Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease

Phase 3

Completed

Conditions: Heart Failure, Congestive
Cardiovascular Diseases
Coronary Disease
Heart Diseases

Interventions: Drug: Active Medication Alone
Procedure: CABG surgery plus MED
Procedure: CABG plus MED and SVR

Registration Number: NCT00023595

Lead Sponsor: Duke University

Brief Summary: This study will compare medical therapy with coronary bypass surgery and/or surgical ventricular reconstruction for patients with congestive heart failure and coronary artery disease (CAD).

Detailed Description: BACKGROUND:

Congestive heart failure afflicts approximately five million Americans and is the leading cause of hospitalization in Americans over the age of 65. Most cases of congestive heart failure are due to CAD. Surprisingly little is known about the relative benefits of medical versus surgical therapy for patients with obstructive coronary disease and congestive heart failure. Randomized studies of medical therapy versus bypass surgery for obstructive coronary disease were conducted in the 1970s and did not include the systematic use of aspirin, arterial conduits, or lipid-lowering medications. In addition, patients with ejection fractions below 35% were specifically excluded from the three large randomized studies of medical therapy versus bypass surgery. While observational data from the 1970s and early 1980s suggest a survival advantage associated with bypass surgery in patients with low ejection fraction and congestive heart failure, biases favoring the referral of the fittest of such patients for bypass surgery may have confounded these comparisons. In addition, medical therapy for congestive heart failure has improved dramatically over the past two decades. Thus, the choice of medical therapy versus bypass surgery for patients with congestive heart failure and obstructive coronary disease is usually decided by guesswork. This study is designed to provide a solid answer.

PURPOSE:

STICH is a multicenter, international, randomized trial that addresses two specific primary hypotheses in patients with clinical heart failure (HF) and left ventricular (LV) dysfunction who have coronary artery disease amenable to surgical revascularization.

The first hypothesis is that restoration of blood flow by means of coronary revascularization recovers chronic LV dysfunction and improves survival, as compared to intensive medical therapy alone. The second hypothesis is that surgical ventricular restoration (SVR) to a more normal LV size improves survival free of subsequent hospitalization for cardiac cause compared to CABG alone.

Patients eligible for either medical therapy or CABG, but not eligible for the SVR procedure (Stratum A), will be randomized in equal proportions to medical therapy alone versus CABG plus medical therapy. Patients eligible for all three therapies (Stratum B) will be randomized in equal proportions to medical therapy alone, CABG plus medical therapy, and CABG plus SVR plus medical therapy. Patients whose severity of angina or CAD makes them inappropriate for medical therapy alone (Stratum C) will be randomized in equal proportions to CABG plus medical therapy versus CABG plus SVR plus medical therapy.

The overall target was to recruit 1200 patients into Hypothesis One and 1,000 patients into Hypothesis Two. Secondary endpoints include the role of myocardial viability, morbidity, economics, and quality of life. Core laboratories for quality of life/economics, cardiac magnetic resonance (CMR), echocardiography (ECHO), neurohormonal/cytokine/genetic (NCG), and radionuclide (RN) studies ensure consistent testing practices and standardization of data necessary to identify eligible patients and to address specific questions related to the stated hypotheses.

IMPORTANCE OF RESEARCH:

The most common cause of HF is no longer hypertension or valvular heart disease as it was in previous decades, but rather CAD. HF is a common worldwide disease and CAD is a frequent cause of HF initiation and progression. HF is responsible for approximately 1 million hospitalizations and 300,000 fatalities annually. The prevalence of HF is increasing, largely due to enhanced survival following acute myocardial infarction and other manifestations of CAD. No randomized trial has ever compared directly the long-term benefits of surgical, medical, or combined surgical and medical treatment of patients with ischemic HF. The STICH trial is the first trial to compare the long term benefits of surgical and medical treatment in patients with ischemic HF. Although modern medical therapy for HF modestly improves quality of life, a more aggressive approach with the surgical therapies being studied in the STICH trial may produce even greater improvements. The common clinical practice of not offering CABG to patients with LV dysfunction in regions found to be nonviable on noninvasive studies is not evidence-based. Since only those patients for whom intensive medical therapy is the only reasonable therapeutic alternative are excluded from this study, the results of the STICH trial should be applicable to most patients with CAD, HF, and systolic LV dysfunction. The results of the STICH trial will also establish whether measurements of neurohormonal and cytokine levels and genetic profiling are useful for directing patient management decisions, for monitoring the effectiveness of therapy, and for refining the optimal approach for selecting the treatment strategy most likely to be effective for the many of these patients.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 2136

Inclusion Criteria

LV less than 35%, as defined by echocardiogram, left ventriculogram, CMR, or gated single photon emission computed tomography (SPECT) studies
Coronary anatomy suitable for revascularization

Exclusion Criteria

Failure to provide informed consent.
Aortic valvular heart disease clearly indicating the need for aortic valve repair or replacement.
Cardiogenic shock (within 72 hours of randomization), as defined by the need for intraaortic balloon support or the requirement for intravenous inotropic support.
Plan for percutaneous intervention of CAD.
Recent acute MI judged to be an important cause of left ventricular dysfunction.
History of more than 1 prior coronary bypass operation.
Noncardiac illness with a life expectancy of less than 3 years.
Noncardiac illness imposing substantial operative mortality.
Conditions/circumstances likely to lead to poor treatment adherence (eg, history of poor compliance, alcohol or drug dependency, psychiatric illness, no fixed abode).
Previous heart, kidney, liver, or lung transplantation.
Current participation in another clinical trial in which a patient is taking an investigational drug or receiving an investigational medical device.

MED Therapy Eligibility Criteria

Absence of left main CAD as defined by an intraluminal stenosis of 50% or greater.
Absence of CCS III angina or greater (angina markedly limiting ordinary activity).

SVR Eligibility Criterion

• Dominant akinesia or dyskinesia of the anterior left ventricular wall amenable to SVR.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
H01: Medication	Active Medication Alone	Medical therapy alone to treat Coronary Artery Disease
H01: Medication + CABG	CABG surgery plus MED	Coronary artery bypass graft surgery (CABG) plus Medication to treat coronary artery disease
H02: Medication+CABG+SVR	CABG plus MED and SVR	CABG plus Medication and Surgical ventricular reconstruction (SVR)
H02: Medication+CABG	CABG surgery plus MED	Coronary artery bypass graft surgery (CABG) plus Medication to treat coronary artery disease

Primary Outcome Measures

Name	Time	Method
H02: All-cause Mortality or Cardiovascular Hospitalization	5 years post randomization
H01: All Cause Mortality	10 years post randomization

Secondary Outcome Measures

Name	Time	Method
H02: All-cause Mortality	up to 5 years
H02: All-cause Mortality Within 30 Days After Randomization	30 days post randomization
H01: All-cause Mortality or Revascularization (CABG or PCI)	10 years post randomization	CABG = coronary artery bypass grafting. For patients randomized to CABG or CABG +SVR group, this represents the repeat CABG received during follow-up. PCI = Percutaneous Coronary Intervention.
H02: LVEF by ECHO Core Lab During Follow-up	From randomization to 24 months follow-up	Left ventricular ejection fraction (LVEF) measured by Echocardiography (ECHO) core lab
H01: Mortality or Cardiovascular Hospitalization	up to 10 years post randomization
H01: All-cause Mortality or Heart-failure Hospitalization	10 years post randomization
H01: Heart Failure Hospitalization	10 years post randomization
H01: All-cause Mortality, Heart Transplant or LVAD	10 years post randomization	LVAD=Left Ventricular Assist Device
H01: 6 Minute Walk Distance	From randomization to 24 month follow-up
H02: Heart Failure Hospitalization	5 years post randomization
H01: Stroke	10 years post randomization
H02: Cost of Care	index hospital admission	Hospital costs and physician fees for US patients
H01: Cardiovascular Mortality (Defined as Sudden Death or Death Attributed to Recurrent MI, HF, a Cardiovascular Procedure, Stroke, or Other Cardiovascular Etiology).	5 years post randomization
H01: All-cause Mortality Within 30 Days After Randomization	30 days post randomization
H01: Cardiac Procedure: Heart Transplant	10 years post randomization
H01: Cardiac Procedure: Left Ventricular Assist Device (LVAD)	10 years post randomization
H02: Cardiac Procedure: Left Ventricular Assist Device (LVAD)	5 years post randomization
H01: Cardiac Procedure: Implantable Cardioverter Defibrillator (ICD)	10 years post randomization
H02: Cardiac Procedure: Implantable Cardioverter Defibrillator (ICD)	5 years post randomization
H02: All-cause Mortality or Heart-failure Hospitalization	5 years post randomization
H02: Cardiac Procedure: Heart Transplant	5 years post randomization
H02: All-cause Mortality or Revascularization (CABG or PCI)	5 years post randomization	CABG = coronary artery bypass grafting. For patients randomized to CABG or CABG +SVR group, this represents the repeat CABG received during follow-up. PCI = Percutaneous Coronary Intervention.
H01: All-cause (Unplanned and Elective) Hospitalization	10 years post randomization
H02: SF-36 Role Emotional Subscale	From enrollment to 3-year follow-up	These 3 items assess limitations and difficulty performing work or other usual activities as a result of any emotional problems (such as feeling depressed or anxious). Response choices are either "Yes" (1) or "No" (2). Item values are summed and then transformed to a 0-100 scale where higher scores indicate better outcomes. (Final scores are normalized to a mean of 50 and standard deviation of 10.)
H01:SF-36 Social Functioning Subscale	From enrollment to 3-year follow-up	These 2 items assess the limitations on social activities with others. Response choices range from "Extremely" or "All of the time" (1) to "Not at all" or "None of the time" (5). Item values are summed and then transformed to a 0-100 scale where higher scores indicate better social functioning. (Final scores are normalized to a mean of 50 and standard deviation of 10.)
H02: Stroke	5 years post randomization
H02: All-cause Mortality, Heart Transplant or LVAD	5 years post randomization
H02: All-cause (Unplanned and Elective) Hospitalization	5 years post randomization
H02: 6 Minute Walk Distance	From randomization to 24 month follow-up
H01: Exercise Duration	From randomization to 24 months follow-up	Record the total duration of exercise in minutes and seconds for patients performing the modified Bruce exercise treadmill test
H02: B-type Natriuretic Peptide (BNP)	From randomization to 24 months follow-up	B-type natriuretic peptide (BNP) by Neurohormonal/cytokine/genetic (NCG) core lab during follow-up
H01: SF-36 Mental Health Subscale	From enrollment to 3-year follow-up	Short Form 36 Health Status Questionnaire (SF-36) Mental Health Subscale: These 5 items assess anxiety, depression, emotional control, and psychological well-being. Response choices range from "All of the time" (1) to "None of the time" (6). Item values are summed and then transformed to a 0-100 scale where higher scores indicate better mental health. (Final scores are normalized to a mean of 50 and standard deviation of 10.)
H02: SF-36 Social Functioning Subscale	From enrollment to 3-year follow-up	These 2 items assess the limitations on social activities with others. Response choices range from "Extremely" or "All of the time" (1) to "Not at all" or "None of the time" (5). Item values are summed and then transformed to a 0-100 scale where higher scores indicate better social functioning. (Final scores are normalized to a mean of 50 and standard deviation of 10.)
H02: SF-12 Mental Component Summary (MCS) Scale	From enrollment to 3-year follow-up	Twelve items that reflect both physical and mental health are selected from the SF-36 subscales and combined according to an algebraic formula using published weights and constants: (a) First, the items are coded so that a higher value indicates better health; (b) then indicator variables (1/0) are created for the item response choice categories; (c) next, the 35 indicator variables are weighted using "mental" regression weights from the general US population and summed to produce the MCS-12 score; and (d) finally, a normalized score (with a mean of 50 and standard deviation of 10) is obtained by adding the "mental" constant from the scoring table to the sum of the 35 products.
H02: KCCQ Symptom Frequency	From enrollment to 3-year follow-up	These 4 items assess how many times the patient has been bothered by shortness of breath, fatigue, and ankle swelling over the past 2 weeks. Response choices vary, but they range from "Every morning" or "Every night" or "All of the time" (1) to "Never over the past 2 weeks" (either 5 or 7). Mean scores are transformed to a 0-100 scale with high scores representing better outcomes.
H01: LVEF by ECHO Core Lab During Follow-up	From randomization to 24 months follow-up	Left ventricular ejection fraction (LVEF) measured by Echocardiography (ECHO) core lab
H01: LVEF by RN Core Lab During Follow-up	From randomization to 24 months follow-up	Left ventricular ejection fraction (LVEF) measured by radionuclide (RN) core lab.
H02: SF-36 Role Physical Subscale	From enrollment to 3-year follow-up	These 4 items assess limitations and difficulty performing work or other usual activities as a result of one's physical health. Response choices are either "Yes" (1) or "No" (2). Item values are summed and then transformed to a 0-100 scale where higher scores indicate better outcomes. (Final scores are normalized to a mean of 50 and standard deviation of 10.)
H01:SF-36 Role Emotional Subscale	From enrollment to 3-year follow-up	These 3 items assess limitations and difficulty performing work or other usual activities as a result of any emotional problems (such as feeling depressed or anxious). Response choices are either "Yes" (1) or "No" (2). Item values are summed and then transformed to a 0-100 scale where higher scores indicate better outcomes. (Final scores are normalized to a mean of 50 and standard deviation of 10.)
H02: SF-36 Vitality Subscale	From enrollment to 3-year follow-up	These 4 items assess energy level and fatigue. Response choices range from "All of the time" (1) to "None of the time" (6). Item values are summed and then transformed to a 0-100 scale where higher scores indicate better vitality. (Final scores are normalized to a mean of 50 and standard deviation of 10.)
H02: Exercise Duration	From randomization to 24 months follow-up	Record the total duration of exercise in minutes and seconds for patients performing the modified Bruce exercise treadmill test
H02: LVEF by RN Core Lab During Follow-up	From randomization to 24 months follow-up	Left ventricular ejection fraction (LVEF) measured by radionuclide (RN) core lab.
H02: SF-36 Mental Health Subscale	From enrollment to 3-year follow-up	These 5 items assess anxiety, depression, emotional control, and psychological well-being. Response choices range from "All of the time" (1) to "None of the time" (6). Item values are summed and then transformed to a 0-100 scale where higher scores indicate better mental health. (Final scores are normalized to a mean of 50 and standard deviation of 10.)
H01:SF-36 Role Physical Subscale	From enrollment to 3-year follow-up	These 4 items assess limitations and difficulty performing work or other usual activities as a result of one's physical health. Response choices are either "Yes" (1) or "No" (2). Item values are summed and then transformed to a 0-100 scale where higher scores indicate better outcomes. (Final scores are normalized to a mean of 50 and standard deviation of 10.)
H01: KCCQ Physical Limitation Scale	From enrollment to 3-year follow-up	Kansas City Cardiomyopathy Questionnaire (KCCQ)Physical Limitation Scale: These 6 items assess ability to perform various activities of daily living. Response choices range from "Extremely limited" (1) to "Not at all limited" (5). Mean scores are transformed to a 0-100 scale with high scores representing better outcomes. .
H01: KCCQ Symptom Stability	From enrollment to 3-year follow-up	This item assesses changes in shortness of breath or fatigue over the past 2 weeks. Response choices range from "Much worse" (1) to "Much better" (5). Item score is transformed to a 0-100 scale with a high score representing a better outcome. .
H01: LVEF by CMR Core Lab During Follow-up	From randomization to 24 months follow-up	Left ventricular ejection fraction (LVEF) measured by cardiovascular magnetic resonance (CMR) core lab.
H02: LVEF by CMR Core Lab During Follow-up	From randomization to 24 months follow-up	Left ventricular ejection fraction (LVEF) measured by cardiovascular magnetic resonance (CMR) core lab.
H01: B-type Natriuretic Peptide (BNP)	From randomization to 24 months follow-up	B-type natriuretic peptide (BNP) by Neurohormonal/cytokine/genetic (NCG) core lab during follow-up
H01:SF-36 Vitality Subscale	From enrollment to 3-year follow-up	These 4 items assess energy level and fatigue. Response choices range from "All of the time" (1) to "None of the time" (6). Item values are summed and then transformed to a 0-100 scale where higher scores indicate better vitality. (Final scores are normalized to a mean of 50 and standard deviation of 10.)
H01: SF-12 Mental Component Summary (MCS) Scale	From enrollment to 3-year follow-up	Twelve items that reflect both physical and mental health are selected from the SF-36 subscales and combined according to an algebraic formula using published weights and constants: (a) First, the items are coded so that a higher value indicates better health; (b) then indicator variables (1/0) are created for the item response choice categories; (c) next, the 35 indicator variables are weighted using "mental" regression weights from the general US population and summed to produce the MCS-12 score; and (d) finally, a normalized score (with a mean of 50 and standard deviation of 10) is obtained by adding the "mental" constant from the scoring table to the sum of the 35 products.
H01: KCCQ Symptom Burden	From enrollment to 3-year follow-up	These 3 items assess how much the patient has been bothered by shortness of breath, fatigue, and ankle swelling over the past 2 weeks. Response choices range from "extremely bothersome" (1) to "Not at all bothersome" (5). Mean scores are transformed to a 0-100 scale with high scores representing better outcomes.
H02: KCCQ Total Symptoms	From enrollment to 3-year follow-up	This score represents the mean of the Symptom Frequency and Symptom Burden scores. Mean scores are transformed to a 0-100 scale with high scores representing better outcomes.
H01: KCCQ Overall Summary Score	From enrollment to 3-year follow-up	This score represents the mean of these 4 scores: Physical Limitation, Total Symptom, Quality of Life, and Social Limitation. Mean scores are transformed to a 0-100 scale with high scores representing better outcomes. .
H01:Seattle Angina Questionnaire (SAQ) Quality-of-Life Subscale	From enrollment to 3-year follow-up	These 3 items measure the patient's general satisfaction with life. Response choices range from 1 (least enjoyment) to 5 (high satisfaction). The mean score is transformed to a 0-100 scale where higher scores reflect better outcomes. .
H01:SF-12 Physical Component Summary (PCS) Scale	From enrollment to 3-year follow-up	Twelve items that reflect both physical and mental health are selected from the SF-36 subscales and combined according to an algebraic formula using published weights and constants: (a) First, the items are coded so that a higher value indicates better health; (b) then indicator variables (1/0) are created for the item response choice categories; (c) next, the 35 indicator variables are weighted using "physical" regression weights from the general US population and summed to produce the PCS-12 score; and (d) finally, a normalized score (with a mean of 50 and standard deviation of 10) is obtained by adding the "physical" constant from the scoring table to the sum of the 35 products.
H02: SF-12 Physical Component Summary (PCS) Scale	From enrollment to 3-year follow-up	Twelve items that reflect both physical and mental health are selected from the SF-36 subscales and combined according to an algebraic formula using published weights and constants: (a) First, the items are coded so that a higher value indicates better health; (b) then indicator variables (1/0) are created for the item response choice categories; (c) next, the 35 indicator variables are weighted using "physical" regression weights from the general US population and summed to produce the PCS-12 score; and (d) finally, a normalized score (with a mean of 50 and standard deviation of 10) is obtained by adding the "physical" constant from the scoring table to the sum of the 35 products.
H02: KCCQ Physical Limitation Scale	From enrollment to 3-year follow-up	These 6 items assess ability to perform various activities of daily living. Response choices range from "Extremely limited" (1) to "Not at all limited" (5). Mean scores are transformed to a 0-100 scale with high scores representing better outcomes.
H02: KCCQ Symptom Stability	From enrollment to 3-year follow-up	This item assesses changes in shortness of breath or fatigue over the past 2 weeks. Response choices range from "Much worse" (1) to "Much better" (5). Item score is transformed to a 0-100 scale with a high score representing a better outcome.
H01: KCCQ Symptom Frequency	From enrollment to 3-year follow-up	These 4 items assess how many times the patient has been bothered by shortness of breath, fatigue, and ankle swelling over the past 2 weeks. Response choices vary, but they range from "Every morning" or "Every night" or "All of the time" (1) to "Never over the past 2 weeks" (either 5 or 7). Mean scores are transformed to a 0-100 scale with high scores representing better outcomes. .
H01: KCCQ Total Symptoms	From enrollment to 3-year follow-up	This score represents the mean of the Symptom Frequency and Symptom Burden scores. Mean scores are transformed to a 0-100 scale with high scores representing better outcomes. .
H01: KCCQ Quality-of-Life Scale	From enrollment to 3-year follow-up	These 3 items assess the effect of heart failure on the patient's enjoyment of life. Response choices range from 1 (worst state) to 5 (best state). Mean scores are transformed to a 0-100 scale with high scores representing better outcomes. .
H01: KCCQ Clinical Summary Score	From enrollment to 3-year follow-up	This score represents the mean of the Physical Limitation and Total Symptom scores. Mean scores are transformed to a 0-100 scale with high scores representing better outcomes. .
H02: KCCQ Clinical Summary Score	From enrollment to 3-year follow-up	This score represents the mean of the Physical Limitation and Total Symptom scores. Mean scores are transformed to a 0-100 scale with high scores representing better outcomes.
H02: KCCQ Overall Summary Score	From enrollment to 3-year follow-up	This score represents the mean of these 4 scores: Physical Limitation, Total Symptom, Quality of Life, and Social Limitation. Mean scores are transformed to a 0-100 scale with high scores representing better outcomes.
H02: KCCQ Quality-of-Life Scale	From enrollment to 3-year follow-up	These 3 items assess the effect of heart failure on the patient's enjoyment of life. Response choices range from 1 (worst state) to 5 (best state). Mean scores are transformed to a 0-100 scale with high scores representing better outcomes.
H01: KCCQ Social Limitation	From enrollment to 3-year follow-up	These 4 items assess how much heart failure has affected the patient's lifestyle. Response choices range from "Severely limited" (1) to "Did not limit at all" (5). Mean scores are transformed to a 0-100 scale with high scores representing better outcomes. .
H02: KCCQ Social Limitation	From enrollment to 3-year follow-up	These 4 items assess how much heart failure has affected the patient's lifestyle. Response choices range from "Severely limited" (1) to "Did not limit at all" (5). Mean scores are transformed to a 0-100 scale with high scores representing better outcomes.
H01: Seattle Angina Questionnaire (SAQ) Anginal Stability Subscale	From enrollment to 3-year follow-up	This item assesses the change in chest pain over the last 4 weeks. Response choices range from "Much more often" (1) to "None" (6). The mean response is transformed to a 0-100 scale where 50 represents no change and a higher score indicates less angina. .
H01: EQ-5D Health Status Index Score	From enrollment to 3-year follow-up	This 5-item scale describes a patient's health in terms of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Choices for each dimension are "No problems" (1), "Moderate problems" (2), or "Extreme problems" (3). A scoring algorithm with utility weights is then applied to these 5 items to generate index scores ranging from -0.11 (i.e., 33333) to 1.0 (i.e., 11111) on a scale where 0.0 = death and 1.0 = perfect health. These scores were multiplied by 100 to produce a scale from -11 to 100 that more closely resembles the Visual Analog Scale. .
H02: Cardiac Self-Efficacy (CSE) Control Symptoms Subscale	From enrollment to 3-year follow-up	These 8 items assess patients' ability to control symptoms such as chest pain and breathlessness by taking their medications and adjusting their activity levels. Response choices range from "Not at all confident" (1) to "Completely confident" (5). The mean score is transformed to a 0-100 scale where higher scores reflect more confidence.
H01: General Health Rating Scale	From enrollment to 3-year follow-up	This single item asks patients to describe their health status over the past month on a scale from 0 to 100, where 0 = death and 100 = excellent health. .
H02: KCCQ Symptom Burden	From enrollment to 3-year follow-up	These 3 items assess how much the patient has been bothered by shortness of breath, fatigue, and ankle swelling over the past 2 weeks. Response choices range from "extremely bothersome" (1) to "Not at all bothersome" (5). Mean scores are transformed to a 0-100 scale with high scores representing better outcomes.
H02: Seattle Angina Questionnaire (SAQ) Anginal Frequency Subscale	From enrollment to 3-year follow-up	These 2 items assess the frequency of chest pain over the last 4 weeks. Response choices range from "4 or more times a day" (1) to "None" (6). The mean response is transformed to a 0-100 scale where higher scores reflect less frequent angina.
H02: Percentage of Patients With a Score of >= 16 on the Center for Epidemiological Studies Depression (CES-D) Scale	From enrollment to 3-year follow-up	These 20 items assess depressive symptomatology, and responses choices range from "Rarely or none of the time" (0) to "Most or all of the time" (3). Scale scores can therefore range from 0 to 60, although scores greater than or equal to 16 are considered high.
H01: Cardiac Self-Efficacy (CSE) Control Symptoms Subscale	From enrollment to 3-year follow-up	These 8 items assess patients' ability to control symptoms such as chest pain and breathlessness by taking their medications and adjusting their activity levels. Response choices range from "Not at all confident" (1) to "Completely confident" (5). The mean score is transformed to a 0-100 scale where higher scores reflect more confidence. .
H01: Seattle Angina Questionnaire (SAQ) Anginal Frequency Subscale	From enrollment to 3-year follow-up	These 2 items assess the frequency of chest pain over the last 4 weeks. Response choices range from "4 or more times a day" (1) to "None" (6). The mean response is transformed to a 0-100 scale where higher scores reflect less frequent angina. .
H02: Seattle Angina Questionnaire (SAQ) Anginal Stability Subscale	From enrollment to 3-year follow-up	This item assesses the change in chest pain over the last 4 weeks. Response choices range from "Much more often" (1) to "None" (6). The mean response is transformed to a 0-100 scale where 50 represents no change and a higher score indicates less angina.
H01: EQ-5D Visual Analog Scale	From enrollment to 3-year follow-up	Euro QoL 5 Dimensions Quality of Life Instrument (EQ-5D): This 0-100 scale records the patient's self-rated health on a vertical scale where 0 = worst imaginable health and 100 = perfect health. .
H01: Cardiac Self-Efficacy (CSE) Maintain Functioning Subscale	From enrollment to 3-year follow-up	These 5 items assess patients' ability to maintain their usual social, family, and physical activities. Response choices range from "Not at all confident" (1) to "Completely confident" (5). The mean score is transformed to a 0-100 scale where higher scores reflect more confidence. .
H02: General Health Rating Scale	From enrollment to 3-year follow-up	This single item asks patients to describe their health status over the past month on a scale from 0 to 100, where 0 = death and 100 = excellent health.
H01: Cost of Care	index hospital admission	Hospital costs and physician fees for US patients
H02: Seattle Angina Questionnaire (SAQ) Quality-of-Life Subscale	From enrollment to 3-year follow-up	These 3 items measure the patient's general satisfaction with life. Response choices range from 1 (least enjoyment) to 5 (high satisfaction). The mean score is transformed to a 0-100 scale where higher scores reflect better outcomes.
H02: EQ-5D Visual Analog Scale	From enrollment to 3-year follow-up	This 0-100 scale records the patient's self-rated health on a vertical scale where 0 = worst imaginable health and 100 = perfect health.
H02: EQ-5D Health Status Index Score	From enrollment to 3-year follow-up	This 5-item scale describes a patient's health in terms of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Choices for each dimension are "No problems" (1), "Moderate problems" (2), or "Extreme problems" (3). A scoring algorithm with utility weights is then applied to these 5 items to generate index scores ranging from -0.11 (i.e., 33333) to 1.0 (i.e., 11111) on a scale where 0.0 = death and 1.0 = perfect health. (These scores can be multiplied by 100 to produce a scale from -11 to 100 that more closely resembles the Visual Analog Scale.)
H01: Percentage of Patients With a Score of >= 16 on the Center for Epidemiological Studies Depression (CES-D) Scale	From enrollment to 3-year follow-up	These 20 items assess depressive symptomatology, and responses choices range from "Rarely or none of the time" (0) to "Most or all of the time" (3). Scale scores can therefore range from 0 to 60, although scores greater than or equal to 16 are considered high. .
H02: Cardiac Self-Efficacy (CSE) Maintain Functioning Subscale	From enrollment to 3-year follow-up	These 5 items assess patients' ability to maintain their usual social, family, and physical activities. Response choices range from "Not at all confident" (1) to "Completely confident" (5). The mean score is transformed to a 0-100 scale where higher scores reflect more confidence.