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.

Abstract

OBJECTIVES:

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.

• Authors: C Michael Gibson, David A Morrow, Sabina A Murphy, Theresa M Palabrica, Lisa K Jennings, Peter H Stone, Henry H Lui, Thomas Bulle, Nasser Lakkis, Richard Kovach, David J Cohen, Polly Fish, Carolyn H McCabe, Eugene Braunwald, TIMI Study Group
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 47 Issue 12 Pg. 2364-73 (Jun 20 2006) ISSN: 1558-3597 [Electronic] United States
• PMID: 16781360 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antithrombins
• Enoxaparin
• Fibrinolytic Agents
• Hirudins
• Peptide Fragments
• Peptides
• Platelet Glycoprotein GPIIb-IIIa Complex
• Recombinant Proteins
• Heparin
• Eptifibatide
• bivalirudin

Topics

• Acute Disease
• Angina, Unstable (therapy)
• Angioplasty, Balloon, Coronary (adverse effects)
• Antithrombins (therapeutic use)
• Drug Therapy, Combination
• Enoxaparin (therapeutic use)
• Eptifibatide
• Female
• Fibrinolytic Agents (therapeutic use)
• Heparin (therapeutic use)
• Hirudins
• Humans
• Inflammation (etiology, prevention & control)
• Male
• Middle Aged
• Myocardial Infarction (therapy)
• Myocardial Ischemia (etiology, prevention & control)
• Peptide Fragments (therapeutic use)
• Peptides (therapeutic use)
• Platelet Glycoprotein GPIIb-IIIa Complex (antagonists & inhibitors)
• Postoperative Complications (etiology, prevention & control)
• Postoperative Hemorrhage (etiology, prevention & control)
• Recombinant Proteins (therapeutic use)
• Syndrome