Cardiovascular Diseases, Heart Diseases, Myocardial Infarction, Heart Failure, Congestive, Heart Failure
Conditions
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.
Interventions
Participants will receive beta adrenergic blockers.
Participants will receive platelet inhibitors.
PROCEDUREPTCA and stents
Participants will undergo percutaneous coronary intervention (PTCA) and coronary stenting.
DRUGACE Inhibitors
Participants will receive ACE inhibitors.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
NYU Langone Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Measured over a maximum 9-year follow-up period - 6 year median | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Secondary Outcomes (Safety Events) | Measured over a maximum 9-year follow-up period - 6 year median | 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. |
Countries
United States
Participant flow
Recruitment details
The primary analysis of the trial included 2166 patients who had been enrolled through December 2005 with an average follow-up of 2.9 years. An additional 35 patients were enrolled through June 2006 during an extended period of enrollment in the nuclear viability ancillary study. All 2201 patients are included here.
Participants by arm
| Arm | Count |
|---|---|
| Percutaneous Coronary Intervention Group Percutaneous Coronary Intervention with stent placement and optimal medical therapy | 1,101 |
| Medical Therapy Group Conventional medical management, including aspirin, beta blockers, angiotensin converting enzyme (ACE) inhibitors, and risk factor modification, plus percutaneous coronary intervention and coronary stenting | 1,100 |
| Total | 2,201 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 102 | 91 |
Baseline characteristics
| Characteristic | Total | Medical Therapy Group | Percutaneous Coronary Intervention Group |
|---|---|---|---|
| Age, Continuous | 58.7 Years STANDARD_DEVIATION 10.9 | 58.7 Years STANDARD_DEVIATION 11.1 | 58.6 Years STANDARD_DEVIATION 10.9 |
| Current cigarette smoker Current Cigaratte Smoker | 859 participants | 431 participants | 428 participants |
| Current cigarette smoker Non-Smoker | 1324 participants | 660 participants | 664 participants |
| Current cigarette smoker Unknown | 18 participants | 9 participants | 9 participants |
| Infarct-related artery Left anterior descending coronary artery | 793 participants | 410 participants | 383 participants |
| Infarct-related artery Left circumflex coronary artery | 335 participants | 158 participants | 177 participants |
| Infarct-related artery Right coronary artery | 1073 participants | 532 participants | 541 participants |
| Interval between MI and randomization | 8 days | 8 days | 8 days |
| Prior History of Characteristics and Risk Factors Angina | 495 participants | 255 participants | 240 participants |
| Prior History of Characteristics and Risk Factors CABG | 9 participants | 4 participants | 5 participants |
| Prior History of Characteristics and Risk Factors Cerebrovascular disease | 82 participants | 34 participants | 48 participants |
| Prior History of Characteristics and Risk Factors Diabetes | 454 participants | 251 participants | 203 participants |
| Prior History of Characteristics and Risk Factors Diabetes - Insulin Use | 124 participants | 61 participants | 63 participants |
| Prior History of Characteristics and Risk Factors Heart Failure | 52 participants | 25 participants | 27 participants |
| Prior History of Characteristics and Risk Factors Hypertension | 1071 participants | 543 participants | 528 participants |
| Prior History of Characteristics and Risk Factors Myocardial infarction | 247 participants | 118 participants | 129 participants |
| Prior History of Characteristics and Risk Factors PCI | 105 participants | 54 participants | 51 participants |
| Prior History of Characteristics and Risk Factors Peripheral-vessel disease | 83 participants | 39 participants | 44 participants |
| Race/Ethnicity, Customized Black or African American | 69 participants | 36 participants | 33 participants |
| Race/Ethnicity, Customized Hispanic | 277 participants | 136 participants | 141 participants |
| Race/Ethnicity, Customized Other | 92 participants | 53 participants | 39 participants |
| Race/Ethnicity, Customized White | 1763 participants | 875 participants | 888 participants |
| Sex: Female, Male Female | 484 Participants | 242 Participants | 242 Participants |
| Sex: Female, Male Male | 1717 Participants | 858 Participants | 859 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 75 / 1,101 | 61 / 1,100 |
| serious Total, serious adverse events | 226 / 1,101 | 227 / 1,100 |
Outcome results
Primary
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.
Time frame: Measured over a maximum 9-year follow-up period - 6 year median
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Percutaneous Coronary Intervention Group | 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) | 230 participants |
| Medical Therapy Group | 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) | 219 participants |
Secondary
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.
Time frame: Measured over a maximum 9-year follow-up period - 6 year median
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Percutaneous Coronary Intervention Group | Number of Participants With Secondary Outcomes (Safety Events) | Fatal and nonfatal reinfarction | 77 participants |
| Percutaneous Coronary Intervention Group | Number of Participants With Secondary Outcomes (Safety Events) | Death or nonfatal reinfarction | 212 participants |
| Percutaneous Coronary Intervention Group | Number of Participants With Secondary Outcomes (Safety Events) | NYHA class IV heart failure (HF) | 51 participants |
| Percutaneous Coronary Intervention Group | Number of Participants With Secondary Outcomes (Safety Events) | NYHA class III or IV HF | 76 participants |
| Percutaneous Coronary Intervention Group | Number of Participants With Secondary Outcomes (Safety Events) | Nonfatal reinfarction | 75 participants |
| Percutaneous Coronary Intervention Group | Number of Participants With Secondary Outcomes (Safety Events) | Death, reinfarction, or NYHA class III or IV HF | 249 participants |
| Percutaneous Coronary Intervention Group | Number of Participants With Secondary Outcomes (Safety Events) | Cardiovascular death | 77 participants |
| Percutaneous Coronary Intervention Group | Number of Participants With Secondary Outcomes (Safety Events) | Stroke | 29 participants |
| Percutaneous Coronary Intervention Group | Number of Participants With Secondary Outcomes (Safety Events) | Death from all causes | 150 participants |
| Medical Therapy Group | Number of Participants With Secondary Outcomes (Safety Events) | Stroke | 24 participants |
| Medical Therapy Group | Number of Participants With Secondary Outcomes (Safety Events) | Death from all causes | 153 participants |
| Medical Therapy Group | Number of Participants With Secondary Outcomes (Safety Events) | Fatal and nonfatal reinfarction | 65 participants |
| Medical Therapy Group | Number of Participants With Secondary Outcomes (Safety Events) | Nonfatal reinfarction | 61 participants |
| Medical Therapy Group | Number of Participants With Secondary Outcomes (Safety Events) | NYHA class IV heart failure (HF) | 53 participants |
| Medical Therapy Group | Number of Participants With Secondary Outcomes (Safety Events) | Cardiovascular death | 81 participants |
| Medical Therapy Group | Number of Participants With Secondary Outcomes (Safety Events) | Death or nonfatal reinfarction | 199 participants |
| Medical Therapy Group | Number of Participants With Secondary Outcomes (Safety Events) | NYHA class III or IV HF | 74 participants |
| Medical Therapy Group | Number of Participants With Secondary Outcomes (Safety Events) | Death, reinfarction, or NYHA class III or IV HF | 235 participants |