Painkillers that can increase risk of heart failure

14th October 2016

Many commonly used nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of hospital admission for heart failure, a study of European national healthcare databases shows.

Use of any NSAID in the previous 14 days was associated with a 19% increased risk of hospital admission for heart failure compared with use more than six months before, researchers from the Safety of NSAIDS Project Consortium reported in the British Medical Journal (BMJ).

Dr Giovanni Corrao from the University of Milano-Bicocca in Italy and colleagues in the consortium said the increases were significant for the following drugs:

  • Diclofenac
  • Ibuprofen
  • Indomethacin
  • Ketorolac
  • Naproxen
  • Nimesulide
  • Piroxicam
  • Etoricoxib
  • Rofecoxib

The effects appeared dose-dependent. The risk of heart failure doubled for diclofenac, etoricoxib, indomethacin, piroxicam, and rofecoxib used at twice or more the recommended daily allowable dose.

But the researchers said: "Even medium doses of indomethacin and etoricoxib were associated with increased risk."

Dr Corrao's study included 92,163 heart failure hospital admissions who started NSAID treatment in 2000-2010 recorded on healthcare databases in the Netherlands, Italy, Germany and the UK.

The overall link between NSAIDs and heart failure has been known for over 20 years, and is likely related to the predilection of these drugs to cause retention of salt and water and increases in blood pressure, Dr Milton Packer, from the Baylor University Medical Centre in Dallas, told MedPage Today.

Notably, though, celecoxib was not associated with higher risk of heart failure hospital admission at commonly used, typically lower doses.

"The relative safety of celecoxib is also consistent with earlier reports," Dr Packer wrote. "The results of the upcoming PRECISION trial (a randomized trial of celecoxib versus naproxen on cardiovascular events) will be presented at the American Heart Association meeting in November. It will be interesting to see if the results of the trial confirm the findings of this observational study."

An editorial in BMJ criticised the study for not reporting absolute risk differences, which makes the findings harder to assess.

"Low risk patients might accept the small additional risk associated with treatment while higher risk patients might prefer to consider alternative treatments," wrote Dr Gunnar Gislason, from Copenhagen University Hospital, and Christian Torp-Pedersen, from Denmark's Aalborg University.

For patients who do need NSAID treatment, it is important to consider the different risk profiles of the individual drugs, they added. The selective COX-2 inhibitors, such as rofecoxib, and diclofenac had repeatedly been associated with higher heart risk, and therefore it seemed prudent to avoid them and consider lower risk naproxen at the lowest effective dose. While the FDA and other agencies have warned about potential risks of NSAIDs, their wide over-the-counter use fuels the common misconception that NSAIDs are harmless drugs that are safe for everyone, the report said. But even a small increase in cardiovascular risk should be a concern.

Cardiomyopathy UK support nurse Robert Hall said: ““We have known for several years that people with heart problems need to use NSAIDS with care. People who take these drugs every day should discuss this with their GP, as they need to be prescribed carefully. Where possible the lowest dose, over the shortest period of time, should be used”

For more details of the study, see here