Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention: REPLACE-2 randomized trial.
BACKGROUND
The direct thrombin inhibitor bivalirudin has been associated with better efficacy and less bleeding than heparin during coronary balloon angioplasty but has not been widely tested during contemporary percutaneous coronary intervention (PCI).


OBJECTIVE
To determine the efficacy of bivalirudin, with glycoprotein IIb/IIIa (Gp IIb/IIIa) inhibition on a provisional basis for complications during PCI, compared with heparin plus planned Gp IIb/IIIa blockade with regard to protection from periprocedural ischemic and hemorrhagic complications.


METHODS
The Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial, a randomized, double-blind, active-controlled trial conducted among 6010 patients undergoing urgent or elective PCI at 233 community or referral hospitals in 9 countries from October 2001 through August 2002.


METHODS
Patients were randomly assigned to receive intravenous bivalirudin (0.75-mg/kg bolus plus 1.75 mg/kg per hour for the duration of PCI), with provisional Gp IIb/IIIa inhibition (n = 2999), or heparin (65-U/kg bolus) with planned Gp IIb/IIIa inhibition (abciximab or eptifibatide) (n = 3011). Both groups received daily aspirin and a thienopyridine for at least 30 days after PCI.


METHODS
The primary composite end point was 30-day incidence of death, myocardial infarction, urgent repeat revascularization, or in-hospital major bleeding; the secondary composite end point was 30-day incidence of death, myocardial infarction, or urgent repeat revascularization.


RESULTS
Provisional Gp IIb/IIIa blockade was administered to 7.2% of patients in the bivalirudin group. By 30 days, the primary composite end point had occurred among 9.2% of patients in the bivalirudin group vs 10.0% of patients in the heparin-plus-Gp IIb/IIIa group (odds ratio, 0.92; 95% confidence interval, 0.77-1.09; P =.32). The secondary composite end point occurred in 7.6% of patients in the bivalirudin vs 7.1% of patients in the heparin-plus-Gp IIb/IIIa groups (odds ratio, 1.09; 95% confidence interval 0.90-1.32; P =.40). Prespecified statistical criteria for noninferiority to heparin plus Gp IIb/IIIa were satisfied for both end points. In-hospital major bleeding rates were significantly reduced by bivalirudin (2.4% vs 4.1%; P<.001).


CONCLUSIONS
Bivalirudin with provisional Gp IIb/IIIa blockade is statistically not inferior to heparin plus planned Gp IIb/IIIa blockade during contemporary PCI with regard to suppression of acute ischemic end points and is associated with less bleeding.
Lincoff
A Michael
AM
Department of Cardiovascular Medicine, Desk F25, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195, USA. lincofa@ccf.org
Bittl
John A
JA
Harrington
Robert A
RA
Feit
Frederick
F
Kleiman
Neal S
NS
Jackman
J Daniel
JD
Sarembock
Ian J
IJ
Cohen
David J
DJ
Spriggs
Douglas
D
Ebrahimi
Ramin
R
Keren
Gadi
G
Carr
Jeffrey
J
Cohen
Eric A
EA
Betriu
Amadeo
A
Desmet
Walter
W
Kereiakes
Dean J
DJ
Rutsch
Wolfgang
W
Wilcox
Robert G
RG
de Feyter
Pim J
PJ
Vahanian
Alec
A
Topol
Eric J
EJ
D000077284:Abciximab; D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000925:Anticoagulants / Q000627:therapeutic use*; D017225:Atherectomy, Coronary / Q000009:adverse effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000077542:Eptifibatide; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006470:Hemorrhage / Q000517:prevention & control; D006493:Heparin / Q000627:therapeutic use*; D006629:Hirudins / Q000031:analogs & derivatives*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use; D007431:Intraoperative Complications / Q000517:prevention & control*; D007511:Ischemia / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000627:therapeutic use*; D010455:Peptides / Q000627:therapeutic use; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000627:therapeutic use*; D015607:Stents / Q000009:adverse effects; D016019:Survival Analysis; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D005343:Fibrinolytic Agents; D006629:Hirudins; D007140:Immunoglobulin Fab Fragments; D010446:Peptide Fragments; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; D006493:Heparin; D000077542:Eptifibatide; C074619:bivalirudin; D000077284:Abciximab