Comparison of bivalirudin versus heparin during percutaneous coronary intervention (the Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events [REPLACE]-1 trial).
To assess the efficacy of the direct thrombin inhibitor bivalirudin relative to heparin during contemporary coronary intervention, 1,056 patients who underwent elective or urgent revascularization were randomized in a large-scale pilot study to receive heparin (70 U/kg initial bolus) or bivalirudin (0.75 mg/kg bolus, 1.75 mg/kg/hour infusion during the procedure). All patients received aspirin; pretreatment with clopidogrel was encouraged, and glycoprotein (GP) IIb/IIIa blockade was at the physician's discretion. Stents were placed in 85% of patients; 72% received a GP IIb/IIIa inhibitor, and 56% were pretreated with clopidogrel. Activated clotting times were higher among patients randomized to bivalirudin than among those given heparin before device activation (median 359 vs 293 seconds, p <0.001). The composite efficacy end point of death, myocardial infarction, or repeat revascularization before hospital discharge or within 48 hours occurred in 5.6% and 6.9% of patients in the bivalirudin and heparin groups, respectively (p = 0.40). Major bleeding occurred in 2.1% versus 2.7% of patients randomized to bivalirudin or heparin, respectively (p = 0.52). This trial represents the largest prospective dataset of bivalirudin administered concomitantly with planned GP IIb/IIIa blockade and provides evidence of the safety and efficacy of this combined antithrombotic approach.
Lincoff
A Michael
AM
Cleveland Clinic Foundation, Cleveland, Ohio, USA. lincofa@ccf.org
Bittl
John A
JA
Kleiman
Neal S
NS
Sarembock
Ian J
IJ
Jackman
J Daniel
JD
Mehta
Sameer
S
Tannenbaum
Mark A
MA
Niederman
Alan L
AL
Bachinsky
William B
WB
Tift-Mann
J
J
Parker
H Graham
HG
Kereiakes
Dean J
DJ
Harrington
Robert A
RA
Feit
Frederick
F
Maierson
Elizabeth S
ES
Chew
Derek P
DP
Topol
Eric J
EJ
D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D000991:Antithrombins / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006493:Heparin / Q000009:adverse effects / Q000627:therapeutic use*; D006629:Hirudins / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D007430:Intraoperative Care; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000009:adverse effects / Q000627:therapeutic use*; D010865:Pilot Projects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000627:therapeutic use; D011183:Postoperative Complications / Q000209:etiology / Q000401:mortality; D019106:Postoperative Hemorrhage / Q000139:chemically induced; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D014914:Whole Blood Coagulation Time
D000925:Anticoagulants; D000991:Antithrombins; D006629:Hirudins; D010446:Peptide Fragments; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; D006493:Heparin; C074619:bivalirudin