Rosuvastatin (Crestor, AstraZeneca) had a higher risk rate for muscle-related side effects than five other leading statins in an analysis of seven years of FDA adverse case reports. Higher potency agents were associated with elevated relative risk of adverse events, according to researchers, who recommended that physicians consider potency when prescribing statins to manage cholesterol.
The results were published online Aug. 22 in PLOS One.
Randomized clinical trials for statins provided critical data for FDA approval of the drugs but their patient selection did not reflect the broad spectrum of the real-world population, wrote Beatrice Golomb, MD, PhD, professor in the departments of medicine and family and preventive medicine at the University of California, San Diego, and colleagues. Consequent side effects such as rhabdomyolysis and muscle and tendon disorders emerged after approval, including a warning from the FDA in 2011 on the increased risk of myopathy with the 80 mg dose of simvastatin.
“When a drug safety problem is important enough to merit regulatory action, earlier detection is presumably better, enabling more adverse events to be forestalled,” they wrote. “Careful post-approval monitoring for adverse events is therefore vital to the continuing drug evaluation process.”
Golomb and colleagues used data mining techniques to analyze case reports filed between July 1, 2005 and March 31, 2011, in the FDA Adverse Event Reporting System. They focused the search on atorvastatin (Lipitor, Pfizer), simvastatin (Zocor, Merck), lovastatin (Mevacor, Merck), pravastatin (Pravachol, Bristol-Myers Squibb), rosuvastatin, fluvastatin (Lescol, Novartis) and generic equivalents. They looked for “primary suspect” and “all suspect” adverse events, which they then used to derive a “ranked risk” calculation.
The relative risk rates for rosuvastatin were consistently higher than other commonly used statins. Atorvastatin and simvastatin had intermediate risks and pravastatin and lovastatin showed the lowest risk rates. With the exception of fluvastatin, relative risk appeared to track with potency.
“Higher potency agents, and rosuvastatin in particular, were associated with elevated relative risk of adverse events,” they wrote. “This finding has important implications for statin treatment decisions in general, and particularly with regard to patients who have already experienced muscle-related adverse events from statin therapy.”
They continued that while randomized controlled clinical trials are the gold standard in research, they may have limited ability to detect adverse events in the real-world clinical scenario. Post-market surveillance such as their analysis also has limitations, including inaccurate data and under-reporting, but may provide a method for identifying important adverse events.
"These findings underscore that stronger statins bear higher risk and should be used with greater caution and circumspection," Golomb said in a release.
The authors suggested that the data offer reference points for selecting statins, particularly for cholesterol management of patients who experienced muscle-related side effects. “We believe that our results warrant the attention of healthcare providers, drug developers, patients and regulatory professionals involved with statins and other cholesterol-related medications,” they concluded.