Non-ST Elevation Myocardial Infarction
Conditions
Keywords
Tirofiban, Resistance to antiplatelet agents
Brief summary
Investigators aimed to test the beneficial effect of tirofiban, a GPIIb/IIIa antagonist, for Non-ST-Elevation Acute Coronary Syndrome Patients who has high resistance to clopidogrel.
Detailed description
Some patients have a poor response to dual antiplatelet therapy (DAPT), and it can result in a poor prognosis after percutaneous coronary intervention (PCI). Devices like Ultegra Rapid Platelet Function Analyzer (VerifyNow®) enable us to quantify platelet reactivity quickly in the catheter laboratory. This means that the poor responders to DAPT can be identified, and the patients' outcomes can be improved by providing additional antiplatelet agents. Tirofiban, a GP IIb/IIIa inhibitor, is a potent antiplatelet agent which is recommended for Non-ST-Elevation acute coronary syndrome (NSTE-ACS) with high risk at presentation. However, its role is not clear for patients stabilized with standard medical treatment but with a poor responsiveness to DAPT. In this study, Investigators administered tirofiban on top of DAPT to patients with NSTE-ACS undergoing PCI who have a high platelet reactivity (HPR) identified by VerifyNow. To the best of our knowledge, there are few studies conducted with tirofiban for tailored antiplatelet therapy. Moreover, this is the first randomized study with NSTE-ACS patients for tailored use of tirofiban under the guidance of platelet reactivity.
Interventions
DRUGTirofiban
Sponsors
Seoul National University Bundang Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
19 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* diagnosed with NSTE-ACS who need PCI * loaded with aspirin and clopidogrel at least 6 h before the procedure
Exclusion criteria
* thrombocytopenia (platelet count \<100,000/μL) * history of hemorrhagic stroke * history of ischemic stroke in the recent 2 year * history of major surgery 6 months prior
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under Curve of Serial Cardiac Biomarkers | 0,6,12,18,24,30,36 hours | An area under the curve of serial levels of Troponin I and creatine kinase-MB isoenzyme during 36 hours |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Periprocedural Myonecrosis | 0,6,12,18,24,30,36 hours | Percentage of participants with periprocedural myonecrosis under the criteria described below. When the cardiac biomarkers before the procedure were within the 99th percentile upper reference limit (URL), more than a 5-fold elevation in the URL within 12 hours after percutaneous coronary intervention (PCI) was defined as periprocedural myonecrosis. If the cardiac biomarker level was already above the 99th percentile URL before the procedure and the trend was stationary or decreasing, a ≥20% increase compared to the previous level was considered periprocedural myonecrosis. If the trend was still increasing, the levels at the post-6 hour and 12-hour were compared to determine periprocedural myonecrosis. |
Participant flow
Recruitment details
Consecutively enrolled patients who are already stabilized with standard medical treatment and diagnosed with Non-ST elevation acute coronary syndrome (NSTE-ACS) at Seoul National University Bundang Hospital from February 2012 to October 2015
Participants by arm
| Arm | Count |
|---|---|
| Group A (High Platelet Reactivity - Tirofiban) Patients with high platelet reactivity unit (230 or higher) Tirofiban administered dose: 0.4 μg/kg/min continuous infusion for 30 min and then 0.10 μg/kg/min continuous infusion for 12 h
Tirofiban | 30 |
| Control C1 (High Platelet Reactivity - no Tirofiban) Patients with high platelet reactivity unit (230 or higher) Tirofiban was not administered | 30 |
| Control C2 (Low Platelet Reactivity - no Tirofiban) Patients with low platelet reactivity unit (less than 230) Tirofiban was not administered | 78 |
| Total | 138 |
Baseline characteristics
| Characteristic | Group A (High Platelet Reactivity - Tirofiban) | Control C1 (High Platelet Reactivity - no Tirofiban) | Control C2 (Low Platelet Reactivity - no Tirofiban) | Total |
|---|---|---|---|---|
| Age, Continuous | 70.0 years STANDARD_DEVIATION 12.8 | 64.5 years STANDARD_DEVIATION 12 | 62.9 years STANDARD_DEVIATION 10.1 | 64.8 years STANDARD_DEVIATION 11.4 |
| Sex: Female, Male Female | 13 Participants | 5 Participants | 11 Participants | 29 Participants |
| Sex: Female, Male Male | 17 Participants | 25 Participants | 67 Participants | 109 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 30 | 0 / 30 | 0 / 78 |
| other Total, other adverse events | 4 / 30 | 1 / 30 | 8 / 78 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 | 0 / 78 |
Outcome results
Primary
Area Under Curve of Serial Cardiac Biomarkers
An area under the curve of serial levels of Troponin I and creatine kinase-MB isoenzyme during 36 hours
Time frame: 0,6,12,18,24,30,36 hours
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Group A (High Platelet Reactivity - Tirofiban) | Area Under Curve of Serial Cardiac Biomarkers | Troponin I | 197.2 Hours*ng/ml |
| Group A (High Platelet Reactivity - Tirofiban) | Area Under Curve of Serial Cardiac Biomarkers | creatine kinase-MB isoenzyme | 252.5 Hours*ng/ml |
| Control C1 (High Platelet Reactivity - no Tirofiban) | Area Under Curve of Serial Cardiac Biomarkers | Troponin I | 38.0 Hours*ng/ml |
| Control C1 (High Platelet Reactivity - no Tirofiban) | Area Under Curve of Serial Cardiac Biomarkers | creatine kinase-MB isoenzyme | 92.7 Hours*ng/ml |
| Control C2 (Low Platelet Reactivity - no Tirofiban) | Area Under Curve of Serial Cardiac Biomarkers | Troponin I | 121.4 Hours*ng/ml |
| Control C2 (Low Platelet Reactivity - no Tirofiban) | Area Under Curve of Serial Cardiac Biomarkers | creatine kinase-MB isoenzyme | 185.6 Hours*ng/ml |
Secondary
Percentage of Participants With Periprocedural Myonecrosis
Percentage of participants with periprocedural myonecrosis under the criteria described below. When the cardiac biomarkers before the procedure were within the 99th percentile upper reference limit (URL), more than a 5-fold elevation in the URL within 12 hours after percutaneous coronary intervention (PCI) was defined as periprocedural myonecrosis. If the cardiac biomarker level was already above the 99th percentile URL before the procedure and the trend was stationary or decreasing, a ≥20% increase compared to the previous level was considered periprocedural myonecrosis. If the trend was still increasing, the levels at the post-6 hour and 12-hour were compared to determine periprocedural myonecrosis.
Time frame: 0,6,12,18,24,30,36 hours
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A (High Platelet Reactivity - Tirofiban) | Percentage of Participants With Periprocedural Myonecrosis | Troponin I | 16 Participants |
| Group A (High Platelet Reactivity - Tirofiban) | Percentage of Participants With Periprocedural Myonecrosis | creatine kinase-MB isoenzyme | 11 Participants |
| Control C1 (High Platelet Reactivity - no Tirofiban) | Percentage of Participants With Periprocedural Myonecrosis | Troponin I | 15 Participants |
| Control C1 (High Platelet Reactivity - no Tirofiban) | Percentage of Participants With Periprocedural Myonecrosis | creatine kinase-MB isoenzyme | 10 Participants |
| Control C2 (Low Platelet Reactivity - no Tirofiban) | Percentage of Participants With Periprocedural Myonecrosis | creatine kinase-MB isoenzyme | 25 Participants |
| Control C2 (Low Platelet Reactivity - no Tirofiban) | Percentage of Participants With Periprocedural Myonecrosis | Troponin I | 26 Participants |