The announcement earlier this week by the US Food and Drug Administration (FDA) that the high-dose formulation (80 mg per day) of the cholesterol-lowering drug simvastatin (Zocor) should not be prescribed for new patients was long awaited by critics of the drug, who questioned why the agency did not take such action sooner. Studies suggest that use of simvastatin may elevate a patient’s risk of developing myopathy, or muscle injury, resulting in muscle pain, tenderness, or weakness. In rare cases, the most serious form of myopathy can damage the kidneys and lead to kidney failure.
One vocal critic, cardiologist Steven E. Nissen, MD, of the Cleveland Clinic, first questioned the safety of simvastatin in 2004 in an editorial in JAMA. The editorial commented on study findings indicating that high-dose simvastatin, while increasing the risk of myopathy, was no better than low-dose simvastatin in reducing major cardiovascular events such as heart attack or stroke in patients with acute coronary syndrome. Results of another study (called REACH) of patients who had previously experienced a heart attack, announced in 2008, showed similar findings and eventually prompted the FDA to issue a safety announcement in March 2010 about the increased risk of myopathy in patients taking high-dose simvastatin.
“The agency is extraordinarily slow to act on safety issues and has compromised patients—I don’t understand its reluctance,” said Nissen. “The evidence against simvastatin was probably there in 2004, and that evidence was strengthened by the REACH results in 2008.” Given that there were 2 statins available that were better at lowering low-density lipoprotein cholesterol, the “bad” cholesterol, “it’s surprising how long it took to remove the drug ,” he added.
Critics say there are potential conflicts built into how drugs are regulated in the United States that may not serve patients well. For example, user fees from the pharmaceutical industry now constitute more than half of the FDA’s funding of its approval process for new drugs. Another potential problem is that the FDA is responsible for both granting approval for a new drug and for restricting or banning its use when safety issues come to light.
“Removing a drug means admitting you made a mistake in the first place, and that’s hard for people to do,” said Nissen. “Many people, including me, have called for a separation of these responsibilities so that the group responsible for postmarketing decisions involving a drug would be different from the group that approves the drug in the first place.”