Non ST Elevation Myocardial Infarction
Conditions
Brief summary
1. INTRODUCTION Through last couple of years the number of patients treated for acute coronary event without persistent ST segment elevation in ECG has been growing. This is probably an effect of improving diagnostics of myocardial infraction without persistent ST segment elevation in ECG, due to routine Troponin serum level evaluation and better primary prevention. This fact makes the search for the optimal treatment for patients with acute coronary event without persistent ST segment elevation in ECG, including both patients intended for pharmacological and invasive treatment percutaneous coronary intervention (PCI) or coronary artery byppass grafting (CABG). Patients undergoing invasive treatment for acute coronary event, have higher risk rate, than those with stabile angina pectoris. The authors of this study want to evaluate, whether the proportional use of platelet GP IIb/IIIa receptor antagonist - eptifibatide in patients undergoing CABG results in improvement of short-, and long time results in those patients. Eptifibatide ( Integrilin) a cyclic heptapeptide antagonist of the GP IIb/IIIa integrin receptor, is an intravenous antagonist with rapid onset and short half-life. 2. STUDY RATIONALE The notion acute coronary syndrome (ACS) includes several clinical situations, such a unstable coronary artery disease, non-Q wave myocardial infarction and Q wave myocardial infarction. On the basis of 12-lead ECG, patients with acute coronary syndrome (ACS) can be divided into two groups: with and without ST segment elevation. Another stratification factor in patients with ACS, especially these without ST elevation is evaluation of biochemical markers of myocardial necrosis, such as Troponins (TnI, TnT) and creatinine kinase isoenzymes (CK-MB). Serum concentrations of these markers allow to distinguish myocardial infarction (elevation of markers' concentration) from unstable coronary artery disease. All ACS have common etiopathogenesis which is plaque rupture, thrombus formation in the lumen of coronary artery. Platelets are the key factor in this process. Platelets by means of their collagen and von Willebrand factor glycoprotein receptors bind to damaged artery wall. Simultaneously many factors cause platelet activation, which leads to changes in their shape, release of intraplatelet components and activation of fibrinogen-binding glycoprotein receptors IIb/IIIa (GP IIb/IIIa). Activated form of GP IIb/IIIa binds to GP IIb/IIIa of another platelet by means of fibrinogen molecule. Fibrinogen molecules form stable bridges between platelets. This process is referred to as aggregation, and leads to clot formation, which is further stabilized by fibrine fibres. In this way the intravascular thrombus is formed, which after totally occluding the arterial lumen causes acute ischemia of the relevant region of myocardium and subsequently its infarction. The key role of GP IIa/IIIb in the process of platelet clot formation has important therapeutic consequences. By now several specific (direct) and non-specific (indirect) antagonists of GP IIb/IIIa have been developed. There are indirect antagonists as acetylsalicylic acid, ticlopidine and clopidogrel and direct antagonists as abciximab, tirofiban and eptifibatide Additionally also anticoagulants (heparin, LMWH - low molecular weight heparin) have antiplatelet properties by inhibiting thrombin production. Clinical studies performed all over the world have proven the efficacy and safety of three agents from the GP Iia/IIIb group: abciximab, tirofiban and eptifibatide. In several big clinical studies (EPIC, EPILOG, EPISTENT, ESPRIT, CAPTURE, PURSUIT, PRISM-PLUS, TACTICS-TIMI 18) the high efficacy of these drugs was showed in patients with ACS without ST segment elevation undergoing mainly percutaneous transluminal coronary angiography (PTCA) and stenting. The use of GP IIa/IIIb antagonists in this group of patients significantly reduces the death and myocardial infarction (MI) rate during early as well as late follow-up period. Moreover, last observations indicate, that the biggest benefit from such therapeutic strategy is observed in high risk patients; those with diabetes, high troponin levels and ECG changes. During last years, there is an increase in frequency of ACS without ST segment elevation. This is probably due to improved diagnostics of MI without ST elevation basing on routine troponin evaluation, but also thanks to better primary prevention. Therefore determining an optimal therapeutic strategy for patients with ACS without ST segment elevation remains a crucial issue. It concerns patients qualified to medical treatment as well as those qualified to invasive procedures (PTCA or CABG).
Interventions
DRUGEptifibatide
DRUGPlacebo
Sponsors
Medical University of Silesia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
21 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Subjects must have a typical anginal pain lasting at least 20 min., but no longer than 24h. * ECG confirming ischaemia * ST segment depression \>= 1,0 mm in at least 2 leads, or, * negative T waves \>= 2,0 mm in at least 2 leads. * Positive troponin I (TnI). * Subjects must demonstrate their willingness to participate in the study and comply with its procedures by signing a written informed consent and/or parent or legal guardian must have signed a written informed consent. * Subjects must be ≥ 21 year of age, of either sex and any race. * Women of childbearing potential (includes women who are less than 1 year postmenopausal and women who become sexually active) must be using an acceptable method of birth control (e.g., hormonal contraceptive, medically prescribed IUD - intrauterine device, condom in combination with spermicide) or be surgically sterilized (e.g., hysterectomy or tubal ligation). * Subjects must be free of any clinically significant disease that would interfere with study evaluations (see
Exclusion criteria
). * Subjects must understand and be able to adhere to the dosing and visit schedules, and agree to record concomitant medications and adverse events.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major Adverse Cardiac and Cerebrovascular Events (MACCE) | Up to 12 month | MACCE was defined as combined death, nonfatal myocardial infarction, cerebrovascular event (stroke) and the need for re-hospitalization due to recurrent ischemia up to 12 months follow-up |
Countries
Poland, United States
Participant flow
Recruitment details
Four clinical centers located within a radius of 50km of the reference center were selected for the study. From 2005 to 2010 a total of 140 patients presenting with NSTE-ACS not eligible for PCI were enrolled to the study. All CABG procedures were performed at 1st Department of Cardiac Surgery, Silesian Medical University in Katowice.
Participants by arm
| Arm | Count |
|---|---|
| Placebo/Control Group In the control group patients were given identical doses of acetylsalicylic acid and enoxaparin followed by a placebo infusion of saline in lieu of the GPIIb/IIIa inhibitor. | 68 |
| Eptifibatide In the treatment group patients were given a bolus of eptifibatide (Integrillin; 180µg/kg of body weight) and an intravenous infusion of 2 µg/kg/min followed by acetylsalicylic acid (150mg PO daily until the day of the procedure) and enoxaparin (1mg/kg SC - with the last dose 12 hours before surgery). The minimal and maximal periods of eptifibatide infusion were established at 12 and 48 hours respectively. | 72 |
| Total | 140 |
Baseline characteristics
| Characteristic | Eptifibatide | Placebo/Control Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 10 Participants | 21 Participants |
| Age, Categorical Between 18 and 65 years | 61 Participants | 58 Participants | 119 Participants |
| Age Continuous | 62.47 years STANDARD_DEVIATION 10.41 | 63.60 years STANDARD_DEVIATION 8.32 | 63.01 years STANDARD_DEVIATION 9.39 |
| Region of Enrollment Poland | 72 participants | 68 participants | 140 participants |
| Sex: Female, Male Female | 21 Participants | 19 Participants | 40 Participants |
| Sex: Female, Male Male | 51 Participants | 49 Participants | 100 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 72 | 9 / 68 |
| serious Total, serious adverse events | 2 / 72 | 7 / 68 |
Outcome results
Primary
Major Adverse Cardiac and Cerebrovascular Events (MACCE)
MACCE was defined as combined death, nonfatal myocardial infarction, cerebrovascular event (stroke) and the need for re-hospitalization due to recurrent ischemia up to 12 months follow-up
Time frame: Up to 12 month
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Major Adverse Cardiac and Cerebrovascular Events (MACCE) | 35.3 Percentage of study group |
| Eptifibatide | Major Adverse Cardiac and Cerebrovascular Events (MACCE) | 13.8 Percentage of study group |