Non-steroidal anti-inflammatory drugs linked with heart failure in patients with diabetes

People with type 2 diabetes who take non-steroidal anti-inflammatory drugs (NSAIDs) for short-term pain relief could have a 43% higher risk of developing heart failure than if they had not taken them, a study has found.

The findings, from a Danish registry study, are due to be presented at the European Society of Cardiology (ESC) Congress on 26 August 2022.

Researchers at Copenhagen University Hospital looked at data of 331,189 people with type 2 diabetes in Denmark from 1998 to 2021. Over a follow-up period averaging 5.8 years, 23,308 of the people identified (7%) were admitted to hospital with heart failure for the first time.

The researchers looked for an association between hospitalisation with heart failure and short-term prescription of oral NSAIDs (celecoxib, diclofenac, ibuprofen and naproxen). NSAIDs were frequently prescribed, with 16% of patients receiving at least one NSAID prescription during the first year of inclusion in the study. Diclofenac and ibuprofen were the most commonly prescribed NSAIDs.

The researchers found that NSAID use in any period was linked with a 43% increased risk of subsequent hospitalisation for heart failure (odds ratio (OR) 1.43, 95% confidence interval (CI) 1.27 to 1.63).

The risk was highest for ibuprofen (OR 1.46, 95% CI 1.26 to 1.69) and diclofenac (OR 1.48, 95% CI 1.10 to 2). The researchers found no increased risk with celecoxib or naproxen, but this may be because there were far fewer prescriptions for these drugs.

Commenting on the study, Sotiris Antoniou, head of pharmacy at St Bartholomew’s Hospital in London, said: “Whilst NSAIDs association with heart failure has been well reported, this new data, albeit from registry, reiterates the high risk of heart failure in patients with type 2 diabetes mellitus (T2DM).”

He added that heart failure was often under-diagnosed in this population, although “we are recognising that heart failure is one of the first complications to manifest in people with T2DM”. Pharmacists needed to be aware of the symptoms of heart failure when dispensing NSAIDS and ask questions about symptoms, he said.

“The key message for pharmacists in supplying NSAIDs, whether [over the counter] or prescribed, is the recognition of its association with heart failure, in particular at-risk populations for those over 65 years of age and now T2DM, and to not be afraid in asking questions related to heart failure symptoms such as shortness of breath, swelling around ankles, number of pillows required to help sleep, and how far they can walk before getting short of breath that may help assess suitability of NSAID supply,” he added.

The study did not include use of over-the-counter NSAIDs. Previous studies have found a link between NSAID use and heart failure in the general population, but this study suggests people with type 2 diabetes may be more likely to be adversely affected.

Lead researcher Anders Holt, from Copenhagen University Hospital, said in a press release: “This was an observational study and we cannot conclude that NSAIDS cause heart failure in patients with type 2 diabetes. However, the results suggest that a potential increased risk of heart failure should be taken into account when considering the use of these medications.”

The study also analysed sub-groups and found that the links were stronger for people aged over 65 years, and no link was found for people with normal HbA1c. People who were very infrequent or new users of NSAIDs had the strongest link.

The European Society of Cardiology Congress 2022 takes place in Barcelona on 26–29 August 2022.