Ticagrelor and Eptifibatide Bolus Versus Ticagrelor and Eptifibatide Bolus With 2-Hour Infusion in High-Risk Acute Coronary Syndromes Patients Undergoing Early Percutaneous Coronary Intervention

Abstract

Background: In patients with non-ST-segment elevation acute coronary syndromes, inhibition of platelet aggregation (IPA) with a potent P2Y12 inhibitor, ticagrelor, was inferior to tirofiban infusion at 2 hours, indicating that glycoprotein IIb/IIIa inhibitors are still needed. Ticagrelor and eptifibatide bolus only may maximally inhibit platelet aggregation and decrease bleeding, but IPA with ticagrelor and eptifibatide bolus versus 2-hour infusion is unknown.

Methods and results: A total of 70 P2Y12-naïve patients, with high-risk non-ST-segment elevation acute coronary syndromes, were randomized to ticagrelor and eptifibatide bolus (group 1) versus ticagrelor and eptifibatide bolus with 2-hour infusion (group 2). Levels of IPA with ADP, thrombin receptor-activating peptide, collagen, and high on-treatment platelet reactivity were measured by light transmission aggregometry at baseline and at 2, 6, and 24 hours after percutaneous coronary intervention in both groups. The primary end point, IPA with ADP 20 μmol/L at 2 hours, was 99.59±0.43% in group 1 versus 99.88±1.0% in group 2 (P<0.001 for noninferiority). High on-treatment platelet reactivity with ADP was zero at 2, 6, and 24 hours in both groups. IPA levels with ADP, thrombin receptor-activating peptide, and collagen were significantly higher at 2 and 6 hours than at 24 hours in both groups. Periprocedural myocardial infarction was not significantly different between the groups. Hemoglobin level was significantly less at 24 hours versus baseline in group 2 (13.35±1.8 versus 12.38±1.8 g/dL, respectively; P<0.01).

Conclusions: Ticagrelor and eptifibatide bolus maximally inhibited platelet aggregation at 2 hours, which was associated with no significant hemoglobin drop after percutaneous coronary intervention. This obviates the need for eptifibatide 2-hour infusion and might decrease bleeding complications.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01919723.

Keywords: antiplatelet therapy; eptifibatide; inhibition of platelet aggregation; ticagrelor.

© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Figures

Figure 1

Patient flow and study design. A, demonstrates the number of patients screened and randomized to 2 groups; (B) shows the study design and sampling schedule. Light transmission aggregometry (LTA) was performed at baseline (before administration of ticagrelor and eptifibatide bolus or 2‐hour infusion) and at 2, 6, and 24 hours using ADP, thrombin receptor activating peptide (TRAP), and collagen after the administration of the study drug. Ticagrelor and eptifibatide bolus or infusion were administrated just before percutaneous coronary intervention (PCI).

Figure 2

Platelet aggregation (PA) by light transmission aggregometry (LTA). At baseline and at 2, 6, and 24 hours after treatment, gray bars represent PA with ADP 20 μmol/L in the ticagrelor and eptifibatide group (group 1, T+E); red bars represent PA with ADP 20 μmol/L in the ticagrelor and eptifibatide bolus with 2‐hour infusion group (group 2, T+E bolus and 2‐hour infusion); green bars, PA with thrombin receptor‐activating peptide (TRAP) 20 μmol/L in the ticagrelor and eptifibatide group (group 1, T+E); and yellow bars, PA with TRAP 20 μmol/L in the ticagrelor and eptifibatide bolus with 2‐hour infusion group (group 2, T+E bolus and 2‐hour infusion). PA with ADP 20 μmol/L or TRAP 20 μmol/L was significantly higher at baseline than that at 2, 6, and 24 hours. PA with ADP or TRAP was significantly lower at 2 and 6 hours than that at 24 hours.

Figure 3

Inhibition of platelet aggregation (IPA) with ADP. A, IPA stimulated with ADP 5 μmol/L after treatment with ticagrelor and eptifibatide (T+E bolus) vs ticagrelor and eptifibatide bolus with 2‐hour infusion (T+E bolus and 2‐hour infusion). B, IPA stimulated with ADP 20 μmol/L after treatment with ticagrelor and eptifibatide (T+E) bolus vs ticagrelor and eptifibatide bolus with 2‐hour infusion (T+E bolus and 2‐hour infusion). In both groups (A and B), IPA levels were significantly higher at 2 and 6 hours than 24 hours.

Figure 4

Inhibition of platelet aggregation (IPA) with thrombin receptor activating peptide (TRAP). A, IPA with TRAP 10 μmol/L after treatment with ticagrelor and eptifibatide (T+E) bolus vs ticagrelor and eptifibatide bolus with 2‐hour infusion (T+E bolus and 2‐hour infusion). B, IPA with TRAP 20 μmol/L after treatment with ticagrelor and eptifibatide (T+E) bolus vs ticagrelor and eptifibatide bolus with 2‐hour infusion (T+E bolus and 2‐hour infusion). In both (A and B), IPA levels were significantly higher at 2 and 6 hours than 24 hours. IPA level was significantly higher with T+E bolus and 2‐hour infusion than with T+E at 6 hours.

Figure 5

Percentages of high on‐treatment platelet reactivity (HPR). A, percentages of HPR with ADP 5 μmol/L using the cut point >46%. At baseline, percentages of HPR were 89% and 79% (P=0.46). At 2, 6, and 24 hours, percentages of HPR were 0, indicating that ticagrelor and eptifibatide bolus or infusion completely blocked platelet reactivity stimulated with ADP 5 μmol/L. B, percentages of HPR with ADP 20 μmol/L using the cut point >59%. At baseline, percentages of HPR were 82% and 76% (P=0.87). At 2, 6, and 24 hours, percentages of HPR were 0, indicating that ticagrelor and eptifibatide bolus or infusion completely blocked platelet reactivity stimulated with ADP 20 μmol/L.