Risk of heart failure following short-term non-steroidal anti-inflammatory drug use in patients with type 2 diabetes mellitus

Abstract

Background Fluid retention is a known but underappreciated side-effect of non-steroidal anti-inflammatory drug (NSAID) use. As type 2 diabetes mellitus (T2DM) has been linked to both subclinical cardiomyopathy and a decline in kidney function, short-term NSAID use could lead to subsequently development of heart failure (HF) due to aberrations in fluid balances. Purpose We investigated associations between short-term NSAID use and the risk of HF in a nationwide cohort of patients with T2DM. Methods Using nationwide Danish registers, we identified patients diagnosed with T2DM during 1998–2018. Follow-up began 120 days after first-time T2DM diagnosis among patients without prior heart failure or a rheumatological diagnosis indicating long-term NSAID use. To describe use of NSAID among patients with T2DM, we reported proportions of patients claiming at least 1, 2, 3 or 4 prescriptions of NSAID within one year of start of follow-up. We investigated associations between use of NSAIDs (celecoxib, diclofenac, ibuprofen and naproxen) and new-onset HF hospitalizations using a case-crossover design with 28-day exposure windows and reported odds ratios (OR) with 95% confidence intervals (CI). The case-crossover design uses each individual as his or her own control making it suitable to study the effect of short-term exposure on immediate events while mitigating unmeasured confounding. Sensitivity analyses using exposure windows of 14 and 42 days were performed as well. Results A total of 334,950 patients with T2DM was included (47.7% female, median age of 61 [interquartile range 50–70]). Celecoxib and naproxen were rarely used; on the contrary, prescriptions of diclofenac and ibuprofen were claimed at least once within one year from the beginning of follow-up by 4.9% and 15.5% of patients, respectively–0.9% and 2.7% claimed at least four prescriptions (Figure 1). The risk of new-onset HF hospitalization was increased following use of diclofenac or ibuprofen with corresponding ORs of 1.3 (95% CI 1.0 to 1.7) and 1.3 (95% CI 1.1 to 1.5) using 28-day exposure windows. An increased risk following use of celecoxib or naproxen was not found (Figure 2). Conclusion NSAIDs diclofenac and ibuprofen were both widely used and associated with an increased risk of new-onset HF hospitalization in patients with T2DM. This suggests a previously unknown and serious, clinically relevant concern of NSAID use in patients with T2DM. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Ib Mogens Kristiansens Almene FondHelsefonden

Causal relationship between aspirin consumption and heart failure: a Mendelian randomization study

“…8 Particularly noteworthy was the observed association among subgroups aged 80 years or older (OR: 1.78; 95% CI: 1.39-2.28). 8 However, other findings from ASPREE study 10 and ASCEND study 19 did not show enough evidence of a statistically significant effect of aspirin on incident heart failure in the study population. Although large cohort studies indicated a lack of significant benefit of aspirin for primary prevention in older individuals, 10,11 the clinical relevance of the association between aspirin use and the risk of heart failure was deemed to be limited based on the current studies.…”

“…The HOMAGE study firstly provided evidence reporting an elevated risk (adjusted hazard ratio [HR]: 1.26; 95% CI: 1.12–1.41) of heart failure among individuals at risk for heart failure who use aspirin 9 . In another large observational study involving 331 189 participants, the use of short‐term NSAIDs was shown to be associated with an increased risk of hospitalization due to heart failure (OR: 1.43; 95% CI: 1.27–1.63) 8 . Particularly noteworthy was the observed association among subgroups aged 80 years or older (OR: 1.78; 95% CI: 1.39–2.28) 8 .…”

“…7 A recent investigation revealed that the short-term utilization of nonsteroidal anti-inflammatory drugs (NSAIDS) in individuals with type 2 diabetes mellitus could result in the subsequent occurrence of heart failure. 8 Another study conducted by Mujaj et al 9 also concluded that there was an increased risk of heart failure among patients who take aspirin. The systematic review and meta-analysis have garnered significant attention within the medical community, shedding light on the potential association between aspirin use and elevated HF risk.…”

“…However, there has been ongoing controversy regarding the use of aspirin for primary prevention of cardiovascular events, 5,6 and aspirin is not recommended in the 2021 ESC prevention guidelines 7 . A recent investigation revealed that the short‐term utilization of nonsteroidal anti‐inflammatory drugs (NSAIDS) in individuals with type 2 diabetes mellitus could result in the subsequent occurrence of heart failure 8 . Another study conducted by Mujaj et al 9 also concluded that there was an increased risk of heart failure among patients who take aspirin.…”

Can Nonsteroidal Anti-Inflammatory Drugs Lead to First-Time Heart Failure in Patients with Diabetes Mellitus Type-2: Is There a Link?

“…A study recently presented at the 2022 Congress of the European Society of Cardiology (ESC) revealed that short-term NSAID use could potentially augment the chance of first-time HF in patients having T2DM [15]. A greater than 40% increase in the likelihood of hospitalization for first-time HF in patients who took NSAIDs, including ibuprofen, the most widely used drug, was observed.…”