Comparison of Characteristics and Outcomes of Veterans With Stable Ischemic Heart Disease Enrolled in the COURAGE Trial Versus the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program.

Randomized clinical trials have not demonstrated a survival benefit with percutaneous coronary intervention in stable ischemic heart disease (SIHD). We evaluated the generalizability of the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial findings to the broader population of veterans with SIHD. Veterans who underwent coronary angiography between 2005 and 2013 for SIHD were identified from the Veterans Affairs Clinical Assessment, Reporting and Tracking Program (VA CART). Patient-level comparisons were made between patients from VA CART who met the eligibility criteria for COURAGE and veterans enrolled in COURAGE between 1999 and 2004. All-cause mortality over long-term follow-up was assessed using Cox proportional hazards models. COURAGE-eligible patients from VA CART (n = 59,758) were older, had a higher body mass index, a greater prevalence of co-morbidities, but fewer diseased vessels on index coronary angiography, and were less likely to be on optimal medical therapy at baseline and on 1-year follow-up compared with VA COURAGE participants (n = 968). Patients from VA CART (median follow-up 6.5 years) had higher all-cause mortality (adjusted hazard ratio [aHR] 1.98 [1.61 to 2.43]) than participants from VA COURAGE (median follow-up: 4.6 years). Risks of mortality were greater in the 56.4% patients from CART who were medically managed (aHR 1.94 [1.49 to 2.53]) and in the 43.6% who underwent percutaneous coronary intervention (aHR 1.99 [1.45 to 2.74]), compared with their respective VA COURAGE arms. In conclusion, in this noncontemporaneous patient-level analysis, veterans in the randomized COURAGE trial had more favorable outcomes than the population of veterans with SIHD at large.

Angina Severity, Mortality, and Healthcare Utilization Among Veterans With Stable Angina.

Background Canadian Cardiovascular Society (CCS) angina severity classification is associated with mortality, myocardial infarction, and coronary revascularization in clinical trial and registry data. The objective of this study was to determine associations between CCS class and all-cause mortality and healthcare utilization, using natural language processing to extract CCS classifications from clinical notes. Methods and Results In this retrospective cohort study of veterans in the United States with stable angina from January 1, 2006, to December 31, 2013, natural language processing extracted CCS classifications. Veterans with a prior diagnosis of coronary artery disease were excluded. Outcomes included all-cause mortality (primary), all-cause and cardiovascular-specific hospitalizations, coronary revascularization, and 1-year healthcare costs. Of 299 577 veterans identified, 14 216 (4.7%) had ≥1 CCS classification extracted by natural language processing. The mean age was 66.6±9.8 years, 99% of participants were male, and 81% were white. During a median follow-up of 3.4 years, all-cause mortality rates were 4.58, 4.60, 6.22, and 6.83 per 100 person-years for CCS classes I, II, III, and IV, respectively. Multivariable adjusted hazard ratios for all-cause mortality comparing CCS II, III, and IV with those in class I were 1.05 (95% CI, 0.95-1.15), 1.33 (95% CI, 1.20-1.47), and 1.48 (95% CI, 1.25-1.76), respectively. The multivariable hazard ratio comparing CCS IV with CCS I was 1.20 (95% CI, 1.09-1.33) for all-cause hospitalization, 1.25 (95% CI, 0.96-1.64) for acute coronary syndrome hospitalizations, 1.00 (95% CI, 0.80-1.26) for heart failure hospitalizations, 1.05 (95% CI, 0.88-1.25) for atrial fibrillation hospitalizations, 1.92 (95% CI, 1.40-2.64) for percutaneous coronary intervention, and 2.51 (95% CI, 1.99-3.16) for coronary artery bypass grafting surgery. Conclusions Natural language processing-extracted CCS classification was positively associated with all-cause mortality and healthcare utilization, demonstrating the prognostic importance of anginal symptom assessment and documentation.

Healthy Behavior, Risk Factor Control, and Survival in the COURAGE Trial.

BACKGROUND: Individual risk factor control improves survival in patients with stable ischemic heart disease (SIHD). It is uncertain if multiple risk factor control further extends survival. OBJECTIVES: This study determined whether a greater number of risk factors at goal predicted improved survival in SIHD patients. METHODS: Of 2,287 participants in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial, 2,102 (92%) had complete ascertainment of 6 pre-specified risk factors: systolic blood pressure, low-density lipoprotein cholesterol, smoking, physical activity, diet, and body mass index. Participants received interventions to control these risk factors. The outcome measure was mortality. RESULTS: During a mean follow-up of 6.8 years, 473 (22.5%) subjects died. In univariate analysis, the greater the number of risk factors controlled, the higher the probability of survival (unadjusted log rank: p < 0.001). In multivariate analysis, the strongest predictors at 1 year of improved survival were being a nonsmoker, regular physical activity, having a systolic blood pressure <130 mm Hg, and following the American Heart Association Step 2 diet. Baseline risk factor values and evidence-based medications did not independently predict survival once risk factor control at 1 year was included in the model. Having 4 to 6 risk factors compared with 0 to 1 risk factor at goal predicted lower mortality (hazard ratios for 4 and 6 controlled risk factors: 0.64; 95% confidence interval: 0.41 to 0.98, and 0.27; 95% confidence interval: 0.09 to 0.79, respectively). CONCLUSIONS: The greater the number of risk factors in control, the higher the probability of survival in patients with SIHD. More effective strategies are needed to achieve comprehensive risk factor control, including healthy behaviors. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation [COURAGE]; NCT00007657).

Treatment and outcomes of type 2 myocardial infarction and myocardial injury compared with type 1 myocardial infarction.

BACKGROUND: Type 2 myocardial infarction (MI) is defined by a rise and fall of cardiac biomarkers and evidence of ischemia without unstable coronary artery disease (CAD) because of a mismatch in myocardial oxygen supply and demand. Myocardial injury is similar but does not fulfill the clinical criteria for MI. There is uncertainty in terms of the clinical characteristics, management, and outcomes of type 2 MI and myocardial injury in comparison with type 1 MI. PATIENTS AND METHODS: Patients admitted to a Veterans Affairs tertiary care hospital with a rise and fall in cardiac troponin were identified. MI and injury subtypes, presentation, management, and outcomes were determined. RESULTS: Type 1 MI, type 2 MI, and myocardial injury occurred in 137, 146, and 175 patients, respectively. Patients with type 2 MI were older (P=0.02), had lower peak cardiac troponin (P<0.001), and were less likely to receive aspirin and statin at discharge (P<0.001) than type 1 MI survivors. All-cause mortality (median follow-up: 1.8 years) was not different between patient groups (type 1 MI mortality: 29.9%, type 2 MI: 30.8%, myocardial injury: 29.7%; log rank P=0.94). A significant proportion of deaths were attributed to cardiovascular causes in all subgroups (type 1 MI: 34.1%, type 2 MI: 17.8%, myocardial injury: 30.8%). CONCLUSION: Patients with type 2 MI and myocardial injury were less likely to receive medical therapy for CAD than those with type 1 MI. No differences in all-cause mortality among MI subtypes were observed. Additional studies to determine optimal medical therapy and risk stratification strategies for these high-risk populations are warranted.

Effect of Percutaneous Coronary Intervention on Survival in Patients with Stable Ischemic Heart Disease.

PURPOSE OF REVIEW: This study aims to determine if percutaneous coronary intervention (PCI) does improve survival in stable ischemic heart disease (SIHD). RECENT FINDINGS: The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial will evaluate patients with moderate to severe ischemia and will be the largest randomized trial of an initial management strategy of coronary revascularization (percutaneous or surgical) versus optimal medical therapy alone for SIHD. Although the ISCHEMIA trial may show a benefit with upfront coronary revascularization in this high-risk population, cardiac events after PCI are largely caused by plaque rupture in segments outside of the original stented segment. Furthermore, given the robust data from prior randomized trials, which showed no survival benefit with PCI, and the likelihood that the highest risk patients in ISCHEMIA will be treated with surgery, it is unlikely that the ISCHEMIA trial will show a survival benefit particular to PCI. RECENT FINDINGS: Although PCI relieves symptoms, the evidence base indicates that it does not prolong survival in SIHD.

Association Between Gout and Aortic Stenosis.

BACKGROUND: An independent association between gout and coronary artery disease is well established. The relationship between gout and valvular heart disease, however, is unclear. The aim of this study was to assess the association between gout and aortic stenosis. METHODS: We performed a retrospective case-control study. Aortic stenosis cases were identified through a review of outpatient transthoracic echocardiography (TTE) reports. Age-matched controls were randomly selected from patients who had undergone TTE and did not have aortic stenosis. Charts were reviewed to identify diagnoses of gout and the earliest dates of gout and aortic stenosis diagnosis. RESULTS: Among 1085 patients who underwent TTE, 112 aortic stenosis cases were identified. Cases and nonaortic stenosis controls (n = 224) were similar in age and cardiovascular comorbidities. A history of gout was present in 21.4% (n = 24) of aortic stenosis subjects compared with 12.5% (n = 28) of controls (unadjusted odds ratio 1.90, 95% confidence interval 1.05-3.48, P = .038). Multivariate analysis retained significance only for gout (adjusted odds ratio 2.08, 95% confidence interval 1.00-4.32, P = .049). Among subjects with aortic stenosis and gout, gout diagnosis preceded aortic stenosis diagnosis by 5.8 ± 1.6 years. The age at onset of aortic stenosis was similar among patients with and without gout (78.7 ± 1.8 vs 75.8 ± 1.0 years old, P = .16). CONCLUSIONS: Aortic stenosis patients had a markedly higher prevalence of precedent gout than age-matched controls. Whether gout is a marker of, or a risk factor for, the development of aortic stenosis remains uncertain. Studies investigating the potential role of gout in the pathophysiology of aortic stenosis are warranted and could have therapeutic implications.

Relationship between neutrophil-lymphocyte ratio and severity of lower extremity peripheral artery disease.

BACKGROUND: The aim of this study was to determine the association between neutrophil-lymphocyte ratio (NLR) and severity of lower extremity peripheral artery disease (PAD). METHODS: A retrospective chart review identified 928 patients referred for peripheral angiography. NLR was assessed from routine pre-procedural hemograms with automated differentials and available in 733 patients. Outcomes of interest were extent of disease on peripheral angiography and target vessel revascularization. Median follow-up was 10.4months. Odds ratio (OR) [95% confidence intervals] was assessed using a logistic regression model. RESULTS: There was a significant association between elevated NLR and presence of severe multi-level PAD versus isolated suprapopliteal or isolated infrapopliteal disease (OR 1.11 [1.03-1.19], p=0.007). This association remained significant even after adjustment for age (OR 1.09 [1.01-1.17], p=0.02); age, sex, race, and body mass index (OR 1.08 [1.00-1.16], p=0.046); and age, sex, race, body mass index, hypertension, diabetes mellitus, coronary artery disease, and creatinine (OR 1.07 [1.00-1.15], p=0.049). After additional adjustment for clinical presentation, there was a trend towards association between NLR and severe multi-level PAD (OR 1.07 [1.00-1.15], p=0.056), likely limited by sample size. In patients who underwent endovascular intervention (n=523), there was no significant difference in rate of target vessel revascularization across tertiles of NLR (1st tertile 14.8%, 2nd tertile 14.1%, 3rd tertile 20.1%; p=0.32). CONCLUSION: In a contemporary cohort of patients undergoing peripheral angiography with possible endovascular intervention, elevated NLR was independently associated with severe multi-level PAD. Larger studies evaluating the association between this inexpensive biomarker and clinical outcomes are warranted.

Revascularization Strategies in Patients with Diabetes Mellitus and Acute Coronary Syndrome.

Patients with diabetes mellitus (DM) have more severe CAD and higher mortality in acute coronary syndrome (ACS) than patients without DM. The optimal mode of revascularization-coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI)-remains controversial in this setting. For patients with DM and ST-segment elevation myocardial infarction, prompt revascularization of the culprit artery via PCI is generally preferable. In non-ST-elevation ACS, the decision on mode of revascularization is more challenging. Trials comparing CABG with percutaneous transluminal coronary angioplasty, bare metal stents, and first-generation drug-eluting stents in DM patients with multivessel have demonstrated decreased mortality in those receiving CABG. On the other hand, trials and retrospective analyses comparing CABG to PCI with second-generation drug-eluting stents have not shown a statistically significant mortality benefit favoring CABG. This potentially narrowed that gap between CABG and PCI requires further investigation.

Provoking conditions, management and outcomes of type 2 myocardial infarction and myocardial necrosis.

BACKGROUND: Type 2 myocardial infarction (MI) is defined as myocardial necrosis (myonecrosis) due to an imbalance in supply and demand with clinical evidence of ischemia. Some clinical scenarios of supply-demand mismatch predispose to myonecrosis but limit the identification of symptoms and ECG changes referable to ischemia; therefore, the MI definition may not be met. Factors that predispose to type 2 MI and myonecrosis without definite MI, approaches to treatment, and outcomes remain poorly characterized. METHODS: Patients admitted to an academic medical center with an ICD-9 diagnosis of secondary myocardial ischemia or non-primary diagnosis of non-ST-elevation MI were retrospectively reviewed. Cases were classified as either MI (n=255) or myonecrosis without definite MI (n=220) based on reported symptoms, ischemic ECG changes, and new wall motion abnormalities. RESULTS: Conditions associated with type 2 MI or myonecrosis included non-cardiac surgery (38%), anemia or bleeding requiring transfusion (32%), sepsis (31%), tachyarrhythmia (23%), hypotension (22%), respiratory failure (23%), and severe hypertension (8%). Inpatient mortality was 5%, with no difference between patients with MI and those with myonecrosis (6% vs. 5%, p=0.41). At discharge, only 43% of patients received aspirin and statin therapy. CONCLUSIONS: Type 2 MI and myonecrosis occur frequently in the setting of supply-demand mismatch due to non-cardiac surgery, sepsis, or anemia. Myonecrosis without definite MI is associated with similar in-hospital mortality as type 2 MI; both groups warrant further workup for cardiovascular disease. Antiplatelet and statin prescriptions were infrequent at discharge, reflecting physician uncertainty about the role of secondary prevention in these patients.

Glycemic Control in Coronary Revascularization.

OPINION STATEMENT: Hyperglycemia in the setting of coronary revascularization is associated with increased adverse cardiovascular events in patients with or without diabetes mellitus. Data suggest that acute peri-procedural hyperglycemia causes an increase in inflammation, platelet activity, and endothelial dysfunction and is associated with plaque instability and infarct size. While peri-procedural blood glucose level is an independent predictor of adverse outcomes in patients undergoing coronary revascularization, treatment strategies remain uncertain. Randomized clinical trials of glucose-insulin-potassium infusions have consistently shown no benefit, while those comparing insulin therapy versus standard of care have demonstrated mixed results, likely due to the failure to reach euglycemia with these strategies. Although no glucose-lowering agent has been shown to be superior in peri-procedural glycemic control, the continuation of clinically prescribed long-acting glucose-lowering medications in patients with diabetes mellitus prior to coronary angiography and possible percutaneous coronary intervention may be the simplest and most effective approach to maintain euglycemia and decrease the associated increase in inflammation and platelet activity. However, alternative strategies such as therapies targeted at the underlying mechanism of harm (e.g., more potent anti-platelet therapy, anti-inflammatory therapy) should also be considered and warrant further investigation.

The assessment of thrombotic markers utilizing ionic versus non-ionic contrast during coronary angiography and intervention trial.

OBJECTIVE: To determine how two different types of iodinated contrast media (CM), low-osmolar ionic dimer ioxaglate (Hexabrix) and iso-osmolar non-ionic dimer iodixanol (Visipaque), affect multiple indices of hemostasis. BACKGROUND: In vitro models demonstrate differential effects of ionic and non-ionic CM on markers of hemostasis. METHODS: This blinded endpoint trial randomized 100 patients to ioxaglate or iodixanol. The primary endpoint was change in endogenous thrombin potential (ETP) following diagnostic angiography. Secondary endpoints included change in markers of fibrinolysis [tissue plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1)] and platelet aggregation following diagnostic angiography and percutaneous coronary intervention (PCI) with bivalirudin. Data are presented as median [interquartile range]. RESULTS: ETP significantly decreased after diagnostic angiography in both ioxaglate (baseline 1810 nM*minute [1540-2089] to post-angiography 649 nM*minute [314-1347], p < 0.001) and iodixanol groups (baseline 1682 nM*minute [1534-2147] to post-angiography 681 nM*minute [229-1237], p < 0.001), but the decrease was not different between CM (p = 0.70). There was a significant increase in ETP during PCI (n = 45), despite the use of bivalirudin, suggesting a prothrombotic effect of PCI (post-angiography 764 nM*minute [286-1283] to post-PCI 1081 nM*minute [668-1552], p = 0.02). There were no significant differential effects on tPA, PAI-1, and markers of platelet activity. CONCLUSION: There were no significant differential effects between ioxaglate and iodixanol. Both CM led to significant reductions in thrombin generation and no significant effects on fibrinolytic activity or platelet activity, thereby contributing to a favorable antithrombotic milieu. © 2016 Wiley Periodicals, Inc.

Effect of Colchicine on Platelet-Platelet and Platelet-Leukocyte Interactions: a Pilot Study in Healthy Subjects.

The cardioprotective mechanisms of colchicine in patients with stable ischemic heart disease remain uncertain. We tested varying concentrations of colchicine on platelet activity in vitro and a clinically relevant 1.8-mg oral loading dose administered over 1 h in 10 healthy subjects. Data are shown as median [interquartile range]. Colchicine addition in vitro decreased light transmission platelet aggregation only at supratherapeutic concentrations but decreased monocyte- (MPA) and neutrophil-platelet aggregation (NPA) at therapeutic concentrations. Administration of 1.8 mg colchicine to healthy subjects had no significant effect on light transmission platelet aggregation but decreased the extent of MPA (28 % [22-57] to 22 % [19-31], p = 0.05) and NPA (19 % [16-59] to 15 % [11-30], p = 0.01), platelet surface expression of PAC-1 (370 mean fluorescence intensity (MFI) [328-555] to 333 MFI [232-407], p = 0.02) and P-selectin (351 MFI [269-492] to 279 [226-364], p = 0.03), and platelet adhesion to collagen (10.2 % [2.5-32.6] to 2.0 % [0.2-9.5], p = 0.09) 2 h post-administration. Thus, in clinically relevant concentrations, colchicine decreases expression of surface markers of platelet activity and inhibits leukocyte-platelet aggregation but does not inhibit homotypic platelet aggregation.

Effect of PCI on Long-Term Survival in Patients with Stable Ischemic Heart Disease.

BACKGROUND: Percutaneous coronary intervention (PCI) relieves angina in patients with stable ischemic heart disease, but clinical trials have not shown that it improves survival. Between June 1999 and January 2004, we randomly assigned 2287 patients with stable ischemic heart disease to an initial management strategy of optimal medical therapy alone (medical-therapy group) or optimal medical therapy plus PCI (PCI group) and did not find a significant difference in the rate of survival during a median follow-up of 4.6 years. We now report the rate of survival among the patients who were followed for up to 15 years. METHODS: We obtained permission from the patients at the Department of Veterans Affairs (VA) sites and some non-VA sites in the United States to use their Social Security numbers to track their survival after the original trial period ended. We searched the VA national Corporate Data Warehouse and the National Death Index for survival information and the dates of death from any cause. We calculated survival according to the Kaplan-Meier method and used a Cox proportional-hazards model to adjust for significant between-group differences in baseline characteristics. RESULTS: Extended survival information was available for 1211 patients (53% of the original population). The median duration of follow-up for all patients was 6.2 years (range, 0 to 15); the median duration of follow-up for patients at the sites that permitted survival tracking was 11.9 years (range, 0 to 15). A total of 561 deaths (180 during the follow-up period in the original trial and 381 during the extended follow-up period) occurred: 284 deaths (25%) in the PCI group and 277 (24%) in the medical-therapy group (adjusted hazard ratio, 1.03; 95% confidence interval, 0.83 to 1.21; P=0.76). CONCLUSIONS: During an extended-follow-up of up to 15 years, we did not find a difference in survival between an initial strategy of PCI plus medical therapy and medical therapy alone in patients with stable ischemic heart disease. (Funded by the VA Cooperative Studies Program and others; COURAGE ClinicalTrials.gov number, NCT00007657.).

Effect of baseline exercise capacity on outcomes in patients with stable coronary heart disease (a post hoc analysis of the clinical outcomes utilizing revascularization and aggressive drug evaluation trial).

The impact of baseline exercise capacity on clinical outcomes in patients with stable ischemic heart disease randomized to an initial strategy of optimal medical therapy (OMT) with or without percutaneous coronary intervention (PCI) in the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial has not been studied. A post hoc analysis was performed in 1,052 patients of COURAGE (PCI + OMT: n = 527, OMT: n = 525) who underwent exercise treadmill testing at baseline. Patients were categorized into 2 exercise capacity groups based on metabolic equivalents (METs) achieved during baseline exercise treadmill testing (<7 METs: n = 464, ≥7 METs: n = 588) and were followed for a median of 4.6 years. The primary composite end point of death or myocardial infarction was similar in the PCI + OMT group and the OMT group for patients with exercise capacity <7 METs (19.1% vs 16.1%, p = 0.31) and ≥7 METs (13.3% vs 10.3%, p = 0.27). After adjusting for baseline covariates, the hazard ratio (99% confidence interval) for the primary end point for the PCI + OMT group versus the OMT group was 1.42 (0.90 to 2.23, p = 0.05) and for the exercise capacity subgroups of ≥7 METs and <7 METs was 0.75 (0.46 to 1.22, p = 0.13). There was no statistically significant interaction between the original treatment arm allocation (PCI + OMT vs OMT) and baseline exercise capacity. In conclusion, there was no difference in the long-term clinical outcomes in patients with exercise capacity <7 METs compared with ≥7 METs, irrespective of whether they were assigned to initial PCI. Patients with exercise capacity <7 METs did not derive a proportionately greater clinical benefit from PCI + OMT compared with those patients who received OMT alone.

Diagnostic Accuracy of Cardiac Magnetic Resonance Imaging in the Evaluation of Newly Diagnosed Heart Failure With Reduced Left Ventricular Ejection Fraction.

The aim of this study was to determine the diagnostic value of cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement (LGE), cine imaging, and resting first-pass perfusion (FPP) in the evaluation for ischemic (IC) versus nonischemic (NIC) cardiomyopathy in new-onset heart failure with reduced (≤40%) left ventricular ejection fraction (HFrEF). A retrospective chart review analysis identified 83 patients from January 2009 to June 2012 referred for CMR imaging evaluation for new-onset HFrEF with coronary angiography performed within 6 months of CMR. The diagnosis of IC was established using Felker criteria on coronary angiography. CMR sequences were evaluated for the presence of patterns suggestive of severe underlying coronary artery disease as the cause of HFrEF (subendocardial and/or transmural LGE, regional wall motion abnormality on cine, regional hypoperfusion defect on resting FPP). Discriminative power was assessed using receiver operator characteristics curve analysis. Coronary angiography identified 36 patients (43%) with IC. Presence of subendocardial and/or transmural LGE alone demonstrated good discriminative power (C-statistic 0.85, 95% confidence interval 0.76 to 0.94) for the diagnosis of IC. The presence of an ischemic pattern on both LGE and cine sequences resulted in a specificity of 87% for the diagnosis of IC, whereas the absence of an ischemic pattern on both LGE and cine sequences resulted in a specificity of 94% for the diagnosis of NIC. Addition of resting FPP on a subset of patients did not improve diagnostic values. In conclusion, CMR has potential value in the diagnostic evaluation of IC versus NIC.

Validation of the appropriate use criteria for percutaneous coronary intervention in patients with stable coronary artery disease (from the COURAGE trial).

Establishing the validity of appropriate use criteria (AUC) for percutaneous coronary intervention (PCI) in the setting of stable ischemic heart disease can support their adoption for quality improvement. We conducted a post hoc analysis of 2,287 Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation trial patients with stable ischemic heart disease randomized to PCI with optimal medical therapy (OMT) or OMT alone. Within appropriateness categories, we compared rates of death, myocardial infarction, revascularization subsequent to initial therapy, and angina-specific health status as determined by the Seattle Angina Questionnaire in patients randomized to PCI + OMT to those randomized to OMT alone. A total of 1,987 patients (87.9%) were mapped to the 2012 publication of the AUC, with 1,334 (67.1%) classified as appropriate, 551 (27.7%) uncertain, and 102 (5.1%) as inappropriate. There were no significant differences between PCI and OMT alone in the rate of mortality and myocardial infarction by appropriateness classification. Rates of revascularization were significantly lower in patients initially receiving PCI + OMT who were classified as appropriate (hazard ratio 0.65; 95% confidence interval 0.53 to 0.80; p <0.001) or uncertain (hazard ratio 0.49; 95% confidence interval 0.32 to 0.76; p = 0.001). Furthermore, among patients classified as appropriate by the AUC, Seattle Angina Questionnaire scores at 1 month were better in the PCI-treated group compared with the medical therapy group (80 ± 23 vs 75 ± 24 for angina frequency, 73 ± 24 vs 68 ± 24 for physical limitations, and 68 ± 23 vs 60 ± 24 for quality of life; all p <0.01), with differences generally persisting through 12 months. In contrast, health status scores were similar throughout the first year of follow-up in PCI + OMT patients compared with OMT alone in patients classified as uncertain or inappropriate. In conclusion, these findings support the validity of the AUC in efforts to improve health care quality through optimal use of PCI.