Long-term efficacy of bivalirudin and provisional glycoprotein IIb/IIIa blockade vs heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary revascularization: REPLACE-2 randomized trial.
BACKGROUND
In the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial, bivalirudin with provisional glycoprotein IIb/IIIa (Gp IIb/IIIa) inhibition was found to be noninferior to heparin plus planned Gp IIb/IIIa blockade in the prevention of acute ischemic end points and was associated with significantly less bleeding by 30 days after percutaneous coronary intervention (PCI).


OBJECTIVE
To determine whether the efficacy of bivalirudin remains comparable with that of heparin plus Gp IIb/IIIa blockade over 6 months and 1 year.


METHODS
Follow-up study to 1 year of a randomized, double-blind 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 intravenously bivalirudin (0.75 mg/kg bolus, 1.75 mg/kg per hour for the duration of PCI), with provisional Gp IIb/IIIa inhibition, or to receive heparin (65 U/kg bolus), with planned Gp IIb/IIIa inhibition (abciximab or eptifibatide). Both groups received daily aspirin and a thienopyridine for at least 30 days after PCI.


METHODS
Incidence of death, myocardial infarction, or repeat revascularization by 6 months and death by 12 months after enrollment.


RESULTS
At 6 months, death occurred in 1.4% of patients in the heparin plus Gp IIb/IIIa group and in 1.0% of patients in the bivalirudin group (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.43-1.14; P =.15). Myocardial infarction occurred in 7.4% and 8.2% of patients, respectively (HR, 1.12; 95% CI, 0.93-1.34; P =.24), and repeat revascularization was required in 11.4% and 12.1% of patients, respectively (HR, 1.06; 95% CI, 0.91-1.23; P =.45). By 1 year, death occurred in 2.46% of patients treated with heparin plus Gp IIb/IIIa blockade and in 1.89% of patients treated with bivalirudin (HR, 0.78; 95% CI, 0.55-1.11; P =.16). Nonsignificant trends toward lower 1-year mortality with bivalirudin were present in all patient subgroups analyzed and were of greatest magnitude among high-risk patients.


CONCLUSIONS
Long-term clinical outcome with bivalirudin and provisional Gp IIb/IIIa blockade is comparable with that of heparin plus planned Gp IIb/IIIa inhibition during contemporary PCI.
Lincoff
A Michael
AM
Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. lincofa@ccf.org
Kleiman
Neal S
NS
Kereiakes
Dean J
DJ
Feit
Frederick
F
Bittl
John A
JA
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
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; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000925:Anticoagulants / Q000627:therapeutic use*; D004311:Double-Blind Method; D000077542:Eptifibatide; D005260:Female; D005500:Follow-Up Studies; D006493:Heparin / Q000627:therapeutic use*; D006629:Hirudins; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use; 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*; D016019:Survival Analysis; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D000925:Anticoagulants; 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