NSAIDs and Risk for Heart Failure Hospitalization in Patients With Type 2 Diabetes

Patients with type 2 diabetes are at increased risk for hospitalization for heart failure up to 1 year following prescription of an NSAID.

Short-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) among patients with type 2 diabetes mellitus (T2DM) is associated with a higher risk for hospitalization for heart failure (HF), according to a study in the Journal of the American College of Cardiology.

Researchers hypothesized that NSAID use was prevalent in patients with T2DM and that even short-term use of NSAIDs was linked to an elevated risk of first-time HF hospitalization.

The analysis included data from Danish nationwide health registers for patients aged 18 to 100 years who were diagnosed with diabetes mellitus or initiated antidiabetic treatment in 1998 to 2021. Follow-up began 120 days after T2DM diagnosis, and the patients were followed until first-time HF hospitalization, death, or December 31, 2021, whichever came first.

The primary exposure was a claimed prescription of celecoxib, diclofenac, ibuprofen, or naproxen, and the investigators reported proportions of patients who claimed up to 4 prescriptions within 1 year from the start of follow-up. In the case-crossover analyses, the participants were considered exposed if an NSAID prescription was claimed within 28 days before the initial HF hospitalization.

Individual risk assessment is advised if prescribing NSAIDs for patients with T2DM.

The cohort included 331,189 patients diagnosed with T2DM (median age, 62 years [IQR, 52-71 years]; 44.2% women) in the study period. During the first year, 16% of patients claimed 1 or more NSAID prescriptions (ibuprofen, 12.2%; diclofenac, 3.3%; naproxen, 0.9%; celecoxib, 0.4%), and 3% claimed 3 or more prescriptions within a year.

A total of 23,308 patients were hospitalized with first-time HF during the follow-up (median age, 76 years [IQR, 68-83 years]; 39.3% women), and the median time to the event was 5.9 years (IQR, 2.6-10.2 years). With use of the case-crossover design, the association of first-time HF to previous NSAID exposure showed an increased risk. The odds ratio (OR) for risk for HF hospitalization with any NSAID in the 28-day exposure window was 1.43 (95% CI, 1.27-1.63). It was 1.41 (95% CI, 1.20-1.65) in the 14-day exposure window and 1.36 (95% CI, 1.22-1.53) in the 42-day exposure window. The associations were comparable for diclofenac and ibuprofen, and analyses for celecoxib and naproxen demonstrated statistically insignificant results, with few events available to assess.

Stronger associations with increased ORs occurred in subgroups of participants aged 65 years or older, and no association was observed in patients aged younger than 65 years. The strongest association was in participants without a previous claimed prescription of NSAIDs (OR, 2.71; 95% CI, 1.78-4.23). For patients with increased hemoglobin (Hb) A1c levels of 48 mmol/mol or higher and treated with 0 to 1 antidiabetic drug, the OR was 1.68 (95% CI, 1.00-2.88).

All-cause mortality after the initial HF hospitalization was reduced in patients exposed to NSAIDs compared with those not discordantly exposed to NSAIDs before HF hospitalization, with a 1-year standardized absolute risk difference (ARD) of -2.9% (95% CI, -5.3% to -0.4%), a 3-year ARD of -3.7% (95% CI, -6.9% to -0.5%), and a 5-year ARD of -3.9% (95% CI, -7.3% to -0.5%).

Among several limitations,misclassification may have occurred and undiagnosed ischemic heart disease or first-time ischemic heart disease between the control and index period could have introduced confounding and protopathic bias. Also, association does not imply causation, and the case-crossover design did not allow for an interpretable stratification of NSAID dosage.

“An elevated risk of HF was found when relating short-term NSAID use and first-time HF hospitalization using a self-controlled design with advanced age, elevated HbA1c levels, and no previous use of NSAIDs most strongly associated with first-time HF,” the study authors wrote. “Interestingly, the prognosis following incident HF for both NSAID-exposed and nonexposed was comparable. Individual risk assessment is advised if prescribing NSAIDs for patients with T2DM.”

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

This article originally appeared on The Cardiology Advisor


Holt A, Strange JE, Nouhravesh N, et al. Heart failure following anti-inflammatory medications in patients with type 2 diabetes mellitus. J Am Coll Cardiol. Published online April 18, 2023. doi: 10.1016/j.jacc.2023.02.027