Pharmacodynamic Effects of Vorapaxar in Patients With and Without Diabetes Mellitus

Figure 1. Study Design DAPT = dual antiplatelet therapy; DM = diabetes mellitus; MI = myocardial infarction; od = once daily; PAD = peripheral arterial disease; PD = pharmacodynamics.

Figure 2. Thrombin-Mediated Effects on Platelets and Systemically (A) Thrombin receptor activating peptide (TRAP)-induced maximal platelet aggregation (MPA%) measured by light transmittance aggregometry (LTA). The p values represent comparisons between the 2 groups at each time point. Error bars indicate SD. Intragroup comparisons for non-DM: Baseline versus DAPT + vorapaxar: mean difference = 72; 95% confidence interval (CI): 67 to 77; p < 0.001. Baseline versus clopidogrel + vorapaxar: mean difference = 72; 95% CI: 67 to 77; p < 0.001. DAPT + vorapaxar versus clopidogrel + vorapaxar: mean difference = 0.3; 95% CI: −1.6 to 0.72; p = 0.20. Intragroup comparisons for DM: Baseline versus DAPT + vorapaxar: mean difference = 73; 95% CI: 68 to 78; p < 0.001. Baseline versus clopidogrel + vorapaxar: mean difference = 73; 95% CI: 68 to 78; p < 0.001. DAPT + vorapaxar versus clopidogrel + vorapaxar: mean difference = 0; 95% CI: −0.35 to 0.35; p = 1.00. (B) Reaction time (R) measured by thromboelastography (TEG) using kaolin as agonist. The p values represent comparisons between the 2 groups at each time point. Error bars indicate SD. Intragroup comparisons for non-DM: Baseline versus DAPT +…

Figure 3. Markers of Platelet-Mediated Thrombogenicity CAT-induced maximal platelet aggregation (MPA%) measured by light transmittance aggregometry (LTA). The p values represent comparisons between the 2 groups at each time point. Error bars indicate SD. The agonist CAT is a combination of collagen-related peptide, adenosine diphosphate, and thrombin receptor activating peptide. Intragroup comparisons for non-DM: Baseline versus DAPT + vorapaxar: mean difference = 20; 95% CI: 15 to 25; p < 0.001. Baseline versus clopidogrel + vorapaxar: mean difference = 10; 95% CI: 3 to 16; p < 0.001. DAPT + vorapaxar versus clopidogrel + vorapaxar: mean difference = 10; 95% CI: 4 to 16; p = 0.003. Intragroup comparisons for DM: Baseline versus DAPT + vorapaxar: mean difference = 15; 95% CI: 7 to 23; p < 0.001. Baseline versus clopidogrel + vorapaxar: mean difference = 3; 95% CI: −6 to 11; p = 0.542. DAPT + vorapaxar versus clopidogrel + vorapaxar: mean difference = 12; 95% CI: 3 to 21; p = 0.010. Abbreviations as in Figure 1.

Figure 4. Markers of P2Y12 Signaling (A) Adenosine diphosphate (ADP)-induced maximal platelet aggregation (MPA%) measured by light transmittance aggregometry (LTA). The p values represent comparisons between the 2 groups at each time point. Error bars indicate SD. Intragroup comparisons for non-DM: Baseline versus DAPT + vorapaxar: p = 0.166. Baseline versus clopidogrel + vorapaxar: p = 0.811. DAPT + vorapaxar versus clopidogrel + vorapaxar: p = 0.269. Intragroup comparisons for DM: Baseline versus DAPT + vorapaxar: p = 0.837. Baseline versus clopidogrel + vorapaxar: mean difference = 12; 95% CI: 5 to 20; p = 0.002. DAPT + vorapaxar versus clopidogrel + vorapaxar: mean difference = 13; 95% CI: 5 to 20; p = 0.002. (B) Platelet reactivity index (PRI) measured by vasodilator-stimulated phosphoprotein (VASP). The p values represent comparisons between the 2 groups at each time point. Error bars indicate SD. Intragroup comparisons for non-DM: Baseline versus DAPT + vorapaxar: p = 0.063. Baseline versus clopidogrel + vorapaxar: p = 0.067. DAPT + vorapaxar versus clopidogrel + vorapaxar: p = 0.959. Intragroup comparisons for DM: Baseline versus DAPT + vorapaxar: p = 0.296. Baseline versus…

Figure 5. Markers Sensitive to Cyclooxygenase-1 Blockade (A) Arachidonic acid (AA)-induced maximal platelet aggregation (MPA%) measured by light transmittance aggregometry (LTA). The p values represent comparisons between the 2 groups at each time point. Error bars indicate SD. Intragroup comparisons for non-DM: Baseline versus DAPT + vorapaxar: mean difference = 2; 95% CI: −10 to 15; p = 0.734. Baseline versus clopidogrel + vorapaxar: mean difference = 42; 95% CI: 26 to 58; p < 0.001. DAPT + vorapaxar versus clopidogrel + vorapaxar: mean difference = 44; 95% CI: 28 to 60; p < 0.001. Intragroup comparisons for DM: Baseline versus DAPT + vorapaxar: mean difference = 9; 95% CI: −2 to 21; p = 0.108. Baseline versus clopidogrel + vorapaxar: mean difference = 40; 95% CI: 25 to 54; p < 0.001. DAPT + vorapaxar versus clopidogrel + vorapaxar: mean difference = 49; 95% CI: 36 to 63; p < 0.001. (B) Serum thromboxane B2 (TXB2). The p values represent comparisons between the 2 groups at each time point. Error bars indicate SD. Intragroup comparisons for non-DM: Baseline versus DAPT + vorapaxar: p = 0.545. Baseline versus clopidogrel + vorapaxar: p < 0.001. DAPT + vorapaxar versus clopidogrel +…