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

Dear Editor, Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed drugs; however, they can lead to potential adverse effects [1]. The detrimental association between NSAIDs (apart from aspirin) usage and the peril to cardiac health has been documented profoundly in the literature [2–7]. The possible mechanism behind this adverse relationship can be due to an imbalance in the levels of prostaglandin E2 and vasodilatory prostacyclin compared to those of vasoconstrictive thromboxane A2, established due to NSAID usage targeting the endothelium and eventually leading to thrombus formation [8, 9]. Unlike other NSAIDs, aspirin irreversibly inhibits COX-1, leading to a reduction in thromboxane A2 and clot formation, while not significantly impacting vasodilatory prostaglandins and at low doses, this provides a cardioprotective effect [2]. NSAIDs are further known to exacerbate heart failure (HF) through increased salt and water retention [10–12]. A study conducted by Page and Henry [13] evaluated the hospitalization risk of HF for patients on NSAIDs. A relative risk of 2.1 was found in patients taking NSAIDs compared to nonusers. According to this study, NSAIDs use might contribute to 19% of newly diagnosed congestive HF cases. A study by Mamdani et al. [14] compared the hospitalization risk for congestive HF for patients being managed with nonselective NSAIDs, coxibs, and controls. Patients taking rofecoxib showed the most significant risk (RR = 1.8, 95% confidence interval [CI] = 1.5–2.2). While those taking nonselective NSAIDs showed a relative risk of 1.4 (95% CI = 1.0–1.9). These studies demonstrate that NSAIDs can cause as well as exacerbate preexisting HF. However, there is very limited data available that can relate to patients with first-time cardiac failure prescribed NSAIDs having T2DM. 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. According to the statement from ESC, lead investigator Anders Holt, MD, stated that almost 1 in 6 patients with T2DM in their study had usage of at least one NSAID for 1 year. Holt and a team of colleagues from institutions in Denmark and the United Kingdom designed this study as an observational one using data from Danish registers to find patients suffering with DM from 1998 to 2018. Investigators used a case-crossover method where the