A randomized trial to evaluate the relative protection against post-percutaneous coronary intervention microvascular dysfunction, ischemia, and inflammation among antiplatelet and antithrombotic agents: the PROTECT-TIMI-30 trial.
OBJECTIVE
The goal of this study was to evaluate glycoprotein IIb/IIIa inhibition with eptifibatide when administered with indirect thrombin inhibition as compared with monotherapy with direct thrombin inhibition with bivalirudin among patients with non-ST-segment elevation acute coronary syndromes (ACS).


BACKGROUND
The optimal combination of antiplatelet and antithrombin regimens that maximizes efficacy and minimizes bleeding among patients with non-ST-segment elevation ACS undergoing percutaneous coronary intervention (PCI) is unclear.


METHODS
A total of 857 patients with non-ST-segment elevation ACS were assigned randomly to eptifibatide + reduced dose unfractionated heparin (n = 298), eptifibatide + reduced-dose enoxaparin (n = 275), or bivalirudin monotherapy (n = 284).


RESULTS
Among angiographically evaluable patients (n = 754), the primary end point of post-PCI coronary flow reserve was significantly greater with bivalirudin (1.43 vs. 1.33 for pooled eptifibatide arms, p = 0.036). Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion grade more often was normal with eptifibatide treatment compared with bivalirudin (57.9% vs. 50.9%, p = 0.048). The duration of ischemia on continuous Holter monitoring after PCI was significantly longer among patients treated with bivalirudin (169 vs. 36 min, p = 0.013). There was no excess of TIMI major bleeding among patients treated with eptifibatide compared with bivalirudin (0.7%, n = 4 vs. 0%, p = NS), but TIMI minor bleeding was increased (2.5% vs. 0.4%, p = 0.027) as was transfusion (4.4% to 0.4%, p < 0.001).


CONCLUSIONS
Among moderate- to high-risk patients with ACS undergoing PCI, coronary flow reserve was greater with bivalirudin than eptifibatide. Eptifibatide improved myocardial perfusion and reduced the duration of post-PCI ischemia but was associated with higher minor bleeding and transfusion rates. Ischemic events and biomarkers for myonecrosis, inflammation, and thrombin generation did not differ between agents.
Gibson
C Michael
CM
TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA. mgibson@timi.org
Morrow
David A
DA
Murphy
Sabina A
SA
Palabrica
Theresa M
TM
Jennings
Lisa K
LK
Stone
Peter H
PH
Lui
Henry H
HH
Bulle
Thomas
T
Lakkis
Nasser
N
Kovach
Richard
R
Cohen
David J
DJ
Fish
Polly
P
McCabe
Carolyn H
CH
Braunwald
Eugene
E
D000208:Acute Disease; D000789:Angina, Unstable / Q000628:therapy*; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D000991:Antithrombins / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D017984:Enoxaparin / Q000627:therapeutic use*; D000077542:Eptifibatide; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006493:Heparin / Q000627:therapeutic use*; D006629:Hirudins; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000628:therapy*; D017202:Myocardial Ischemia / Q000209:etiology / Q000517:prevention & control; D010446:Peptide Fragments / Q000627:therapeutic use*; D010455:Peptides / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D011183:Postoperative Complications / Q000209:etiology / Q000517:prevention & control; D019106:Postoperative Hemorrhage / Q000209:etiology / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013577:Syndrome
D000991:Antithrombins; D017984:Enoxaparin; D005343:Fibrinolytic Agents; D006629:Hirudins; D010446:Peptide Fragments; D010455:Peptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; D006493:Heparin; D000077542:Eptifibatide; C074619:bivalirudin