Occluded Artery Trial (OAT)

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether opening an occluded infarcted artery 3-28 days after an acute myocardial infarction in high-risk asymptomatic patients reduces the composite endpoint of mortality, recurrent myocardial infarction, and hospitalization for class IV congestive heart failure over an average 2.9-year follow-up with extended follow up for an average of six years. Long term follow-up of patients were completed in March 2010. Final collection of all regulatory documentation was completed June 2011.

Detailed Description
-----------------
BACKGROUND: The benefits of establishing early coronary reperfusion in acute myocardial infarction (MI) have now been unequivocally established. However, current pharmacologic strategies fail to achieve effective reperfusion in 30 percent or more of patients, and many patients with occluded infarct arteries do not meet current criteria for use of these agents. Early angioplasty, an effective reperfusion method, is available to a small proportion of potentially eligible US acute MI patients. Hence a substantial number of acute MI patients pass the time when reperfusion therapy has any documented benefit (12 - 24 hours) with a persistently closed infarct vessel. Several lines of experimental and clinical evidence suggest that late reperfusion of these patients could provide clinically significant reductions in mortality and morbidity. DESIGN NARRATIVE: Multicenter, randomized, controlled. Patients at 217 clinical sites in the United States, Canada and Internationally were randomly allocated to two treatment arms over five years. One treatment consists of conventional medical management including aspirin, beta blockers, angiotensin converting enzyme (ACE) inhibitors, and risk factor modification. The other treatment consists of conventional medical therapy plus percutaneous coronary intervention and coronary stenting. Clinical outcomes will be compared using an intention-to-treat analysis. The primary composite endpoint is mortality, recurrent myocardial infarction, and hospitalization for NYHA Class IV congestive heart failure over a three year follow-up. Individual components of the study composite primary endpoint will be compared in the two treatment arms, as will the medical costs of the two treatments and the health-related quality of life. The cost-effectiveness of percutaneous revascularization will be assessed in the study population.

Official Title
-----------------
Occluded Artery Trial (OAT) - Randomized Comparative Effectiveness Trial of PCI and Medical Therapy Only Post MI

Conditions
-----------------
Cardiovascular Diseases, Heart Diseases, Myocardial Infarction, Heart Failure, Congestive, Heart Failure

Intervention / Treatment
-----------------
* Drug: Beta adrenergic blockers
* Drug: Platelet inhibitors
* Procedure: PTCA and stents
* Drug: ACE Inhibitors


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Recent MI (3-28 days) (Day 1 is the calendar day of the MI system onset) MI is defined based on at least 2 of 3 MI criteria confirmed by: 1) ischemic symptoms ≥30 minutes, 2) cardiac serum marker elevation (creatine kinase (CK) ≥2x upper limit of normal and CK-MB elevated above the upper limit of the laboratory normal) or troponin T, or troponin I elevated at least twice the upper limit of normal, 3) EKG: New Q-waves of ≥0.03 sec and/or 1/3 of QRS complex in ≥2 related EKG leads. If cardiac serum markers are elevated (2), any one of the following EKG findings satisfy inclusion criteria; new ST-T changes (ST elevation or depression), new left bundle-branch block (LBBB), loss of R-wave voltage ≥50% in ≥2 related leads or deep T wave inversions ≥3mm in ≥2 leads. TIMI flow 0 or 1 in infarct related artery (IRA) Meets criteria for high risk: EF <50% or site of occlusion is proximal, in left anterior descending (proximal to the second major diagonal branch); large right coronary artery; or circumflex, if supplying large obtuse marginal, and part of inferior wall (i.e., large dominant or co-dominant vessel). Exclusion Criteria: Age <18 y Clinical indication for revascularization defined as follows: rest or low-threshold angina after MI; severe inducible ischemia on low level exercise or pharmacological stress testing (ST decreased ≥2 mm or inability to complete stage 1 or achieve 3-4 metabolic equivalents without angina, hypotension, or reversible perfusion defects in multiple territories or decreased wall motion thickening in >2 segments on echocardiogram); left main coronary disease (≥50% stenosis); or triple-vessel disease (3 major epicardial coronaries with >70% stenoses) Serious illness such as cancer or pulmonary disease that limits 3-year survival Severe renal disease defined as serum creatinine >3.0 mg/dL that markedly increases risk of radiographic contrast Severe valvular disease History of anaphylaxis to radiographic contrast Infarct artery too small (reference segment diameter <2.5 mm), target segment within or beyond extreme tortuosity (>90° angulation), or otherwise technically a poor candidate for PCI Chronic occlusion of IRA (seen on angiogram obtained before index MI or angiographic evidence of chronicity, e.g., presence of bridging collaterals) NYHA classes III-IV CHF; patients may be treated for acute heart failure complicating MI and rescreened Cardiogenic shock or sustained hypotension: systolic BP <90 mm Hg or cardiac index <2.2 L/min per m^2 LV aneurysm in the same location as index MI and present before index MI Inability to cooperate with the protocol Patient refusal or inability to give informed consent Refusal of patient's physician to allow patient to participate Pregnancy Contraindication to anticoagulation during PCI or to routine antiplatelet therapy after stent implantation Qualifying IRA that has been grafted previously; patients with prior CABG may be enrolled if the IRA was not previously grafted Dilated or hypertrophic cardiomyopathy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Optimal Medical Therapy Only (MED)<br>Conventional medical management, including aspirin, beta blockers, angiotensin converting enzyme (ACE) inhibitors, and risk factor modification | Drug: Beta adrenergic blockers<br>* Participants will receive beta adrenergic blockers.<br>* Other names: beta blockers;Drug: Platelet inhibitors<br>* Participants will receive platelet inhibitors.<br>* Other names: Antiplatelet drugs;Drug: ACE Inhibitors<br>* Participants will receive ACE inhibitors.<br>* Other names: angiotensin-converting-enzyme inhibitor;|
| Experimental: Percutaneous Coronary Intervention (PCI)<br>Conventional medical management, including aspirin, beta blockers, angiotensin converting enzyme (ACE) inhibitors, and risk factor modification, plus percutaneous coronary intervention and coronary stenting | Drug: Beta adrenergic blockers<br>* Participants will receive beta adrenergic blockers.<br>* Other names: beta blockers;Drug: Platelet inhibitors<br>* Participants will receive platelet inhibitors.<br>* Other names: Antiplatelet drugs;Procedure: PTCA and stents<br>* Participants will undergo percutaneous coronary intervention (PTCA) and coronary stenting.<br>* Other names: Stent Placement;Drug: ACE Inhibitors<br>* Participants will receive ACE inhibitors.<br>* Other names: angiotensin-converting-enzyme inhibitor;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients That Had a First Occurrence of the Primary End Point (Composite of Death From Any Cause, Nonfatal MI, or Class IV HF) | Number of Patients with Events (death from any cause, nonfatal reinfarction, and hospitalization for New York Heart Association (NYHA) Class IV congestive heart failure). Events were centrally adjudicated. | Measured over a maximum 9-year follow-up period - 6 year median | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Secondary Outcomes (Safety Events) | Number of Participants with Secondary Outcomes (death from any cause, nonfatal MI, class IV HF, cardiac death, occurrence of selected clinical outcomes including stroke, hospitalization for CHF, sustained ventricular tachycardia/ventricular fibrillation, ICD implantation, or the composite end point). Events were centrally adjudicated. | Measured over a maximum 9-year follow-up period - 6 year median |