People taking cholesterol-lowering drugs may often complain of muscle problems, such as pain and weakness. But, did you know the strength or potency of the drugs may be the cause? According to a study from the University of California, San Diego School of Medicine, this may be the case.
The development of these symptoms has now been linked to the potency of the drugs, better known as statins, and these adverse effects are commonly reported to the U.S. Food and Drug Administration (FDA).
“These findings underscore that stronger statins bear higher risk — and should be used with greater caution and circumspection,” said investigator Beatrice Golomb, MD, PhD, professor in the Departments of Medicine and Family and Preventive Medicine at the University of California, San Diego.
Golomb teamed up with researchers from California-based AdverseEvents, Inc., using the company’s software platform to conduct a detailed examination of statin side-effect data from the FDA’s Adverse Event Reporting System (AERS). The study analyzed muscle-related adverse events linked to each of the major statin drugs in total of 147,789 AERS reports, gathered between July 2005 and March 2011.
Looking at the most commonly used statins, AstraZeneca’s Crestor, known generically as rosuvastatin, was found to cause the most frequent number of muscle problems followed by Lipitor (atorvastatin), Zocor (simvastatin), Pravachol (pravastatin) and Mevacor (lovastatin).
“Incorporating all muscle categories, rates for atorvastatin, simvastatin, pravastatin, and lovastatin were, respectively, 55 percent, 26 percent, 17 percent, and 7.5 percent as high, as rosuvastatin, approximately tracking per milligram potency”, the researchers wrote in their report.
“These rankings closely match the individual potencies of each statin. Thus, the strength of the statin drug appears to be a dominant factor in determining how likely muscle problems are to occur,” said Golomb, who directs the Statin Adverse Effects Study at UC San Diego.
Rates were determined for each statin by tallying reports of muscle side effects, standardized to the number of prescriptions filled for that drug. This was done for individual muscle side effects, as well as for side effects overall.
“The FDA AERS data analyzed in this study, however, suggests that the higher potency of rosuvastatin may more than offset any safety advantages due to such factors,” Golomb said. She added that pooled analysis of statin studies in patients with stable heart disease do not indicate that higher strength statins result in a lower death rate. Therefore, “evidence showing that stronger statins may pose a greater risk of side effects is particularly important.”
“Post-marketed studies utilizing AERS data are becoming increasingly important to understand the lasting side effect risks of widely used medications in disparate populations. Until recently, conducting such studies has been difficult due to the fractured and inaccessible nature of the FDA’s raw data,” said Brian Overstreet, CEO of AdverseEvents. The study utilized the company’s unique data sourcing method called RxFilter™, which analyzed more than 140,000 AERS case reports filed with FDA over a six-year time period.
“Only a fraction of adverse effects are reported to the FDA, and a range of factors can influence reporting rates and accuracy of this information,” Golomb said. “However, findings from this study align with — and extend — other forms of evidence.”
For instance, an earlier study from Golomb’s group at UC San Diego showed that patients with muscle problems related to statins often found relief from symptoms after stopping one statin. However, muscle pain or weakness consistently redeveloped if the patient was then placed on a higher potency statin, while patients placed on a lower potency statin had significantly lower risk of recurrence.
“Our findings suggest that individual statin potency is a critical determinant of how likely a statin is to cause problems,” Golomb concluded. “This information should help guide prescribing decisions for statins by offering more information on the risk-benefit profile of the class. It should also be important for guiding decisions about statin selection and use after a patient has experienced a muscle-related adverse event.”
This study was published online by PLoS ONE.