Friday, July 10, 2015

FDA Strengthens Warnings Of Cardiovascular Risks With NSAIDs


Credit FDA




Between OTC (over-the-counter) sales and prescriptions, NSAIDs (non-steroidal anti-inflammatory drugs) are likely the most commonly consumed class of medication in the world.  Being non-addictive, relatively cheap, and reasonably effective for mild to moderate pain, you’d be hard pressed to find a medicine cabinet anywhere in the world without a bottle of one kind or another.

While most people assume these drugs are perfectly safe if taken as directed – like with all medicines, there are possible downsides.   No drug is 100% benign, 100% of the time.


Although NSAIDs have long been associated with increased risks of gastrointestinal bleeding, it has only been in the past 10 or 15 years that cardiovascular concerns have emerged. 


In 2004 Vioxx, a COX-2 inhibitor which had been marketed by Merck as being less likely to cause stomach bleeding, was abruptly pulled from the market after a study showed that prolonged use increased one’s chances of having a heart attack or stroke.

Bextra, another COX-2 inhibitor, was also recalled after it was linked to increased cardiovascular accidents and to several rare, but potentially deadly, skin disorders.


In 2005, the FDA required the inclusion of a `black box warning’ for prescription NSAIDs and a couple of  years later stiffened the labeling requirements on OTC NSAIDs as well.   In 2011 we explored a pair of studies that looked at NSAID use and the increased risk of cardiovascular events (see NSAIDs and Prior Heart Attacks).



Fast forward to yesterday, and the FDA announced new, stronger cardiovascular risk warnings are to be added to the labels of OTC and prescription NSAIDs.   Essentially, instead of warning that their use might increase the risks of heart attack or stroke, the new warnings will state that they do.


FDA Drug Safety Communication: FDA strengthens warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) can cause heart attacks or strokes

[ 7-9-2015 ]

Safety Announcement

The U.S. Food and Drug Administration (FDA) is strengthening an existing label warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) increase the chance of a heart attack or stroke. Based on our comprehensive review of new safety information, we are requiring updates to the drug labels of all prescription NSAIDs. As is the case with current prescription NSAID labels, the Drug Facts labels of over-the-counter (OTC) non-aspirin NSAIDs already contain information on heart attack and stroke risk. We will also request updates to the OTC non-aspirin NSAID Drug Facts labels.

Patients taking NSAIDs should seek medical attention immediately if they experience symptoms such as chest pain, shortness of breath or trouble breathing, weakness in one part or side of their body, or slurred speech.

NSAIDs are widely used to treat pain and fever from many different long- and short-term medical conditions such as arthritis, menstrual cramps, headaches, colds, and the flu. NSAIDs are available by prescription and OTC. Examples of NSAIDs include ibuprofen, naproxen, diclofenac, and celecoxib (see Table 1 for a list of NSAIDs).

The risk of heart attack and stroke with NSAIDs, either of which can lead to death, was first described in 2005 in the Boxed Warning and Warnings and Precautions sections of the prescription drug labels. Since then, we have reviewed a variety of new safety information on prescription and OTC NSAIDs, including observational studies,1 a large combined analysis of clinical trials,2 and other scientific publications.1 These studies were also discussed at a joint meeting of the Arthritis Advisory Committee and Drug Safety and Risk Management Advisory Committee held on February 10-11, 2014.

Based on our review and the advisory committees’ recommendations, the prescription NSAID labels will be revised to reflect 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.

We will request similar updates to the existing heart attack and stroke risk information in the Drug Facts labels of OTC non-aspirin NSAIDs.

In addition, the format and language contained throughout the labels of prescription NSAIDs will be updated to reflect the newest information available about the NSAID class.

Patients and health care professionals should remain alert for heart-related side effects the entire time that NSAIDs are being taken. We urge you to report side effects involving NSAIDs to the FDA MedWatch program, using the information in the “Contact FDA” box at the bottom of the page.


While the relative risks of having a heart attack or stroke while taking these drugs may alarmingly double, in terms of absolute risk, the numbers only go up a little.  If you currently  have a 1% chance of having a heart attack without taking these drugs, and you double that risk by taking them, you end up with a  2% chance of a cardiovascular mishap.


The FDA offers the following advice to consumers:


What Consumers Should Do

NSAIDs are effective treatments for pain, inflammation and fever. Consumers can still take them but should be aware of this increased risk of heart attack or stroke, especially at higher doses.

“As always, consumers must carefully read the Drug Facts label for all nonprescription drugs. Consumers should carefully consider whether the drug is right for them, and use the medicine only as directed. Take the lowest effective dose for the shortest amount of time possible,” Mahoney says.

When using prescription NSAIDs, read the consumer-friendly Medication Guide attached to your filled prescription, which provides important safety information.

If you have heart disease or high blood pressure, consult a health care provider before using an NSAID. Balance the benefits of NSAIDs with the possible risks and weigh your options. If you take low-dose aspirin for protection against heart attack and stroke, you should know that some NSAIDs, including ibuprofen and naproxen, can interfere with that protective effect.

Stop taking NSAIDs and seek medical help if you experience symptoms that might signal heart problems or stroke, such as chest pain, trouble breathing, sudden weakness in one part or side of the body, or sudden slurred speech.

Reduce your risk factors for heart disease and stroke. “Smoking, high blood pressure, high cholesterol and diabetes are significant risk factors for these conditions,” Mahoney says. “If you smoke, work on quitting. See your doctor regularly to find out if you have these other strong risk factors, and commit yourself to taking care of them and of your health.”


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