Bivalirudin during primary PCI in acute myocardial infarction.
BACKGROUND
Treatment with the direct thrombin inhibitor bivalirudin, as compared with heparin plus glycoprotein IIb/IIIa inhibitors, results in similar suppression of ischemia while reducing hemorrhagic complications in patients with stable angina and non-ST-segment elevation acute coronary syndromes who are undergoing percutaneous coronary intervention (PCI). The safety and efficacy of bivalirudin in high-risk patients are unknown.


METHODS
We randomly assigned 3602 patients with ST-segment elevation myocardial infarction who presented within 12 hours after the onset of symptoms and who were undergoing primary PCI to treatment with heparin plus a glycoprotein IIb/IIIa inhibitor or to treatment with bivalirudin alone. The two primary end points of the study were major bleeding and combined adverse clinical events, defined as the combination of major bleeding or major adverse cardiovascular events, including death, reinfarction, target-vessel revascularization for ischemia, and stroke (hereinafter referred to as net adverse clinical events) within 30 days.


RESULTS
Anticoagulation with bivalirudin alone, as compared with heparin plus glycoprotein IIb/IIIa inhibitors, resulted in a reduced 30-day rate of net adverse clinical events (9.2% vs. 12.1%; relative risk, 0.76; 95% confidence interval [CI] 0.63 to 0.92; P=0.005), owing to a lower rate of major bleeding (4.9% vs. 8.3%; relative risk, 0.60; 95% CI, 0.46 to 0.77; P<0.001). There was an increased risk of acute stent thrombosis within 24 hours in the bivalirudin group, but no significant increase was present by 30 days. Treatment with bivalirudin alone, as compared with heparin plus glycoprotein IIb/IIIa inhibitors, resulted in significantly lower 30-day rates of death from cardiac causes (1.8% vs. 2.9%; relative risk, 0.62; 95% CI, 0.40 to 0.95; P=0.03) and death from all causes (2.1% vs. 3.1%; relative risk, 0.66; 95% CI, 0.44 to 1.00; P=0.047).


CONCLUSIONS
In patients with ST-segment elevation myocardial infarction who are undergoing primary PCI, anticoagulation with bivalirudin alone, as compared with heparin plus glycoprotein IIb/IIIa inhibitors, results in significantly reduced 30-day rates of major bleeding and net adverse clinical events. (ClinicalTrials.gov number, NCT00433966 [ClinicalTrials.gov].).
Stone
Gregg W
GW
Columbia University Medical Center and the Cardiovascular Research Foundation, New York, NY 10022, USA. gs2184@columbia.edu
Witzenbichler
Bernhard
B
Guagliumi
Giulio
G
Peruga
Jan Z
JZ
Brodie
Bruce R
BR
Dudek
Dariusz
D
Kornowski
Ran
R
Hartmann
Franz
F
Gersh
Bernard J
BJ
Pocock
Stuart J
SJ
Dangas
George
G
Wong
S Chiu
SC
Kirtane
Ajay J
AJ
Parise
Helen
H
Mehran
Roxana
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015906:Angioplasty, Balloon, Coronary; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use; D000991:Antithrombins / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004359:Drug Therapy, Combination; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000009:adverse effects / Q000627:therapeutic use; D006629:Hirudins / Q000009:adverse effects; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000401:mortality / Q000628:therapy*; D010446:Peptide Fragments / Q000009:adverse effects / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012008:Recurrence; D015607:Stents / Q000009:adverse effects; D020521:Stroke / Q000209:etiology; D013927:Thrombosis / Q000453:epidemiology / Q000209:etiology
D000925:Anticoagulants; D000991:Antithrombins; D006629:Hirudins; D010446:Peptide Fragments; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; D006493:Heparin; C074619:bivalirudin