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

J Am Coll Cardiol. 2006 Jun 20;47(12):2364-73. doi: 10.1016/j.jacc.2005.12.077.

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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Inflammation / prevention & control
  • Male
  • Middle Aged
  • Myocardial Infarction / therapy*
  • Myocardial Ischemia / etiology
  • Myocardial Ischemia / prevention & control
  • Peptide Fragments / therapeutic use*
  • Peptides / therapeutic use*
  • Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors*
  • Postoperative Complications / etiology
  • Postoperative Complications / prevention & control
  • Postoperative Hemorrhage / etiology
  • Postoperative Hemorrhage / prevention & control*
  • Recombinant Proteins / therapeutic use
  • Syndrome

Substances

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