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Ibuprofen and diclofenac are associated with an increased risk of heart failure hospitalisation in type 2 diabetes patients, according to new research presented at ESC Congress 2022.
Both ibuprofen and diclofenac are types of non-steroidal anti-inflammatory drugs (NSAIDs) used to relieve pain, reduce inflammation and bring down a high temperature.
NSAID use has previously been associated with an increased risk of heart failure in the general population2 but data are lacking in patients with type 2 diabetes.
Since type 2 diabetes patients are twice as likely to develop heart failure than those without the condition, the researchers set out to investigate whether there was an association between short-term NSAID use and the risk of first-time heart failure hospitalisation.
Type 2 diabetes patients twice as likely to develop heart failure than those without the condition
To do this, the researchers analysed data from more than 331,000 patients with type 2 diabetes. The data was taken from Danish registers between 1998 and 2021.
Patients with heart failure or a rheumatological condition requiring long-term NSAID use were excluded. Information was collected on prescriptions for oral NSAIDs (celecoxib, diclofenac, ibuprofen, and naproxen) claimed prior to first-time heart failure hospitalisation.
The study used a case-crossover design in which each patient acted as his or her own control. The researchers then used this data to determine whether there was an association between short-term NSAID use and the risk of first-time heart failure hospitalisation.
Celecoxib and naproxen were not associated with an increased risk of heart failure hospitalisation
During the first year after inclusion in the study, 16% of patients claimed at least one NSAID prescription while 3% claimed at least three prescriptions. Ibuprofen was used by 12.2% of patients, diclofenac by 3.3%, naproxen by 0.9%, and celecoxib by 0.4%.
During a median follow up of 5.85 years, 23,308 patients were hospitalised with heart failure for the first time.
NSAID use was associated with an elevated risk of first-time heart failure hospitalisation, with an odds ratio (OR) of 1.43 (95% confidence interval [CI] 1.27-1.63).
When individual NSAIDs were analysed separately, the risk of heart failure hospitalisation was increased following the use of diclofenac or ibuprofen, with corresponding ORs of 1.48 (95% CI 1.10-2.00) and 1.46 (95% CI 1.26-1.69), respectively.
Celecoxib and naproxen were not associated with an increased risk, potentially due to the small proportion of claimed prescriptions.
It may be safe to prescribe short-term NSAIDs for patients below 65 years of age
The researchers also analysed the risk of heart failure with NSAID use in subgroups of patients. They found no association in patients with well-controlled diabetes (those with normal glycated haemoglobin (HbA1c) levels).
Strong associations were also found in patients above the age of 65 and in very infrequent or new users of NSAIDs.
Dr Anders Holt of Copenhagen University Hospital, Denmark admits there were some limitations to the study, including that over-the-counter NSAIDs were not included in the study. However, he said this “likely had no impact on the results since a previous report found that over-the-counter NSAIDs comprise a small proportion of total use”.
He concluded: “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.
“On the contrary, the data indicate that it may be safe to prescribe short-term NSAIDs for patients below 65 years of age and those with well-controlled diabetes.”