Barcelona, Spain—Even short-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) appears to be linked to a first-time hospitalization for heart failure in specific patients with type 2 diabetes (T2D), according to new research.

The Danish-led study was presented at the European Society of Cardiology Congress 2022 in Barcelona, Spain.

"In our study, approximately one in six patients with type 2 diabetes claimed at least one NSAID prescription within one year," stated first author Anders Holt, MD, of Copenhagen University Hospital. "In general, we always recommend that patients consult their doctor before starting a new medication, and with results from this study, we hope to help doctors mitigate risk if prescribing NSAIDs."

Background information in the article pointed out that NSAID use has previously been associated with an increased risk of heart failure in the general population. Data has been lacking, however, in patients with T2D even though they have more than twice the likelihood of developing heart failure as those without diabetes.

The researchers focused on the association between short-term NSAID use and the risk of first-time heart failure hospitalization in a nationwide cohort of patients with T2D in Danish registries from 1998 to 2021. Excluded were patients with heart failure or a rheumatologic condition requiring long-term NSAID use.

The information was collected on prescriptions for oral NSAIDs (i.e., celecoxib, diclofenac, ibuprofen, and naproxen) filled prior to first-time heart failure hospitalization.

The study included 331,189 patients (44% female) with T2D and a mean age of 62 years.

The researchers noted that during the first year after inclusion in the study, 16% of patients claimed at least one NSAID prescription and 3% claimed at least three NSAID prescriptions. Ibuprofen was most commonly used (12.2%), followed by diclofenac (3.3%), naproxen (0.9%), and celecoxib (0.4%). During a median follow-up of 5.85 years, 23,308 patients were hospitalized with heart failure for the first time, according to the report.

The results indicated that NSAID use was associated with an elevated risk of first-time heart failure hospitalization, with an odds ratio (OR) of 1.43 (95% CI, 1.27-1.63). "When individual NSAIDs were analyzed separately, the risk of heart failure hospitalization 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," the researchers explained. "Celecoxib and naproxen were not associated with an increased risk, potentially due to the small proportion of claimed prescriptions."

The risk of heart failure with NSAID use also was analyzed in subgroups of patients. The study team identified no association in patients with normal glycated hemoglobin levels (below 48 mmol/mol), which indicates well-controlled diabetes.

On the other hand, strong associations were demonstrated in patients older than age 65 years; no association was found in those younger than age 65 years. The strongest association was found in very infrequent or new users of NSAIDs.

Although no data on OTC use of NSAIDs were included in the study, Dr. Hold stated, "This was a limitation but likely had no impact on the results since a previous report found that over-the-counter NSAIDs comprise a small proportion of total use."

"This was an observational study, and we cannot conclude that NSAIDs cause heart failure in patients with type 2 diabetes," Dr. Holt added. "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."

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