title: Eptifibatide in peripheral vascular interventions: results of the Integrilin Reduces Inflammation in Peripheral Vascular Interventions (INFLAME) trial.
abstract: An acute inflammatory response occurs following percutaneous coronary and peripheral vascular interventions (PVI), partly mediated by platelet activation. Glycoprotein (GP) IIb-IIIa inhibitors might partially attenuate this inflammation rise in the coronary patient, but data in patients undergoing PVI are lacking. In the Integrilin Reduces Inflammation in Peripheral Vascular Interventions trial (INFLAME), we hypothesized that eptifibatide reduces the acute inflammatory responses following PVI. This is a single-center, randomized, open-label study of intravenous eptifibatide (180 micro/kg bolus x 2, 10 minutes apart, then 2 micro/kg/min infusion over 18 hours) and low-dose unfractionated heparin (60 Units per kg, target activated clotting time (ACT) 200-250 sec) [LDH+I group; n = 21] versus high-dose unfractionated heparin alone (100 Units per kg, target ACT 300-400 sec) [HDH group; n = 21] in patients undergoing iliac and infrainguinal interventions. The primary endpoints of the study were markers of inflammation (soluble CD-40L [sCD-40L], high-sensitivity C-reactive protein [hs-CRP] and interleukin-6 [IL-6]), thrombin generation (Fragment 1.2 [F1.2]), and fibrinogen measured at baseline and postrandomization. Markers were assayed at baseline, postdilatation at 30 minutes, 2 hours, 18 hours, 48 hours and 7 days. Mean platelet inhibition with eptifibatide was 98% (range 92-100%) using the Accumetrics Rapid Platelet Function Assay at 10 minutes after final bolus. After adjusting for baseline values, the mean +/- SE difference in sCD-40L (loge scale), hs-CRP and F1.2 between the LDH+I group and the HDH was not significant. Fibrinogen had significantly higher mean levels at 7 days for the LDH+I group (541.19 mg/dL versus 472.26 mg/dL; p-value = 0.024). IL-6 was more detectable in the LDH+I group compared to the HDH following intervention. We conclude that LDH+I combination did not reduce acute inflammatory responses as compared to HDH in patients undergoing peripheral vascular interventions.
authors.affiliation: Midwest Cardiovascular Research Foundation, Davenport, Iowa, USA.
authors.forename: Nicolas W
authors.initials: NW
authors.lastname: Shammas
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Dippel
authors.forename: Jon H
authors.initials: JH
authors.lastname: Lemke
authors.forename: Jon
authors.initials: J
authors.lastname: Robken
authors.forename: H Lester
authors.initials: HL
authors.lastname: Kirchner
authors.forename: Vickie
authors.initials: V
authors.lastname: Takes
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Kapalis
authors.forename: Theresa
authors.initials: T
authors.lastname: Palabrica
mesh_terms: D000368:Aged; D017541:Aneurysm, False / Q000139:chemically induced; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D004305:Dose-Response Relationship, Drug; D000077542:Eptifibatide; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016491:Peripheral Vascular Diseases / Q000097:blood / Q000188:drug therapy*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D013917:Thrombin / Q000378:metabolism; D013997:Time Factors; D014914:Whole Blood Coagulation Time
chemical_list: D000925:Anticoagulants; D015415:Biomarkers; D010455:Peptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D005340:Fibrinogen; D006493:Heparin; D013917:Thrombin; D000077542:Eptifibatide