Effects of Crushed Ticagrelor Versus Eptifibatide Bolus Plus Clopidogrel in Troponin-Negative Acute Coronary Syndrome Patients Undergoing Percutaneous Coronary Intervention: A Randomized Clinical Trial

Moazez J Marian, Hussein Abu Daya, Arka Chatterjee, Firas Al Solaiman, Mark F Sasse, William S Fonbah, Raymond W Workman, Brittany E Johnson, Sarah E Carlson, Brigitta C Brott, Sumanth D Prabhu, Massoud A Leesar, Moazez J Marian, Hussein Abu Daya, Arka Chatterjee, Firas Al Solaiman, Mark F Sasse, William S Fonbah, Raymond W Workman, Brittany E Johnson, Sarah E Carlson, Brigitta C Brott, Sumanth D Prabhu, Massoud A Leesar

Abstract

Background After a loading dose of ticagrelor, the rate of high on-treatment platelet reactivity remains elevated, which increases periprocedural myocardial infarction and injury. This indicates that faster platelet inhibition with crushed ticagrelor (CTIC) or eptifibatide is needed to reduce high on-treatment platelet reactivity. The efficacy of CTIC versus eptifibatide bolus plus clopidogrel is unknown. Methods and Results A total of 100 P2Y12 naïve, troponin-negative patients with acute coronary syndrome were randomized to CTIC (180 mg) versus eptifibatide bolus (180 μg/kg×2 intravenous boluses) plus clopidogrel (600 mg) at the time of percutaneous coronary intervention. High on-treatment platelet reactivity was markedly higher with CTIC versus eptifibatide bolus plus clopidogrel (42% versus 0%; P<0.001) at 30 minutes and persisted up to 2 hours (12% versus 0%; P=0.01, respectively). Platelet aggregation by adenosine diphosphate dropped faster from baseline with eptifibatide bolus plus clopidogrel versus CTIC (0.5 versus 2 hours, respectively) and was higher with CTIC versus eptifibatide bolus plus clopidogrel at 0.5, 2, and 4 hours after loading dose (53±12% versus 1.3±2%; 35±11% versus 0.34±1.0%; and 23±9% versus 3.5±2%, respectively; P<0.001). Eptifibatide bolus plus clopidogrel, but not CTIC, significantly inhibited platelet aggregation induced by thrombin-receptor activating peptide. Periprocedural myocardial infarction and injury was higher with CTIC versus eptifibatide bolus plus clopidogrel (48% versus 28%, respectively; P=0.035). Post-percutaneous coronary intervention hemoglobin levels were not different between groups. Conclusions Eptifibatide bolus plus clopidogrel led to faster and more potent platelet inhibition than CTIC and reduced periprocedural myocardial infarction and injury in troponin-negative acute coronary syndrome patients undergoing percutaneous coronary intervention, with no significant hemoglobin drop after percutaneous coronary intervention. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02925923.

Keywords: Unstable angina/ACS; crushed ticagrelor; eptifibatide bolus + clopidogrel; high on‐treatment platelet reactivity.

Figures

Figure 1
Figure 1
Study design. ACT indicates activated dotting time; cTnI, cardiac troponin I; Hb/HCT, hemoglobin/hematocrit; PCI, percutaneous coronary intervention.
Figure 2
Figure 2
Patient disposition. cTnI indicates cardiac troponin I; FFR, fractional flow reserve; INR, international normalized ratio; PCI, percutaneous coronary intervention.
Figure 3
Figure 3
High on‐treatment platelet reactivity (HPR). HPR levels were significantly higher with crushed ticagrelor vs clopidogrel plus eptifibatide bolus at 0.5 and 2 hours after loading dose.
Figure 4
Figure 4
Platelet aggregation (PA) levels induced by ADP. Crushed ticagrelor (CTIC) significantly dropped PA induced by ADP 20 μmol/L at 2, 4, and 24 hours but not at 30 minutes. Eptifibatide bolus plus clopidogrel significantly dropped PA at 0.5, 2, and 4 hours. PA dropped faster from baseline with eptifibatide bolus plus clopidogrel vs CTIC (0.5 vs 2 hours, respectively) and was significantly higher with CTIC vs eptifibatide bolus plus clopidogrel at 0.5, 2, and 4 hours after loading dose. PA level was significantly higher with clopidogrel plus eptifibatide bolus vs CTIC at 24 hours. NS indicates not significant.
Figure 5
Figure 5
Platelet aggregation levels induced by thrombin receptor‐activating peptide (TRAP). Crushed ticagrelor (CTIC) did not significantly affect platelet aggregation (PA) induced by TRAP 20 μmol/L at 0.5, 2, 4, and 24 hours. In contrast, eptifibatide bolus plus clopidogrel significantly reduced PA induced by TRAP at 0.5, 2, and 4 hours. Furthermore, PA was significantly higher with CTIC vs clopidogrel plus eptifibatide bolus at 0.5, 2, and 4 hours after loading dose. NS indicates not significant.
Figure 6
Figure 6
Distribution of troponin I levels after percutaneous coronary intervention (PCI). The rate of periprocedural myocardial infarction and injury (PMI) was significantly higher with crushed ticagrelor vs eptifibatide bolus plus clopidogrel. Bars indicate the mean levels of PMI with 95% CIs for each group. The dotted line indicates the limit of 195 ng/L (5×99th percentile of upper reference limit [URL] of troponin levels=39 ng/L).

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