CLINICAL RESEARCH: CLINICAL TRIAL
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
C. Michael Gibson, MS, MD*,3,*,
David A. Morrow, MD, MPH*,
Sabina A. Murphy, MPH*,
Theresa M. Palabrica, MD ,1,
Lisa K. Jennings, PhD ,4,
Peter H. Stone, MD*,
Henry H. Lui, MD ,
Thomas Bulle, MD||,
Nasser Lakkis, MD¶,
Richard Kovach, MD#,
David J. Cohen, MD, MSC**,2,
Polly Fish, BS*,
Carolyn H. McCabe, BS*,
Eugene Braunwald, MD* for the TIMI Study Group
* TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts
Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts
University of Tennessee, Knoxville, Tennessee
APEX Cardiology, Jackson, Tennessee
|| Cardiovascular Associates, Kingsport, Tennessee
¶ Ben Taub Hospital, Houston, Texas
# Our Lady of Lourdes Medical Center, Camden, New Jersey
** Beth Israel Deaconess Medical Center, Boston, Massachusetts.
Manuscript received May 6, 2005;
revised manuscript received November 23, 2005,
accepted December 1, 2005.
* Reprint requests and correspondence: Dr. C. Michael Gibson, 350 Longwood Avenue, First Floor, Boston Massachusetts 02115. (Email: mgibson{at}timi.org).
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.
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Abbreviations and Acronyms
| | ACT = activated clotting time | | CK-MB = creatine kinase-myocardial band | | CTFC = corrected TIMI frame count | | GP = glycoprotein | | IL = interleukin | | IV = intravenous | | MI = myocardial infarction | | NSTEMI = non–ST-segment elevation myocardial infarction | | PCI = percutaneous coronary intervention | | TIMI = Thrombolysis In Myocardial Infarction | | TMPG = TIMI myocardial perfusion grade | | UFH = unfractionated heparin |
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