More information on NSAIDs & CV risk

- Jennifer Middleton, MD, MPH

Have your patients been asking about non-steroidal anti-inflammatory drug (NSAID) safety? I've seen several lay press articles recently regarding a couple of new NSAID safety studies, and they are definitely prompting patients to ask questions in my office. Both studies reinforce the cardiovascular risks we already know about NSAIDs.

The first study scrutinized four European countries' population health registries for an association between current oral NSAID use and risk of admission to a hospital for acute heart failure. The authors matched individuals in these databases who were admitted with heart failure and had been using an NSAID in the last 14 days ("current" use) to individuals of a similar age, gender, and health risk who were not admitted and had used NSAIDs previously ("past" use, defined by use at least 183 days prior). Those individuals with "current" use of any NSAID were more likely to be admitted with heart failure compared to those with "past" use (odds ratio 1.19 [95% confidence interval 1.17-1.22]). Regarding particular NSAIDs, ibuprofen, naproxen, indomethacin, and diclofenac all increased the risk of heart failure admission while celecoxib, etodolac, and meloxicam did not.

The second study, conducted in Denmark, examined the association between out of hospital cardiac arrest and oral NSAID use in the 30 days prior. All cases of cardiac arrest in Denmark are entered into a registry, and the researchers excluded individuals with obvious non-cardiac causes of arrest (trauma, overdose, etc). Every prescription in Denmark is tracked via another registry, and most NSAIDs used there are prescribed; over the counter NSAID availability in Denmark is quite limited (only small quantities of low dose ibuprofen may be purchased without a prescription). The researchers found the use of any NSAID to increase the risk of out of hospital cardiac arrest (OR 1.31, 95% confidence interval 1.17-1.46), which was mostly driven by ibuprofen and diclofenac's effect - by far the most commonly prescribed NSAIDs there.

NSAID safety concerns are nothing new; this 2009 AFP article advises us to be cautious before prescribing NSAIDs to patients at increased risk of bleeding along with chronic heart, liver, and/or kidney problems. I've written previously on the blog about a large meta-analysis published in 2013 showing that long term NSAID use increased the risk of heart failure. These two new studies, however, may cast even short term safety of NSAIDs in a questionable light. Neither set of researchers commented on how long patients had been taking NSAIDs who were "current" users, but it seems possible that at least some of the individuals in these cohorts were not using them long-term.

These studies provide us with more information to discuss with patients when considering options for acute or chronic pain relief. Although oral NSAID use increased cardiovascular risks in both of these studies, the odds ratios in each study were not terribly high; this increase in risk might be more acceptable to many patients - and physicians - than the risks of opioids. With the ever-growing awareness of opioid misuse, we'll have to decide with each patient which set of risks and benefits are the most acceptable. Topical NSAIDs may also be worth including in conversations about treating acute musculoskeletal pain.

Will these new studies change how you discuss NSAIDs with patients?