NSAID Use Linked to Increased Heart Failure Risk in Type 2 Diabetes

Anders Holt, MD

Short-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) could increase the likelihood of experiencing a first-time heart failure hospitalization among patients with type 2 diabetes, according to a new study presented at the European Society of Cardiology (ESC) Congress 2022.

With NSAIDs, including ibuprofen, among the most commonly used medications, results of the study, which indicate use was associated with a more than 40% increase in the likelihood of a first-time heart failure hospitalization, raise a red flag related to use of these agents in patients with type 2 diabetes.

“In our study, approximately one in six patients with type 2 diabetes claimed at least one NSAID prescription within one year,” said lead investigator Anders Holt, MD, of Copenhagen University Hospital, Denmark, in a statement from the ESC. ”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.”

Presented as part of the ESC Congress 2022, which is held in-person for the first time since 2019, the present study was designed by Holt and a team of colleagues from institutions in Denmark and United Kingdom to investigate associations between short-term NSAID use and risk of heart failure in the wake of recent data linking NSAID use to development of heart failure. With this in mind, investigators designed an observational study leveraging data from Danish registers to identify patients diagnosed with type 2 diabetes from 1998-2018. To mitigate confounding investigators using a case-crossover design where each patient acted as their own control to estimate associations between short-term NSAID use and the risk of first-time heart failure hospitalization.

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From their search investigates identified 331,189 patients with type 2 diabetes and without a history of heart failure or rheumatological conditions. This cohort had a mean age of 62 years, 44% were women, and 16% claimed at least 1 NSAID prescription, with 3% claiming 3 or more prescriptions. Overall, 12.2% reported use of ibuprofen, 3.3% used diclofenac, 0.9% used naproxen, and 0.4% use celecoxib. The follow-up lasted a median of 5.85 years and, during that period, 23,308 patients experienced a first-time heart failure hospitalization.

Upon analysis, results indicated NSAID use was associated with an elevated risk of first-time heart failure hospitalization within 120 days (OR, 1.43 [95% CI, 1.27-1.63]). When assessing individual NSAIDs, results indicated the risk of heart failure hospitalization was observed for use of diclofenac (OR, 1.48 [95% CI, 1.10-2.00]) and ibuprofen (OR, 1.46 [95% CI, 1.26-1.69]), but not with celecoxib and naproxen, which investigators noted could be a result of the small sample size for these NSAIDs. Investigators pointed out the association between NSAID use and risk of heart failure was not observed in patients with an HbA1cof 6.5% or less. However, strong associations were observed for those aged older than 65 years and among those considered very infrequent or new users of NSAIDs.

“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,” Holt added.

This study, “Risk of Heart Failure Following Short-Term Non-Steroidal Anti-Inflammatory Drug Use in Patients with Type 2 Diabetes,” was presented at ESC Congress 2022.