Short-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a first hospitalization for heart failure in patients with type 2 diabetes, according to research presented at the 2022 ESC Congress.
In our study, approximately one in six patients with type 2 diabetes claimed at least one NSAID prescription in one year. In general, we always recommend that patients consult their doctor before starting a new medication, and with the results of this study we hope to help doctors mitigate the risk if they prescribe NSAIDs.”
Dr. Anders Holt, first author, Copenhagen University Hospital, Denmark
The use of NSAIDs has previously been associated with an increased risk of heart failure in the general population, but there are no data in patients with type 2 diabetes. Since patients with type 2 diabetes have more than twice the more likely to develop heart failure than those without diabetes, NSAIDs could be even more harmful in this risk group.
This study investigated the association between short-term NSAID use and the risk of first-time heart failure hospitalization in a national cohort of patients with type 2 diabetes. The researchers used Danish registries to identify patients diagnosed of type 2 diabetes between 1998 and 2021. Patients with heart failure or a rheumatological condition requiring long-term use of NSAIDs were excluded. Information was collected on prescriptions for oral NSAIDs (celecoxib, diclofenac, ibuprofen, and naproxen) claimed before the first heart failure hospitalization. Using a case-crossover design in which each patient acted as his own control, we assessed associations between short-term NSAID use and risk of first-time heart failure hospitalization.
The study included 331,189 patients with type 2 diabetes. The average age was 62 years and 44% were women. 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 mean follow-up of 5.85 years, 23,308 patients were hospitalized for heart failure for the first time.
NSAID use was associated with an increased risk of first-time heart failure hospitalization, with an odds ratio (OR) of 1.43 (95% confidence interval). [CI] 1.27–1.63). When individual NSAIDs were analyzed separately, the risk of heart failure hospitalization was increased after 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 prescriptions claimed.
The researchers also looked at the risk of heart failure with NSAID use in subgroups of patients. No association was found in patients with normal glycated hemoglobin (HbA1c) levels (below 48 mmol/mol), indicating well-controlled diabetes. Strong associations were found in patients older than 65 years, while no association was found in those younger than 65 years. The strongest association was found in very infrequent or new users of NSAIDs.
Dr. Holt noted that data on over-the-counter NSAID use was not included in the study. But he said: “This was a limitation but probably had no impact on the results, as a previous report found that over-the-counter NSAIDs represent 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 considered heart disease when considering the use of these medications. Conversely, the data indicate that it may be safe to prescribe NSAIDs short-term for patients younger than 65 years of age with well-controlled diabetes.”
Source:
European Society of Cardiology