Seven non-steroidal anti-inflammatory drugs (NSAIDs) – including ibuprofen – and two COX-2 inhibitors increase the risk of heart failure, a new study reveals. Although the study focused on prescription drugs, the findings raise questions about OTC NSAIDs.
Researchers matched 92,163 hospital admissions for heart failure with 8,246,403 controls among adults in four countries (the Netherlands, Italy, Germany and the UK) who started one of 27 NSAIDs. Using a NSAID (including a COX-2 inhibitor) in the preceding 14 days increased the risk of hospital admission for heart failure by 19 per cent compared with patients who used a member of the class more than 183 days (about six months) in the past.
Current use of seven NSAIDs – ketorolac (83 per cent increase), indometacin (51 per cent), piroxicam (27 per cent), diclofenac (19 per cent), nimesulide (18 per cent), ibuprofen (18 per cent) and naproxen (16 per cent) – and two COX-2 inhibitors (etoricoxib (51 per cent) and rofecoxib (36 per cent)) were associated with a significantly increased risk of heart failure, irrespective of whether patients previously had been diagnosed with heart failure and regardless of sex.
Heart failure risk approximately doubled for very high doses (≥ 2 defined daily dose equivalents) of indometacin (odds ratio [OR] 2.5), etoricoxib (OR 2.3), diclofenac (OR 2.2) and rofecoxib (OR 2.0). Medium doses (0.9-1.2 defined daily dose equivalents) of indometacin and etoricoxib both increased the risk by 70 per cent. Some less frequently prescribed NSAIDs (e.g. sulindac, acemethacin and dexibuprofen) also seemed to increase heart failure risk, although these differences were not statistically significant.
While the study analysed prescription NSAIDs, the findings might also apply to OTC NSAIDs. “Although over-the-counter NSAIDs are probably typically used at lower doses, by younger people, and for shorter durations than prescribed NSAIDs, they are sometimes available at the same doses than those prescribed and may be inappropriately overused,” the authors comment. Further studies are needed, they say, to assess “the safety of over-the-counter NSAIDs under the conditions they are typically used”.
(BMJ 2016; 354:i4857)