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NSAIDs increase risk of hospitalisation for heart failure

By Nicole MacKee
Current use of any NSAID is associated with a 19% increased risk of hospitalisation for heart failure, compared with past use, say researchers, but the risk varies between drug types and according to dose.

Professor David Brieger, Head of Coronary Care and Coronary Interventions at Sydney’s Concord Hospital, said the study reinforced Heart Foundation guideline recommendations for the use of NSAIDs.

‘We have all accepted that these drugs have risks in terms of exacerbating heart failure, hypertension and renal impairment, and that the patients who have left ventricular impairment and a history of heart failure are particularly at risk of these complications,’ said Professor Brieger, who is also the Editor-in-Chief of Cardiology Today.

Of the 23 traditional NSAIDs and four selective cyclo-oxygenase (COX)-2 inhibitors investigated, the researchers found that seven NSAIDs and two COX-2 inhibitors were linked with increased risk of hospitalisation for heart failure.

Higher rates of admission were found in patients who, in the preceding fortnight, had been prescribed diclofenac (odds ratio [OR], 1.19), ibuprofen (OR, 1.18), indomethacin (OR, 1.51), ketorolac (OR, 1.83), naproxen (OR, 1.16) or piroxicam (OR, 1.27), as well as the COX-2 inhibitor, etoricoxib (OR, 1.51).

Elevated heart failure risk was also found with nimesulide, which is not marketed in Australia, and the COX-2 inhibitor rofecoxib, which was withdrawn from the market internationally in 2004. The study found no evidence of increased risk of heart failure with celecoxib.

Data from five healthcare databases in the Netherlands, Italy, Germany and the UK were analysed in the nested case-control study published in the BMJ. Researchers identified 92,163 hospitalisations for heart failure in the decade to 2010, and these cases were matched with more than 8 million controls. The patients had a mean age of 77 years, and 45% of cases and controls were men.

The researchers identified a dose–response effect, with users on very high doses (≥2 defined daily dose equivalents) of diclofenac, indomethacin, piroxicam, etoricoxib and rofecoxib at more than twice the risk of heart failure compared with past users.

Professor Brieger said the finding reflected current practice to opt for the lowest possible dose. ‘Our guidelines currently say that we should avoid these drugs in patients with heart failure, and that’s sensible. But often patients do need some sort of analgesia – for an episode of arthritis that is particularly disabling or an injury – and, after considering safer drugs like paracetamol, NSAIDs may be considered, but at a low dose,’ he said.

He noted that in the BMJ study heart failure risk was at acceptable levels for all nine drugs when used at low doses (≤0.8 defined daily dose equivalents).

However, Professor Brieger advised caution in drawing clinical conclusions from administrative datasets.

‘There are huge challenges in taking enormous administrative datasets that have been created for other purposes, and harmonising them in the way that has been done here,’ he said.
BMJ 2016; 354: i4857.

Picture credit: © BSIP/Medical Images