Abstract 16503: Plasma Proteomics Reveal Greater Upregulation of Thrombomodulin in Patients Treated with Rivaroxaban Compared with Warfarin
Background: Plasma proteins mediate thrombogenesis, inflammation, endocardial injury and structural remodeling in atrial fibrillation (AF). Objectives: We hypothesized that anticoagulation with rivaroxaban, a direct factor Xa inhibitor, would differentially modulate biologically-relevant plasma proteins compared with warfarin, a multi-coagulation protein antagonist. Patients/
Methods: We performed unbiased liquid chromatography/tandem mass spectroscopy and candidate multiplexed protein immunoassays among Japanese subjects with non-valvular chronic AF who were randomly assigned to treatment with 24 weeks of rivaroxaban (n=93) or warfarin (n=94).
Results: Nine metaproteins -fibulin-1 (P=0.0033), vitronectin (P=0.0010), hemoglobin α (P=0.0012), apolipoprotein C-II (P=0.0017), complement C5 precursor (P=0.0026) and coagulation factor XIIIB (P=0.0032) apolipoprotein H (P=0.0023), coagulation factor XIIIA (P=0.0026) and insulin-like growth factor-binding protein complex acid labile subunit (P=0.0018) - were differentially expressed among patients with and without known clinical risk factors for stroke and bleeding in AF. Compared with warfarin, rivaroxaban treatment was associated with a greater increase in thrombomodulin (Δ 0.1 versus 0.3 pg/ml, P=0.0026) and a trend towards a reduction in matrix metalloproteinase-9 (Δ 2.2 versus -4.9 pg/ml, P=0.0757) over 24 weeks.
Conclusions: Plasma proteomics can identify protein subgroups associated with known stroke and bleeding risk phenotypes in an ethnically-homogenous AF population; these proteins deserve further exploration as mediators of stroke and bleeding risk. The greater upregulation of thrombomodulin among patients randomized to rivaroxaban is proof-of-principle that a pharmacoproteomic approach may identify novel effects of Xa inhibition.
- © 2012 by American Heart Association, Inc.