The US Food and Drug Administration (FDA) will soon ask drugmakers to update the labels for all non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) after reviewing mounting evidence linking the drugs to increased risk for heart attack and stroke.
In total, drugs containing any of 18 listed active ingredients will be affected by the labeling change, including common over-the-counter (OTC) products such as Advil, Motrin and Aleve, as well as prescription drugs such as Celebrex and Daypro.
NSAIDs are one of the most widely used classes of drugs worldwide and are used to treat common conditions such as pain, fever and headaches.
For years, regulators have known about increased risk for heart attack and stroke from NSAIDS, especially when taken in high doses for prolonged periods.
Then in 2004 and 2005, two high-profile drugs, Merck's Vioxx and Pfizer's Bextra, respectively, were pulled from the market due to increased risk for heart attack and stroke.
In 2004, after studies linked Vioxx to heart attacks and other serious cardiovascular events, Merck withdrew the drug from the market before FDA could take action. The following year, FDA asked Pfizer to voluntarily recall Bextra, after a study showed patients taking the drug suffered more than twice as many heart attacks and strokes as patients in the control group.
This prompted FDA to ask manufacturers to add a boxed warning to all prescription NSAIDs, "highlight[ing] the potential for increased risk of cardiovascular events." FDA also asked the makers of OTC non-aspirin NSAIDs to add "more specific information" about the potential for cardiovascular risks and stronger language about adhering to dosage and duration instructions.
In the intervening years, FDA has continued to review the safety profile of NSAIDs, and in 2014, the agency's Arthritis Advisory Committee and Drug Safety and Risk Management Advisory Committee met to review a decade's worth of studies to determine the safety profile for NSAIDs.
The review concluded that all non-aspirin NSAIDs carry an increased risk for heart attack and stroke. Alarmingly, the committee found some studies showed "significant cardiovascular risk within days to weeks" of starting on certain NSAIDs, and found that even healthy patients had slightly increased risk, though the risk was not nearly as high as it was for patients with existing heart conditions or other risk factors.
As a result, FDA is recommending drugmakers update the labels for all non-aspirin NSAIDs to include the following information:
- "The risk of heart attack or stroke can occur as early as the first weeks of using an NSAID. The risk may increase with longer use of the NSAID."
- "The risk appears greater at higher doses."
- "It was previously thought that all NSAIDs may have a similar risk. Newer information makes it less clear that the risk for heart attack or stroke is similar for all NSAIDs; however, this newer information is not sufficient for us to determine that the risk of any particular NSAID is definitely higher or lower than that of any other particular NSAID."
- "NSAIDs can increase the risk of heart attack or stroke in patients with or without heart disease or risk factors for heart disease. A large number of studies support this finding, with varying estimates of how much the risk is increased, depending on the drugs and the doses studied."
- "In general, patients with heart disease or risk factors for it have a greater likelihood of heart attack or stroke following NSAID use than patients without these risk factors because they have a higher risk at baseline."
- "Patients treated with NSAIDs following a first heart attack were more likely to die in the first year after the heart attack compared to patients who were not treated with NSAIDs after their first heart attack."
- "There is an increased risk of heart failure with NSAID use."
FDA Safety Announcement