Anti-Inflammatory Medications May Elevate the Risk of HEART FAILURE in DIABETES PATIENTS
Nonsteroidal anti-inflammatory agents (NSAIDs) are commonly used for pain relief and inflammation reduction. However, they have been associated with fluid retention and endothelial dysfunction. Type 2 diabetes mellitus (T2DM) has also been linked to declining kidney function and subclinical cardiomyopathy.
Certain subgroups of patients, such as the elderly, those with uncontrolled diabetes, patients prescribed NSAIDs for the first time, and those already taking both a renin-angiotensin-system inhibitor (RASi) and a diuretic, may be at higher risk of complications associated with NSAIDs.
Therefore, this study determined whether short-term use of NSAIDs could lead to the development of heart failure (HF) in patients with T2DM.
Heart failure hospitalizations related to NSAIDs are often attributed to temporary fluid overload caused by the drugs' renal effects rather than worsening cardiac function. The severity of heart failure events related to NSAIDs may be less severe and potentially associated with better outcomes than other forms of heart failure.
The drugs may promote heart failure (HF) through direct effects on the heart via various proposed mechanisms, including vasoconstriction, induction of arrhythmias and heart fibrosis, subclinical inflammation, and blood pressure elevation. These mechanisms may contribute to the development or exacerbation of HF in patients who use NSAIDs, suggesting that the effects of these drugs on the heart may be multifactorial and not solely related to transient fluid overload.
The study utilized nationwide Danish registers to identify the patients diagnosed with type 2 diabetes mellitus (T2DM) between 1998 and 2021. It included patients without previous HF, rheumatic disease, or NSAID use within 120 days prior to T2DM diagnosis. The study included 331,189 patients with T2DM, with 44.2% being female and a median age of 62 years.
During follow-up, 23,308 patients were hospitalized with HF, and 16% of patients had at least 1 NSAID prescription within 1 year. The average age of these patients was 76 years, with 39% being women. These patients served as their own controls, and their NSAID exposures at two 28-day periods following the HF event were compared as the index and control periods, respectively. NSAID exposure was defined as obtaining a prescription for celecoxib, diclofenac, ibuprofen, or naproxen, which are NSAIDs primarily used in Denmark.
The primary outcome was the association between short-term use of NSAIDs and the risk of HF hospitalization in patients diagnosed with T2DM, as measured by odds ratios (ORs) with 95% confidence intervals (CIs). A case-crossover design with 28-day exposure windows was utilized to investigate this association.
Odds ratio for HF hospitalization associated with NSAID exposure within 28 days preceding the event
Overall patients
1.41
Patients exposed to NSAID along with both RASi and diuretics.
Patients with elevated hemoglobin A1c levels who received 0 to 1 antidiabetic drug 1.68
Patients who are 80 years or older 1.78
Patients with prior NSAID use
Association of HF hospitalization with different NSAIDs
The risk of HF hospitalization was significantly higher in patients exposed to celecoxib than other NSAIDs, while the risk was lower in patients exposed to Naproxen (Figure 1).
Based on the findings of this study, NSAIDs were commonly used and were linked to an increased risk of hospitalization for first-time heart failure in patients with type 2 diabetes.
The older patients, those with higher HbA1c levels, and those who were new users of NSAIDs appeared to be more vulnerable. These findings could guide physicians when prescribing NSAIDs to patients.
Key Takeaways:
Short-term NSAID use increases HF hospitalization risk in T2DM patients, especially older patients, those with higher HbA1c levels, and new users.
Physicians should weigh the benefits and risks when prescribing NSAIDs to T2DM patients, especially in high-risk subgroups.
More research is required to better understand the mechanisms underlying the association between NSAIDs and HF in T2DM patients.
Study limitations
Firstly, the study does not conclusively determine whether NSAID-associated heart failure (HF) is caused by transient fluid overload or direct cardiac effects, but it is probable that both factors play a role.
Secondly, the analysis has limitations in accurately examining whether the promotion of HF is a class effect of NSAIDs, which is significant in light of the differing effects of these drugs on cardiovascular risk.