opportunities for Learning
Medical Simulator Goes to the Head of the Class
Postmarketing Study Answers Questions on Statin Safety
Statins and other cholesterol-lowering drugs are among the most widely prescribed drugs in the United States. Recent clinical guidelines have expanded the criteria for treating patients with cholesterol-lowering drugs, and studies have looked at using statins to lower heart disease risk in diabetics, for treating Alzheimer's, and for aiding recovery from strokes. But with such high use comes higher scrutiny: how safe are the drugs?
An examination of data from health plans by Richard Platt and colleagues documents the significant risks of a statin that was commonly used before being pulled from the market. (Photo by Steve Gilbert)
In 2001, one popular statin, cerivastatin (Baycol), was pulled from the market after its use was linked with the severe muscle disorder rhabdomyolysis. The move raised concerns that other statins may carry an unacceptable risk of the condition as well. A study conducted by Richard Platt, HMS professor and chair of the Department of Ambulatory Care and Prevention, and his colleagues offers reassurance that three commonly used statins are much safer than cerivastatin. But the study, published in the Dec. 1 Journal of the American Medical Association, confirms cerivastatin's danger: the drug carries 10 times the risk of rhabdomyolysis compared to other statins, and one in 10 patients developed the condition if they took cerivastatin with a fibrate, a class of drugs that lower triglycerides.
Rhabdomyolysis, among the most serious side effects of statins, is a condition in which muscles in the body begin to break down. As the muscle contents spill into the blood, they eventually choke the kidneys, causing kidney damage or failure. "It was clear that catastrophic problems occurred sometimes," Platt said. The problems were "infrequent, but frequent enough that they could influence the choice of treatment. We needed to look at a very large population to get a reasonable idea of how these drugs performed."
| "Many important complications of prescription drugs only become apparent after drugs are in use for a while." |
The incidence of the disorder was similar across the three most commonly prescribed statins--atorvastatin (Lipitor), pravastatin (Pravachol), and simvastatin (Zocor)--and it was very low: .44 per 10,000 person years or about one case out of 20,000 per year. Compared with those medications, fibrate use was associated with a 5.5-fold increase in risk, and combining a statin and a fibrate increased the risk another twofold. The risk was particularly heightened in older patients who also had diabetes. But with cerivastatin, the risk was 10-fold greater than with the other statins, and when cerivastatin was combined with a fibrate, the risk leaped more than 1,400-fold. The researchers estimate that rhabdomyolysis might occur in one out of every 10 patients treated with this combination per year of treatment.
"What we know from this is that the other statins we studied really do have a much lower risk," Platt said. The study, which was funded by the FDA, underscores the importance of clinical studies that analyze drugs after they are on the market. "Many important complications of prescription drugs only become apparent after drugs are in use for a while."
Graham has recently made headlines as a whistleblower at the FDA, accusing the agency of being unable to protect the public from unsafe drugs coming to market. The JAMA paper appears as one of six papers on cerivastatin, including a review of its problems by researchers who participated in litigation against its manufacturer, Bayer Corporation, and two response papers by the company. An accompanying editorial by JAMA's editors calls for changes to remedy the "failures of the current imperfect system for postmarketing surveillance."
The most serious problem, the editors say, is that drug manufacturers are largely responsible for "reporting data from postmarketing studies of their own products." Funding and data for independent studies is not easily found. According to Platt, "Health plans and their data can be extremely important resources in understanding both risks and benefits" of drugs in use, but he added that few health plans are set up to provide data to researchers that would allow these kinds of systematic evaluations.
--Courtney Humphries