Acute Balloon Angioplasty vs. Traditional Early Invasive Treatment of Non-ST-Elevation Myocardial Infarction

Study Overview
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Brief Summary
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The purpose of this study is: A) To determine whether patients with a certain type of heart attack (NSTEMI) can be reliably diagnosed in an ambulance using telemedicine. This is mandatory if NSTEMI patients in the future are to be treated with acute balloon angioplasty (primary PCI). B) To evaluate whether primary PCI compared with the current regimen of initial medical stabilization and sub-acute PCI results in reduction of infarct-size in NSTEMI-patients.

Detailed Description
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Primary PCI versus Traditional Early Invasive Treatment of Patients presenting with NSTEMI Patients with NSTEMI are currently admitted for initial evaluation and stabilization at local hospitals. An intensive antithrombotic treatment is initiated and after 3 - 7 days of cooling-off the patients are referred to an invasive centre for coronary angiography and possibly PCI or CABG - this is known as the early invasive approach. Some of these patients represent a high-risk sub-group with occluded or sub-occluded coronary arteries who might benefit from very early revascularization. Study Aims To investigate if it is technically feasible to diagnose patients with NSTEMI in the pre-hospital setting and reroute them to an invasive heart centre for primary PCI in a timely manner. To estimate area at risk (AAR = the part of cardiac muscle tissue at risk of infarction) and final infarct size (FIS) in patients referred for primary PCI and patients undergoing the traditional early invasive treatment, respectively. To investigate whether Primary PCI in patients with NSTEMI results in a shorter duration of the primary admission, fewer rehospitalizations with reinfarction and acute heart failure and a briefer overall sick leave within a year from the index admission. Methods In this study 300 consecutive patients with symptoms, clinical signs and ECG changes (≥4mm cumulated or ≥ 2mm ST-segment depression (horizontal or descending) in two associated leads) suggesting significant NSTEMI are randomized for one of two strategies, either (A) usual early invasive treatment (coronary angiography and possibly PCI after 3 days) or (B) direct referral (rerouting) to primary PCI at an invasive heart centre (Skejby). All patients undergo myocardial perfusion imaging at admission for PCI and again after 30 days to estimate AAR, FIS and possible myocardial salvage. All patients undergo cardiac MRI on the 7th day after admission for determination of AAR and FIS. The study is a randomized controlled study; it has been approved by the local ethics committee. Primary outcome measures are specified above If the study confirms that it is possible to diagnose and re-route NSTEMI patients for primary PCI with an acceptable diagnostic accuracy, then a larger scale mortality study will be planned. Furthermore, the present study will provide valuable information regarding AAR and FIS in NSTEMI-patients which may be of value for planning larger-scale, scintigraphic studies and for the possible future use of a single MRI scan to determine AAR and FIS.

Official Title
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Acute Angioplasty (Primary PCI) Versus Traditional Early Invasive Treatment of Patients Presenting With NSTEMI (The Second Danish Non-ST-Elevation MI Trial - DaNSTEMI-2)

Conditions
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Myocardial Infarction

Intervention / Treatment
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* Procedure: Primary Percutaneous Coronary Intervention
* Procedure: Coronary angiography / Percutaneous coronary intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with symptoms and signs of NSTEMI and significant ECG changes (Either ≥4mm cumulated ST-segment depression (horizontal or descending), or ≥2mm ST-segment depression (horizontal or descending) in two associated leads)and/or patients with positive biomarkers for myocardial infarction (troponin T) measured in the ambulance (prehospital measurement of biomarkers). Age above 18 years. Tentative diagnosis made pre-hospitally. Exclusion Criteria: Severe mental or psychiatric disease (eg. psychosis, dementia, bipolar disorder or depression) as well as other conditions making it impossible to obtain informed consent. Prior CABG (Coronary artery bypass graft) operation. Patients with ST-depression presumed to be caused by tachycardia or cardiac hypertrophy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Primary PCI in patients with acute Non-STEMI | Procedure: Primary Percutaneous Coronary Intervention<br>* Coronary Angiography and PCI using standard protocols and guidelines. Contrast either Iomeron or Visipaque at the operators discretion. Equipment used for the PCI is determined at the operators discretion. All patients undergoing primary PCI receive 10.000 units of Heparin, 600 mg of Clopidogrel and a Glycoprotein IIb/IIIa inhibitor. Patients randomized to standard treatment receive 300 mg of Clopidogrel and 120IU/kg of Dalteparin b.i.d until revascularization. Glycoprotein IIb/IIIa inhibitors or thrombin inhibitors can be given as a supplement at the local hospital at the physicians discretion. All patients receive 300 mg of aspirin upon admission or diagnosis in the ambulance.<br>|
| Active Comparator: 2<br>Standard medical treatment and coronary angiography after 3 days in patients with Non-STEMI. | Procedure: Coronary angiography / Percutaneous coronary intervention<br>* Coronary Angiography and PCI using standard protocols and guidelines. Contrast either Iomeron or Visipaque at the operators discretion. Equipment used for the PCI is determined at the operators discretion. All patients undergoing primary PCI receive 10.000 units of Heparin, 600 mg of Clopidogrel and a Glycoprotein IIb/IIIa inhibitor. Patients randomized to standard treatment receive 300 mg of Clopidogrel and 120IU/kg of Dalteparin b.i.d until revascularization. Glycoprotein IIb/IIIa inhibitors or thrombin inhibitors can be given as a supplement at the local hospital at the physicians discretion. All patients receive 300 mg of aspirin upon admission or diagnosis in the ambulance.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Final infarct size in the two study groups determined by MR |  | On the 7th day after admission | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Scintigraphic Area-At-Risk and Final-Infarct-Size in patients in group A(immediate angioplasty) and group B(early invasive strategy) respectively. |  | At the time of coronary angiography and after 30 days | 
| Proportion of rerouted patients who are treated with primary PCI. |  | At index admission | 
| Proportion of patients randomized to immediate angioplasty actually undergoing primary PCI within 120 minutes from first contact to health services. |  | At index admission | 
| Number of readmissions in the two groups due to acute heart failure or reinfarction |  | 30 days and one year | 
| Total number of days admitted at hospital in relation to the index infarction in the two groups |  | At index admission | 
| Total number of days on sick-leave in the two groups |  | In relation to the index admission | 
| Evaluation of AAR/FIS obtained by MRI on the 7th day after admission compared to AAR and FIS obtained by myocardial perfusion imaging (scintigraphy). |  | At the time of coronary angiography, on the 7th day after admission and after 30 days respectively. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myocardial Infarction, Myocardial Ischemia, Myocardial Revascularization, Telemedicine, Percutaneous Transluminal Coronary Angioplasty