NSAID’s Can Cause Heart Attacks or Strokes

The US Food and Drug Administration (FDA; Silver Spring, MD, USA) is strengthening an existing label warning that nonsteroidal anti-inflammatory drugs (NSAIDs) increase the chance of a heart attack or stroke.

Based on a meta-analysis of randomized clinical trials of cardiovascular and upper gastrointestinal events with NSAIDs conducted at Oxford University (United Kingdom), a comprehensive review of observational studies, and the recommendations of advisory committees, the FDA is requiring label changes and updates to the drug labels of all prescription NSAIDs, including over-the-counter (OTC) non-aspirin NSAIDs that already contain information on heart attack and stroke risk.

Among the reasons cited is that a large number of studies support the finding that NSAIDs cause an increased risk of serious cardiovascular thrombotic events, with varying estimates of how much the risk is increased. Estimates of increased relative risk range from 10%-50% or more, depending on the drugs and the doses studied. Several observational studies found a significant cardiovascular risk within days to weeks of NSAID initiation; some data also showed a higher risk with longer NSAID treatment.

Some observational studies and the meta-analysis suggested that naproxen may have a lower risk for cardiovascular thrombotic events compared to the other NSAIDs; however, the observational studies and indirect comparisons used in the meta-analysis to assess the risk of the nonselective NSAIDs have limitations that affect their interpretability. The FDA advises that variability in patients’ risk factors, comorbidities, concomitant medications and drug interactions, doses being used, duration of treatment, etc., also need to be taken into consideration to make valid comparisons.

There is also evidence of an increased cardiovascular risk from NSAID use by apparently healthy patients. Data from the Oxford meta-analysis, individual randomized controlled trials, and observational studies showed that the relative increase in cardiovascular thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known cardiovascular disease (CVD) or risk factors for CVD. However, patients with known CVD or risk factors had a higher absolute incidence of excess cardiovascular thrombotic events due to their increased baseline rate.

“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,” concluded the FDA advisory. “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.”

Related Links:
US Food and Drug Administration 
Oxford University