NSAIDs association with heart failure risk quantified
medwireNews: The increased risk of heart failure associated with non-steroidal anti-inflammatory drugs (NSAIDs) varies between drugs and according to dose, study findings show.
Data from five population-based healthcare databases from the Netherlands, Italy, Germany and the UK on more than 10 million individuals taking NSAIDs showed that current use (within the past 2 weeks) of any NSAID increased the risk of hospital admission for heart failure by 19% compared with past use (more than 183 days).
A total of 92,163 patients admitted to hospital for heart failure were matched with 8,246,403 control patients according to gender, age and date of cohort entry. The cases had more comorbidities than controls, mainly cardiovascular disease (including acute myocardial infarction, other ischaemic heart diseases, and atrial fibrillation and flutter), and more often received concomitant drug treatment.
A significantly increased risk of heart failure admission was evident for seven traditional NSAIDs – diclofenac, ibuprofen, indomethacin, ketorolac, naproxen, nimesulide and piroxicam – and the two cyclooxygenase (COX)-2 inhibitors etoricoxib and rofecoxib.
But the degree of risk varied according to drug type, with naproxen associated with the smallest increase in risk, at 16%, and ketorolac the highest increase, at 83%.
The researchers also note in The BMJ that the risk of heart failure admission doubled with the current use of very high doses (at or above 2 defined daily dose equivalents) of diclofenac, etoricoxib, indomethacin, piroxicam and rofecoxib compared with past use, while the risk with very high dose naproxen was slightly lower. Even at medium doses (0.9–1.2 defined daily dose equivalents), indomethacin and etoricoxib were associated with a significantly increased risk.
By contrast, celecoxib, the most widely prescribed COX-2 inhibitor, did not increase the risk of hospital admission for heart failure at commonly used doses. The risk associated with higher doses was inconclusive due to the small number of patients involved.
Corrao Giovanni (University of Milano-Bicocca, Milan, Italy) and co-researchers comment that the association between use of each of the individual NSAIDs and heart failure risk was similar for patients with or without prior heart failure and, with a few exceptions, for men and women.
They conclude: “Estimates of the risk of heart failure associated with the use of many individual NSAIDs in this study could help to inform both clinicians and health regulators.”
In a related editorial, Gunnar Gislason (Copenhagen University Hospital, Denmark) and Christian Torp-Pedersen (Aalborg University, Denmark) point out that the reporting of odds ratios and not absolute risk in the current study limits its clinical perspective.
But they acknowledge that even a small increase “is a concern for public health”, given the widespread use of NSAIDs.
Only prescribed NSAIDs were assessed in the current study, but some over-the-counter NSAIDs are available at prescribed doses and may be used inappropriately, comment Giovanni et al.
Gislason and Torp-Pedersen say “a more restricted policy by regulatory authorities on the availability of NSAIDs and requirements for healthcare professionals providing advice on their use and potential harm is warranted.”
By Lucy Piper
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