The Net Clinical Benefit of Fondaparinux vs LMWH in Chinese Non-ST-Segment Elevation Acute Coronary Syndrome Patients: the REFOCAS Nonrandomized Controlled Trial

Background and aims In Chinese patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS), it is essential to evaluate the net clinical benefit (NCB) of fondaparinux compared to low molecular weight heparin (LMWH) in NSTE-ACS patients with varying bleeding and ischemic risks. Methods This multicenter, prospective, open-label, real-world study enrolled 8066 adult patients undergoing non-emergency percutaneous coronary intervention (PCI) at 88 hospitals from July 2019 to July 2021. Patients received fondaparinux (2.5 mg/d) or LMWH (1 mg/kg, twice/day) were followed up within 6 months. The GRACE and CRUSADE scores were used to stratify the included patients. The primary outcome was the incidence of NCB event (all-cause death, reinfarction, nonfatal stroke, or BARC≥ type 2 bleeding) at 30 days. Results A total of 5430 patients received fondaparinux and 2636 received LMWH. The NCB outcome occurred in 136 patients (2.5%) receiving fondaparinux and in 110 patients (4.2%) receiving LMWH [HR=0.594 (95% CI: 0.462, 0.764), p<0.001]. The 30-day incidence of BARC≥2 bleeding was significantly lower in the fondaparinux group compared with the LMWH group [68 (1.3%) vs. 66 (2.5%), HR=0.498 (95% CI: 0.355, 0.699), p<0.001].Among patients with lower risk, defined by GRACE score≤140 and CRUSADE scores≤40, fondaparinux significantly reduced the incidence of MACE and BARC ≥ 2 bleeding. Fondaparinux decreased the risk of BARC≥2 bleeding across different risk groups, with absolute risk reductions (ARD) of -0.9% for CRUSADE score≤40, -3.0% for CRUSADE score>40, -1.2% for GRACE score≤140, and -1.7% for GRACE score>140, indicating a more pronounced protective effect in individuals at high bleeding risk. Conclusions In Chinese patients with NSTE-ACS, fondaparinux effectively diminished the incidence of the NCB event of 30 days compared with LMWH. Additionally, fondaparinux exhibited superior safety than LMWH in patients with high bleeding risk, consistently outperformed LMWH in terms of efficacy and safety in the low-risk group as well.