OTC NSAIDs and cardiovascular safety

OTCs Today

Almost 27 million Americans have osteoarthritis, including one-third of adults older than 65 years.1 An additional 1.5 million individuals have rheumatoid arthritis (RA).1 The risk of developing cardiovascular disease (CVD) in patients with rheumatologic conditions is significantly increased over that of the general population, especially for individuals with RA and similar inflammatory rheumatologic diseases. The primary explanation for this finding has focused on the inflammatory process being linked to both RA and CVD, but concerns about the potential contribution of NSAIDs have also been identified.

According to the American College of Rheumatology (ACR), acetaminophen should be a first-line treatment for managing pain in patients with osteoarthritis.2 Compared with NSAIDs, acetaminophen has a better safety profile, although some patients report better pain relief using NSAIDs.2

The ACR recommends low-dose NSAIDs when analgesia from acetaminophen is insufficient.2 Although ibuprofen and naproxen both block COX-1 and COX-2, the drugs may differ in their cardiovascular effects. Because of naproxen’s longer half-life of 14 hours, its use may result in prolonged platelet inhibition in some patients.3 However, the relative cardiovascular safety of OTC NSAIDs has remained controversial, as well as the safety of OTC ibuprofen versus naproxen in patients taking warfarin.

NSAIDs: Risks vs. benefits

A 2013 meta-analysis analyzed the use of NSAIDs and coxibs in patients with osteoarthritis or rheumatoid arthritis for their risk of cardiovascular and upper gastrointestinal adverse effects.4 At a dosage of 2400 mg/d, ibuprofen significantly increased major coronary events defined as nonfatal myocardial infarction (MI) or coronary death but did not increase the risk of major vascular events. In contrast, naproxen 1000 mg daily did not significantly increase either coronary or vascular events. Neither NSAID increased the risk of stroke; however, both were associated with a doubling of the risk of hospitalization due to heart failure. Most patients in these trials were not at high risk for vascular disease; thus actual findings may be different in patients with underlying cardiovascular disease. 

FDA has concluded that insufficient evidence exists to claim that naproxen is safe in patients with cardiovascular disease. An ongoing randomized, double-blind study is assessing the comparative benefits and risks of ibuprofen, naproxen, and celecoxib in patients with or at risk of CVD.5

Advising patients

In addition to general cardiovascular safety of NSAIDs, many patients with osteoarthritis and RA may have conditions such as atrial fibrillation and will be taking warfarin or oral antithrombotic agents.3 For these individuals, acetaminophen should be tried first; if pain relief is not achieved, NSAIDs may be considered. 

Based on the 2013 meta-analysis, naproxen seems safer compared with ibuprofen; however, patients on concomitant warfarin therapy should be counseled about the increased bleeding risk and need for close monitoring regardless of the NSAID being used. If the pain is severe, patients should talk to their primary care clinician or rheumatologist, as other treatments are available. 

OTC NSAIDs offer relief to thousands of people daily, yet there are risks to consider in certain individuals. Pharmacists should take advantage of opportunities to speak with as many at-risk people as possible to ensure the safe use of NSAIDs and to minimize potential complications in patients with CVD. 


  1. www.cdc.gov/arthritis/data_statistics/arthritis_related_stats.htm
  2. Arthritis Care Res 2012;64;465–72. 
  3. In: Brunton LL, Chabner BA, Knollmann BC (Eds), Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 12th ed. New York: McGraw-Hill; 2011. 
  4. Lancet 2013;382;769–79. 
  5. http://clinicaltrials.gov/show/NCT00346216