Public Citizen’s Health Research Group already lists certain nonsteroidal anti-inflammatory drugs (NSAIDs) as Do Not Use, and certain others as Limited Use. Recently published research adds to the already mounting evidence that NSAIDs may endanger heart health. This new data confirms our Do Not Use designation for celecoxib (CELEBREX) and has prompted us to reclassify diclofenac (VOLTAREN) from Limited Use to Do Not Use. Furthermore, while researchers state that low-dose ibuprofen (ADVIL,...
Public Citizen’s Health Research Group already lists certain nonsteroidal anti-inflammatory drugs (NSAIDs) as Do Not Use, and certain others as Limited Use. Recently published research adds to the already mounting evidence that NSAIDs may endanger heart health. This new data confirms our Do Not Use designation for celecoxib (CELEBREX) and has prompted us to reclassify diclofenac (VOLTAREN) from Limited Use to Do Not Use. Furthermore, while researchers state that low-dose ibuprofen (ADVIL, MOTRIN, MOTRIN IB) seems to be fairly safe for both cardiovascular and gastrointestinal complications, higher doses reportedly greatly increase the risk of both outcomes.
Recent NSAID research
Valuable information, for patients and doctors, about the increased cardiovascular risks of drugs such as celecoxib and diclofenac needs to be derived from experimental randomized studies and community studies of more typical, and often lower-dose, use. Both have been conducted over the past few years.
A collective statistical review, commonly referred to as a meta-analysis, published in 2013 measured the comparative cardiovascular and gastrointestinal adverse effects of NSAIDs. The review involved data from 639 studies in which more than 300,000 patients were randomized to receive an NSAID or a placebo (or, in some studies, another NSAID). The researchers found that high doses of all drugs in an NSAID subcategory called coxibs — rofecoxib (VIOXX) or celecoxib — as well as diclofenac and ibuprofen increase the risk of major vascular events (nonfatal heart attack, nonfatal stroke or vascular death). The study also showed that high-dose naproxen (ALEVE, ANAPROX, NAPROSYN) is not associated with these increased risks.
A 2011 paper examined 51 nonrandomized, community-based, controlled observational studies. This data enabled the authors to look at comparative risks for a wider range of doses, including lower doses, than would have been possible in an analysis solely of randomized trials such as the 2013 review. The researchers concluded that naproxen and low-dose ibuprofen are least likely to increase cardiovascular risk. But they also found that cardiovascular risk was also significantly elevated with low doses of both celecoxib (26 percent elevation of risk) and diclofenac (22 percent elevation), and the risk rose in each case with higher doses.
A 2013 review in The Lancet added that all NSAIDs (both coxibs and traditional NSAIDs such as naproxen) increase the risks of congestive heart failure and of peptic ulcer complications and other gastrointestinal bleeding. The reviewer found that in both kinds of studies, risk occurred shortly after drug initiation. Observational studies have also shown that risk does not wane over years of continued use but falls quickly after use ceases.
Public Citizen Actions on NSAIDS
What You Can Do
Low-dose ibuprofen and naproxen are least likely to increase cardiovascular risk.
In addition to considering celecoxib and diclofenac Do Not Use drugs because of increased cardiovascular toxicity, Public Citizen lists four other NSAIDs — piroxicam, ketorolac, indomethacin and meloxicam — as Do Not Use for other reasons. You should never stop taking these or any drug without the advice of your physician. Some drugs can cause severe adverse effects when they are stopped suddenly.
The Lancet review, cited above, makes the following additional points, which we strongly endorse:
No available NSAID improves arthritis or prevents progression of painful conditions.
NSAIDs should generally be avoided for patients at high risk of heart failure or with chronic kidney disease.
Though they carry serious risks, and evidence of their efficacy in treatment of chronic pain is not strong, opioids can be used for some patients.
- Patients should use evidence-based nonpharmacological treatments such as application of heat or cold, exercise, or weight loss.
 Coxib and traditional NSAID Trialists’ (CNT) Collaboration. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013;382(9894):769-779. http://dx.doi.org/10.1016/S0140-6736(13)60900-9. Published online May 30, 2013.
 McGettigan P, Henry D. Cardiovascular risk with non-steroidal anti-inflammatory drugs: systematic review of population-based controlled observational studies. PLoS Med. 2011;8:e1001098.
 FDA statement on the halting of a clinical trial of the Cox-2 inhibitor Celebrex. Dec 17, 2004. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2004/ucm108384.htm.