The effects of bivalirudin compared with those of unfractionated heparin plus eptifibatide on inflammation and thrombin generation and activity during coronary intervention

Objective: To characterize effects of bivalirudin compared with unfractionated heparin plus eptifibatide on inflammation, and thrombin generation and activity after percutaneous coronary intervention. Methods: We measured the concentration in blood of fibrinopeptide A, prothrombin fragment 1 + 2, soluble CD40 ligand, interleukin 1 receptor antagonist, interleukin 6, and high sensitivity C-reactive protein in 63 patients treated with aspirin and clopidogrel and undergoing elective percutaneous coronary intervention, who were randomized to treatment with either bivalirudin (n=34) or unfractionated heparin plus eptifibatide (n=29). Results: Neither generation nor activity of thrombin increased 10 min after percutaneous coronary intervention in patients randomized to bivalirudin or unfractionated heparin plus eptifibatide. However, prothrombin fragment 1 + 2 increased modestly and comparably in both groups after 1 day. Inflammation, reflected by concentrations of interleukin 6 and high sensitivity C-reactive protein in blood, increased similarly 1 day after percutaneous coronary intervention in patients treated with either regimen. In a subset of patients (n = 12 in each group) from whom blood was obtained 30 days after percutaneous coronary intervention, the concentration of high sensitivity C-reactive protein was lower in those who had been treated with bivalirudin (by 3.5 mg/l, P= 0.002). Conclusion The early effects on inflammation and thrombin generation and activity are similar after treatment with bivalirudin alone compared with unfractionated heparin plus eptifibatide in patients treated with aspirin and clopidogrel who are undergoing percutaneous coronary intervention for symptoms of stable angina. The decreased concentration of high sensitivity C-reactive protein seen 30 days after percutaneous coronary intervention in those treated with bivalirudin is consistent with greater attenuation of inflammation that may have contributed to the trend toward reduced mortality 1 year later in those treated with bivalirudin in REPLACE-2.