Fondaparinux versus enoxaparin in the contemporary management of non-ST-elevation acute coronary syndromes. Insights from a multicenter registry.

Background: Fondaparinux is thought to have the most favorable risk-benefit profile among all anticoagulants in non-ST-elevation acute coronary syndrome (NSTE-ACS). However, conflicting findings exist whether this holds true in current clinical practice. We aimed to assess the net clinical benefit of fondaparinux versus enoxaparin in the contemporary management of NSTE-ACS.

Methods: Analysis of prospective multicenter registry data of NSTE-ACS patients who received fondaparinux or enoxaparin from February 2015, through December 2017. Survival models within a competing risks framework including site-specific random effects, were used to assess the composite of clinically relevant bleedings and major adverse cardiovascular events at 30 days.

Results: Of 2094 patients, 1724 (82%) received enoxaparin and 370 (18%) fondaparinux. Both groups were comparable except for a lower prevalence of diabetes and renal impairment, and greater use of transradial approach in the fondaparinux group. Multivariate analysis revealed a net clinical benefit in favour of fondaparinux versus enoxaparin (Subhazard Ratio [SHR] 0.59; 95%CI 0.37-0.92), mainly driven by a reduction in bleeding (SHR 0.57; 95%CI 0.37-0.89). Exploratory analysis suggested greater reductions in bleeding with fondaparinux among patients undergoing transradial approach, revealing a significant interaction between treatment and vascular access on the multiplicative scale (P = 0.0056), but not on an additive scale (P = 0.457). Propensity-score-matching analysis yielded similar results.

Conclusions: In contemporary management of NSTE-ACS, fondaparinux seems to provide a favorable net clinical benefit compared with enoxaparin, primarily driven by a bleeding reduction. Effect modification on the safety profile of fondaparinux by the vascular access approach warrants further investigation.