Safety Profile and Bleeding Complications of Fondaparinux Versus Enoxaparin in Non‐ST Elevation Acute Coronary Syndrome

Background Non-ST-elevation acute coronary syndrome (NSTE-ACS) remains a major contributor to morbidity and mortality worldwide. Optimal anticoagulation is critical for preventing complications, but the choice between fondaparinux and enoxaparin remains debated, particularly regarding bleeding and ischemic outcomes. The objective of this study was to compare the safety profile, bleeding complications, ischemic outcomes, mortality, and composite adverse events between fondaparinux and enoxaparin in NSTE-ACS patients in Bangladesh. Methods This prospective observational study enrolled 177 NSTE-ACS patients from Noakhali Medical College and Hospital, Bangladesh, between January and December 2022. Patients received either fondaparinux (n=87) or enoxaparin (n=90). Bleeding and ischemic events, mortality, and composite outcomes were assessed at baseline, 3-month, and 6-month follow-ups. Multivariable logistic regression was performed to evaluate predictors of composite outcomes. Results Total bleeding incidence was significantly lower in fondaparinux-treated patients (6.90% vs. 23.33%, p=0.002), notably during index hospitalization (4.60% vs. 17.78%, p=0.006). Fondaparinux significantly reduced myocardial infarction (3.45% vs. 14.44%, p=0.016), recurrent ischemia (11.49% vs. 24.44%, p=0.025), and hospitalization due to heart failure (4.60% vs. 14.44%, p=0.026). Mortality was lower with fondaparinux but not statistically significant (13.79% vs. 25.56%, p=0.050). The composite endpoint of mortality and ischemic events was significantly lower in fondaparinux-treated patients (20.69% vs. 40.00%, p=0.005). Multivariable analysis revealed fondaparinux as an independent protective factor against composite outcomes (OR=0.336, 95% CI: 0.166-0.683, p=0.003), with no significant predictive value found for age, sex, hypertension, diabetes, smoking, or time to intervention. Conclusions Fondaparinux demonstrates superior safety and effectiveness over enoxaparin in reducing bleeding complications and ischemic events among NSTE-ACS patients. These findings support its preferential use in resource-constrained clinical settings.