Abstract 2263: F1.2 Correlates with Ischemia by Holter Monitoring and is Suppressed by rNAPc2: an ANTHEM - TIMI 32 Biomarker Analysis
BACKGROUND: Coronary plaque rupture causes tissue factor (TF) exposure, and thrombin generation. An inactive peptide F1.2 is generated during thrombin formation and is an indirect measure of this process. ANTHEM-TIMI 32 was a dose ranging study of rNAPc2, a potent inhibitor of the TF/FVIIa complex which inhibits thrombin generation. We examined the relationship of F1.2 to ischemia by Holter monitoring.
METHODS: Patients ≤ 75y with NSTE-ACS < 48h and planned early cateterization were randomized (4:1) to IV rNAPc2 (1.5 to 10 ug/kg) or placebo q 48h . All pts had 3-lead Holters to assess for ischemia for up to 7d and measurement of F1.2 at baseline, 2– 6 h, and 48 h after study drug.
RESULTS: A total of 183, 179, and 90 subjects had evaluable Holters and a F1.2 level at baseline, 2– 6 h, and 48 h respectively. Baseline F1.2 levels tended to be higher in patients presenting with NSTEMI, those with diabetes, and smokers. At 2– 6 hours and 48 hours, F1.2 tended to be higher in patients with NSTEMI and lower in patients treated with rNAPc2. At baseline those with the lowest F1.2 levels (quartiles) tended to have less Holter ischemia (Q1 vs Q4: 19.6 vs 26.7%, p=NS), shorter durations of ischemia (19.4 vs 32.7 min, p=0.09) and a lesser ST-product (26.9 vs 64.1mm x min, p=0.02). At 2– 6 hours, lower levels of F1.2 were associated with less ischemia (figure⇓). Results were consistent in subjects treated with or without PCI.
CONCLUSIONS: Thrombin generation as detected by F1.2 was associated with more ischemia as by Holter monitoring in patients with NSTE-ACS. Based on F1.2, rNAPc2 effectively suppresses thrombin generation and may have the potential to favorably impact clinical outcomes in patients with ACS.