Popular Medicines Including Ibuprofen Have Been Linked to Heart Failure in Diabetics

Researchers Discover New Side Effects of Non-Steroidal Anti-Inflammatory Drugs

According to a study presented at ESC Congress 2022, short-term use of non-steroidal anti-inflammatory drugs (NSAIDs) is linked to a first-time hospitalization for heart failure in individuals with type 2 diabetes.

NSAIDs are the most common form of anti-inflammatory medication.  The most popular NSAIDs include aspirin, ibuprofen (often known as Advil), and naproxen (known by the brand name Aleve and Naprosyn). However, despite their widespread use, these drugs can have side effects.

“In our study, approximately one in six patients with type 2 diabetes claimed at least one NSAID prescription within one year,” said first author Dr. Anders Holt of Copenhagen University Hospital, Denmark. ”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.

Elevated Risk of Heart Failure with NSAID Use

In the general population, NSAID usage has been linked to an increased risk of heart failure, however, data are lacking for patients with type 2 diabetes.  NSAIDs may be significantly more harmful in people with type 2 diabetes since they are more likely to experience heart failure than those without the condition.

This research looked at the relationship between short-term NSAID usage and the incidence of first-time heart failure hospitalization in a nationwide cohort of type 2 diabetes patients. The researchers analyzed Danish registries to identify people with type 2 diabetes diagnosed between 1998 and 2021. Patients with heart failure or a rheumatological condition that necessitated long-term NSAID treatment were not eligible.

Prior to the first heart failure hospitalization, information on prescriptions for oral NSAIDs (celecoxib, diclofenac, ibuprofen, and naproxen) was gathered. The links between short-term NSAID usage and the likelihood of first-time heart failure hospitalization were analyzed using a case-crossover approach in which each patient served as his or her own control.

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 median follow-up of 5.85 years, 23,308 patients were hospitalized with heart failure for the first time.

Increased Risk with Diclofenac and Ibuprofen

NSAID use was associated with an elevated 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 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.

The researchers also analyzed 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), which indicates well-controlled diabetes. Strong associations were found in patients above 65 years of age, while no association was found in those below 65 years of age. The strongest association was found in very infrequent or new users of NSAIDs.

Dr. Holt noted that data on over-the-counter use of NSAIDs were not included in the study. But he said: “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.”

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.”

Meeting: ESC Congress 2022

Funders: Ib Mogens Kristiansens Almene Fond, Helsefonden, Snedkermester Sophus Jacobsen og hustru Astrid Jacobsen Fond, Marie og M.B. Richters Fond, Dagmar Marshalls Fond, and the Danish Heart Foundation. None of the funders has had any influence on the conduction of this study.

All authors declare no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years, and no other relationships or activities that could appear to have influenced the submitted work.

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