Effectiveness of percutaneous coronary intervention in patients with silent myocardial ischemia (post hoc analysis of the COURAGE trial)

Previous studies have suggested that percutaneous coronary intervention (PCI) decreases long-term mortality in patients with silent myocardial ischemia (SMI), but whether PCI specifically decreases mortality when added to intensive medical therapy is unknown. We performed a post hoc analysis of clinical outcomes in patients in the COURAGE trial based on the presence or absence of anginal symptoms at baseline. Asymptomatic patients were classified as having SMI by electrocardiographic ischemia at rest or reversible stress perfusion imaging (exercise-induced or pharmacologic). Study end points included the composite primary end point (death or myocardial infarction [MI]); individual end points of death, MI, and hospitalization for acute coronary syndrome; and need for revascularization. Of 2,280 patients 12% (n = 283) had SMI and 88% were symptomatic (n = 1,997). There were no between-group differences in age, gender, cardiac risk factors, previous MI or revascularization, extent of angiographic disease, or ischemia by electrocardiogram or imaging. Compared to symptomatic patients, those with SMI had fewer subsequent revascularizations (16% vs 27%, p <0.001) regardless of treatment assignment and fewer hospitalizations for acute coronary syndrome (7% vs 12%, p <0.04). No significant differences in outcomes were observed between the 2 treatment groups, although there was a trend toward fewer deaths in the PCI group (n = 7, 5%) compared to the optimal medical therapy (OMT) group (n = 16, 11%, p = 0.12). In conclusion, addition of PCI to OMT did not decrease nonfatal cardiac events in patients with SMI but showed a trend toward fewer deaths. Although underpowered, given similar outcomes in other small studies, these findings suggest the need for an adequately powered trial of revascularization versus OMT in SMI patients.     

Optimal medical therapy is a proven option for chronic stable angina

The authors of the meta-analysis of a percutaneous coronary intervention (PCI)-based invasive strategy for improving prognosis for the treatment of angina conclude that a pooling of data from various studies can be sufficiently powered to evaluate the impact of PCI on long-term mortality. However, most randomized coronary artery patient trials have insufficient power to detect significant differences in hard end points. Randomized trials in patients with chronic stable angina enroll few patients who are over age 65 years, have depressed ventricular function, have clinical instability, or who have undergone previous coronary artery bypass grafting (CABG) or PCI. "Medical therapy" today no longer means the absence of PCI, but rather the presence of intensive, evidence-based pharmacologic intervention. The COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive druG Evaluation) trial randomized 2,287 patients to optimal medical therapy alone or optimal medical therapy plus PCI. Optimal medical therapy consisted of antiplatelet therapy, anti-ischemic therapy, and aggressive lipid and blood pressure control. Based on the strength of the evidence, the author of this commentary recommends more-aggressive medical therapy for patients with moderate-to-severe angina, and PCI or CABG for many patients in whom symptoms persist. Optimal medical therapy is a proven option for chronic stable angina.     

The truth and consequences of the COURAGE trial

Percutaneous coronary intervention (PCI) has played an integral role in the therapeutic management strategies for patients who present with either acute coronary syndromes or stable angina pectoris. The COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial enrolled patients with chronic stable angina and at least 1 significant (> or =70%) angiographic coronary stenosis who were randomly assigned to an initial treatment of either PCI in conjunction with optimal medical therapy or optimal medical therapy alone. Although the initial management strategy of PCI did not reduce the risk of death, myocardial infarction, or other major cardiovascular events, improvement in angina-free status and a reduction in the requirement for subsequent revascularization was observed. An in-depth analysis of the COURAGE trial design and execution is provided.     

Percutaneous coronary intervention versus medical therapy for coronary heart disease

Medical therapy reduces myocardial infarction and death in patients with stable coronary heart disease (CHD). In contrast, there is little evidence available to evaluate the impact of percutaneous coronary intervention (PCI) on hard endpoints in such patients. Four randomized, controlled trials have compared PCI with medical therapy. These studies have demonstrated that PCI results in an improvement in angina and exercise tolerance compared with medical therapy, but they also suggest that medical therapy may be preferable to PCI with respect to the risk of cardiac events. Interpretation of these studies has been limited by small sample size, exclusion of high-risk subjects, no or reduced use of stents, lack of a cost-effectiveness evaluation, and absence of risk factor intervention (except for Atorvastatin versus Revascularization Treatment [AVERT], which used aggressive low-density lipoprotein lowering with atorvastatin in the medical group only). The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial will permit better definition of the role of PCI in the treatment of stable or recently stabilized patients with CHD.     

The truth and consequences of the COURAGE trial.

Percutaneous coronary intervention (PCI) has played an integral role in the therapeutic management strategies for patients who present with either acute coronary syndromes or stable angina pectoris. The COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial enrolled patients with chronic stable angina and at least 1 significant (> or =70%) angiographic coronary stenosis who were randomly assigned to an initial treatment of either PCI in conjunction with optimal medical therapy or optimal medical therapy alone. Although the initial management strategy of PCI did not reduce the risk of death, myocardial infarction, or other major cardiovascular events, improvement in angina-free status and a reduction in the requirement for subsequent revascularization was observed. An in-depth analysis of the COURAGE trial design and execution is provided.     

Long-term outcomes of optimized medical management of outpatients with stable coronary artery disease

The objective of this study was to assess long-term clinical outcomes and their correlates in medically managed outpatients with stable angina pectoris, healed myocardial infarction (MI), or documented asymptomatic coronary artery disease (CAD). Management strategy emphasized maximally tolerated medical therapy and modification of coronary risk factors. Referral to invasive coronary interventions followed stricter criteria than standard published guidelines. Primary study outcomes were all-cause mortality or nonfatal myocardial infarction. Secondary study outcomes included cardiac death, unstable angina, or coronary revascularization. A total of 693 men and women with proved CAD (mean age 67 years at entry, 85% men, 41% with history of MI) were enrolled. The annual incidence of nonfatal MI, cardiac mortality, and total mortality was 2.2%, 0.8%, and 1.4%, respectively, during an average follow-up of 4.6 years. Coronary revascularization was performed in 24% of subjects; unstable or progressive anginal symptoms were the most common reasons for revascularization. In patients with documented stable CAD, a management strategy based on intensive medical therapy and modification of established coronary risk factors was associated with excellent long-term outcomes. Thus, coronary interventions can be safely delayed until clinical instability ensues, without increased risk of MI or death. This treatment approach represents a viable alternative to invasive strategies.     

Trials and tribulations associated with angina and traditional therapeutic approaches

Ischemic heart disease is the foremost cause of death in the United States and the developed countries. Stable angina is the initial manifestation of ischemic heart disease in one half of the patients and becomes a recurrent symptom in survivors of myocardial infarction (MI) and other forms of acute coronary syndromes (ACS). There are multiple therapeutic modalities currently available for treatment of anginal symptoms in patients with stable CAD. These include anti‐anginal drugs and myocardial revascularization procedures such as coronary artery bypass graft surgery (CABGS), percutaneous transluminal coronary angioplasty (PTCA) and percutaneous coronary intervention (PCI). Anti‐anginal drug therapy is based on treatment with nitrates, beta blockers, and calcium channel blockers. A newly approved antianginal drug, ranolazine, is undergoing phase III evaluation. Not infrequently, combination therapy is often necessary for adequate symptom control in some patients with stable angina. Howerever, there has not been a systematic evaluation of individual or combination antianginal grug therapy on hard clinical end points in patients with stable angina. Most revascularization trials that have evaluated treatment with CABGS, PTCA, or PCI in patients with chronic CAD and stable angina have not shown significant improvement in survival or decreased incidence of non‐fatal MI compared to medical treatment. In the CABGS trials, various post‐hoc analyses have identified several smaller subgroups at high‐risk in whom CABGS might improve clinical outcomes. However, there are conflicting findings in different reports and these findings are futher compromised due to the heterogeneous groups of patients in these trials. Moreover, no prospective randomized controlled trial (RCT) has confirmed an advantage of CABGS, compared to medical treatment, in reduction of hard clinical outcomes in any of the high‐risk subgroups. Based on the available data, it appears reasonable to conclude that for most patients (except perhaps in those with presence of left main disease > 50% stenosis) there is no apparent survival benefit of CABGS compared to medical therapy in stable CAD patients with angina. Although these trial have reported better symptom control associated with the revascularization intervention in most patients, this has not been adequately compared using modern medical therapies. Available data from recent studies also suggest treatment with an angiotensin converting enzyme inhibitor (ACEI), a statin and a regular exercise regimen in patients with stable CAD and angina pectoris. Copyright © 2007 Wiley Periodicals, Inc.     

Seven-year outcome in the RITA-2 trial: coronary angioplasty versus medical therapy

OBJECTIVES: This study was designed to compare the long-term consequences of percutaneous transluminal coronary angioplasty (PTCA) and continued medical treatment. BACKGROUND: The long-term effects of percutaneous coronary intervention need evaluating, especially in comparison with an alternative policy of continued medical treatment. METHODS: The Second Randomized Intervention Treatment of Angina (RITA-2) is a randomized trial of PTCA versus conservative (medical) care in 1,018 patients considered suitable for either treatment option. Information on clinical events, interventions, and symptoms is available for a median seven years follow-up. RESULTS: Death or myocardial infarction (MI) occurred in 73 (14.5%) PTCA patients and 63 (12.3%) medical patients (difference +2.2%, 95% confidence interval -2.0% to +6.4%, p = 0.21). There were 43 deaths in both groups, of which 41% were cardiac-related. Among patients assigned PTCA 12.7% subsequently had coronary artery bypass grafts, and 14.5% required additional non-randomized PTCA. Most of these re-interventions occurred within a year of randomization, and after two years the re-intervention rate was 2.3% per annum. In the medical group, 35.4% required myocardial revascularization: 15.0% in the first year and an annual rate of 3.6% after two years. An initial policy of PTCA was associated with improved anginal symptoms and exercise times. These treatment differences narrowed over time, mainly because of coronary interventions in medical patients with severe symptoms. CONCLUSIONS: In RITA-2 an initial strategy of PTCA did not influence the risk of death or MI, but it improved angina and exercise tolerance. Patients considered suitable for PTCA or medical therapy can be safely managed with continued medical therapy, but percutaneous intervention is appropriate if symptoms are not controlled.     

The evolving role of medical therapy for chronic stable angina

The management of chronic stable angina has undergone considerable evolution over the past two decades. This article highlights the need for a comprehensive approach to management that includes carefully identifying cardiac risk factors, using therapeutic lifestyle interventions, aggressive, multifaceted medical therapy, and judiciously using myocardial revascularization. For patients whose ischemia cannot be optimally controlled with traditional anti-ischemic agents, a novel antianginal and anti-ischemic agent (ie, ranolazine) has promise in reducing refractory ischemia as add-on therapy. This article discusses the role of coronary artery bypass graft surgery and percutaneous coronary intervention (PCI) in managing chronic stable angina patients and the clinical implications of the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive drug Evaluation) trial. The combined use of a “focal” approach (PCI to treat the culprit stenosis) and a “systemic” approach (lifestyle intervention and aggressive pharmacotherapy) may afford the best event-free survival and clinical outcomes in patients with stable angina.     

What is the evidence for percutaneous coronary intervention or coronary artery bypass graft in ischemic cardiomyopathy?

Coronary artery disease has supplanted hypertension as the leading cause of congestive heart failure in the United States. The recognition that contraction abnormalities could accrue from gradual stunning, or longer-term 'hibernation,' raised the possibility that revascularization of viable but hypocontractile elements could improve myocardial performance. This review focuses on the data from randomized trials and registries regarding the potential benefits and risks of either coronary artery bypass grafting (CABG) or percutaneous coronary intervention for patients with severe left ventricular dysfunction secondary to coronary artery disease. For patients with medically refractory angina and ischemic cardiomyopathy, revascularization with CABG or percutaneous coronary intervention is recommended. The ongoing National Institutes of Health-sponsored Surgical Treatment for Ischemic Heart Failure (STICH) trial, a multicenter, prospective, randomized trial comparing contemporary medical therapy with CABG for patients with ischemic cardiomyopathy, should provide important information regarding patients who do not have angina. The conclusion of this review is that a trial of medical therapy vs. percutaneous coronary intervention could be of additional value, especially for patients at particularly high risk, when undergoing CABG.     

Comparisons of guideline-recommended therapies in patients with documented coronary artery disease having percutaneous coronary intervention versus coronary artery bypass grafting versus medical therapy only (from the REACH International Registry)

To evaluate current compliance with recommendations for medical therapy in patients with coronary artery disease (CAD), the relation between previous revascularization and use of guideline-recommended therapies was investigated. From 5,400 outpatient practices in 44 countries, we compared baseline characteristics and medical therapy of 40,450 patients with documented CAD (all with previous myocardial infarction, percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG], or angina pectoris) by previous revascularization status. Approximately 33% of patients had previous CABG, 33% had previous PCI, and 33% had no previous revascularization. Patients with previous CABG were older and often men and diabetic. Patients with previous PCI were the youngest. Guideline-recommended medical therapy use was significantly higher in those with previous revascularization. Antiplatelet therapy in medically managed patients was 80% versus 86% and 91% for those with previous CABG or PCI, respectively. Use of any lipid-lowering agent in those with previous CABG or PCI was 86% in the 2 groups versus 70% in patients who were medically managed. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers were used in similar ratios among groups. Previous revascularization appears to be associated with better use of guideline-recommended medical treatment. These trends were similar for patients from the United States versus everywhere else. In conclusion, use of evidence-based, guideline-recommended therapies in outpatients with CAD needs to improve, especially in medically managed patients.     

Gated myocardial perfusion single photon emission computed tomography in the clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial, Veterans Administration Cooperative study no. 424.

BACKGROUND: Stress gated myocardial perfusion single photon emission computed tomography (gSPECT) is increasingly used before and after intercurrent therapeutic intervention and is the basis for ongoing evaluation in the Department of Veterans Affairs clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial. METHODS AND RESULTS: The COURAGE trial is a North American multicenter randomized clinical trial that enrolled 2287 patients to aggressive medical therapy vs percutaneous coronary intervention plus aggressive medical therapy. Three COURAGE nuclear substudies have been designed. The goals of substudy 0 are to examine the diagnostic accuracy of the extent and severity of inducible ischemia at baseline in COURAGE patients compared with patient symptoms and quantitative coronary angiography and to explore the relationship between inducible ischemia and the benefit from revascularization when added to medical therapy. Substudy 1 will correlate the extent and severity of provocative ischemia with the frequency, quality, and instability of recurrent symptoms in postcatheterization patients. Substudy 2 (n = 300) will examine the usefulness of sequential gSPECT monitoring 6 to 18 months after therapeutic intervention. Together, these nuclear substudies will evaluate the role of gSPECT to determine the effectiveness of aggressive risk-factor modifications, lifestyle interventions, and anti-ischemic medical therapies with or without revascularization in reducing patients' ischemic burdens. CONCLUSIONS: The unfolding of evidence on the application of gSPECT in trials such as COURAGE defines a new era for nuclear cardiology. We hope the evidence that emerges from the COURAGE trial will further establish the role of nuclear imaging in the evidence-based management of patients with stable coronary disease.     

The COURAGE trial in perspective

The indications for percutaneous coronary intervention (PCI) continue to evolve because of the steady improvement in technology, broadened patient and lesion selection criteria, and new evidence from clinical trials. Recently, the role of PCI in patients with chronic stable angina has received considerable scrutiny and has been the subject of great controversy. In these patients, the goals of therapy include the relief of symptom, treatment of ischemia, and reducing the need for subsequent interventions. Medical therapy is the cornerstone in the management of coronary artery disease and should be optimized in all patients. The COURAGE trial investigated the efficacy of combined PCI and optimal medical therapy (OMT) versus OMT alone in patients with stable disease. The trial confirmed several issues that have been already well delineated: (1) in low risk patients, the hard endpoints of death and MI are relatively infrequent and are not reduced by PCI – for prevention of these, OMT may be sufficient, (2) crossover from OMT to PCI is frequent, even in low risk patients, (3) PCI is very effective in reducing symptoms and myocardial ischemia, and (4) significant untreated ischemia is associated with greater likelihood of death and MI. © 2008 Wiley‐Liss, Inc.     

左主干病变不同治疗方法的疗效分析

目的　观察不同治疗方法对冠心病左主干病变患者的近期或远期疗效的影响。方法　对我院 1993年至 1998年期间的 10 5 5例冠心病患者分别进行药物治疗、经皮冠状动脉介入术 (PCI)或冠状动脉旁路移植术 (CABG)治疗 ,于 2 0 0 1年 3至 5月对上述患者进行随访 ,平均随访时间 (3 16±1 2 8)年。观察终点包括死亡、非致死性心肌梗死以及再次行心肌血运重建术 (PCI和CABG)。其中左主干病变为 4 2例 ,男 31例 (79 2 % ) ,女 11例。结果　 4 2例左主干病变采用PCI的占 16 6 7% ,CABG占 38 10 % ,药物治疗占 4 5 2 3%。PCI和CABG两组 (n =2 3) ,随访结果均无死亡和心肌梗死 ,药物治疗组 (n =19)有 3例死亡 ,1例急性心肌梗死 (P <0 0 5 )。PCI组有 1例于术后 2个月因心绞痛复发而复查冠状动脉造影 ,结果显示原病变部位发生再狭窄 ,故再次进行冠状动脉搭桥术。单纯药物治疗组有 1例在随访期间行CABG ,两组间的血运重建率没有差异。结论　冠状动脉血运重建对于左主干病变的患者可提高远期生存率 ,减少终点事件的发生。     

Strategies in Stable Ischemic Heart Disease: Lessons from the COURAGE and BARI-2D Trials

There is a continuing debate regarding the most effective strategy for treating stable ischemic heart disease (SIHD). Conflicting data have emerged from several small, randomized controlled trials and meta-analyses regarding the benefits of early revascularization in SIHD. Two recent multicenter, randomized trials, the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial and the Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI-2D) trial, compared two management strategies in SIHD—an initial conservative approach with optimal medical therapy (OMT) versus a strategy of early revascularization in combination with OMT. COURAGE randomized SIHD patients who were candidates for percutaneous coronary intervention (PCI) to either a strategy of early PCI in combination with OMT or OMT alone, whereas BARI-2D randomized diabetic patients with coronary artery disease to either early revascularization (PCI or coronary artery bypass surgery [CABG]) versus OMT. This review examines the principal findings of these trials, with discussion of their strengths, limitations, and applicability to the general population. The results support the hypothesis that in patients with SIHD, early revascularization with PCI in combination with OMT is not superior to OMT alone in reducing mortality and other major cardiovascular events. Subset analysis from BARI-2D did suggest that early CABG, although it did not reduce mortality, significantly reduced the rate of nonfatal myocardial infarction compared with an initial OMT approach. Based on these data, the majority of patients with SIHD should be managed initially with medical therapy, a strategy that is also the most cost effective. Revascularization can be considered for patients with severe or refractory symptoms despite a trial of medical therapy. For diabetic patients who have extensive coronary artery disease, early revascularization with CABG may be reasonable.     

The prognosis in stable and unstable angina

The average annual mortality in unselected patients with chronic stable angina is 4%. Mortality is increased in male patients and in patients who have risk factors such as hypertension, previous MI, or abnormal ECGs. We do not routinely recommend cardiac catheterization in the initial management of patients with stable angina unless the patient exhibits evidence for severe myocardial ischemia on non-invasive testing or has symptoms that are refractory to treatment. In patients who undergo cardiac catheterization, the most important determinant of survival is left ventricular function followed by the number of diseased vessels. Noninvasive testing provides important additional prognostic information to cardiac catheterization data and should be used in the decision to treat a patient medically or surgically. Mortality is increased in patients who have low exercise tolerance, exercise-induced ischemia, or a poor hemodynamic response to exercise. Unstable angina in medically treated patients is associated with a 3% to 5% hospital mortality and 7% to 8% mortality in the first year. The rate of nonfatal MI is about 8% to 10% in the first 2 weeks. We routinely recommend coronary angiography unless patients have had recent cardiac catheterization or there is a major contraindication. Mortality is increased in those who fail to respond to initial therapy, who have severe left ventricular dysfunction, and who have multivessel CAD, particularly left main CAD. The question of whether all patients with unstable angina require coronary angiography for risk stratification and possible revascularization is being addressed in the TIMI III trial.     

Positive treadmill stress tests post myocardial infarction in patients with single-vessel coronary disease

To investigate the possibility that patients with single-vessel coronary artery disease (CAD) and recent myocardial infarction (MI) can have ST segment depression on post infarction treadmill testing due to ischemia, we studied 16 such patients who underwent cardiac catheterization and exercise testing after MI. Of the 11 patients with ST segment depression on treadmill testing, 10 failed to increase their ejection fraction and nine had a focal worsening of wall motion during exercise radionuclide ventriculography. Seven of these 11 patients had hypokinesis or normokinesis in the suspected area of infarction. In contrast, four of the five patients without ST segment depression on treadmill stress testing had an increase in ejection fraction with stress which was significantly greater than that seen in patients with ST depression (7.2% vs 0%, p less than 0.05). Short-term follow-up (1.1 years) revealed continued post infarction angina in 10 of the 11 patients with positive treadmill stress tests. Four of these patients underwent either percutaneous transluminal angioplasty or surgery. We conclude that positive post infarction treadmill tests due to exercise-induced ischemia may occur in patients with single-vessel CAD and may be associated with continued angina that requires surgical intervention.     

Coronary disease in patients with an abdominal aortic aneurysm]

The presence of coronary artery disease (CAD) evaluated with coronary angiography and eventual correction of CAD in abdominal aortic aneurysm (AAA) patients has been considered the main determinant of early and late outcome after AAA repair. This study reports our experience in CAD and AAA patients in terms of diagnosis and therapy of CAD. In a population of 126 patients (122 males, 4 females, mean age 67.5 years, range 37-81) who were candidates to elective repair for AAA with a diameter > or = 5 centimeters, we included coronary arteriography in 1) patients who were symptomatic for angina (15.9%); 2) patients with previous myocardial infarction (33.3%); 3) patients with previous coronary artery bypass (4%). We identified a group of 45 patients (35.7%) with significant CAD who had been treated before AAA surgery by coronary artery bypass grafting (CABG) in 37 cases or percutaneous coronary angioplasty (PTCA) in 8 cases. AAA repair was performed during the same hospital stay or at a later date. We did not report any morbidity and mortality related to cardiac or vascular procedures. We believe that among patients reporting cardiac symptoms (previous myocardial infarction, angina) the incidence of surgically-correctable CAD is not negligible (45/67, 67.2%). Therefore, invasive coronary study is strongly suggested in such cases to reveal and treat an eventual coronary artery stenosis prior to AAA repair. The absence of cardiac morbidity and mortality related to cardiac and vascular procedures supports this approach.     

Impact of ischemia and scar on therapeutic benefit of myocardial revascularization

The question of how to optimally manage coronary artery disease (CAD) has been a challenge for the cardiology community. The results of early, large randomized clinical trials (RCTs) comparing strategies of medical therapy alone versus revascularization plus medical therapy in patients with stable CAD suggested a survival advantage for a revascularization strategy in the setting of more advanced, higher-risk CAD (left main, three-vessel CAD), but a superiority of medical therapy in patients with more limited, relatively lower-risk CAD (one vessel, limited two-vessel CAD). The results of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) and Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trials redefined the management of CAD, supporting the concept that the impact of aggressively applied modern “medical therapy” on patient survival and patient-reported outcomes is not further improved by the addition of percutaneous intervention. On the other hand, RCTs incorporating fractional flow reserve have shown that this physiologic metric can help identify which patients will benefit from a revascularization strategy. This paradigm has been extended to the use of myocardial perfusion imaging-identified ischemia to determine which patients may have enhanced survival with early revascularization versus medical therapy. Although data from a series of observational studies suggest that inducible ischemia on myocardial perfusion scintigraphy can identify revascularization candidates, several studies, including substudies from major RCTs, do not support this idea. Until RCTs comparing revascularization with medical therapy strategies are performed, many questions remain open. The correct thresholds for treatment, the metric to guide treatment, and how revascularization should be performed are as yet undefined.     

Predictive value of C-reactive protein and troponin T in patients with unstable angina: a comparative analysis. CAPTURE Investigators. Chimeric c7E3 AntiPlatelet Therapy in Unstable angina REfractory to standard treatment trial

OBJECTIVES: We evaluated C-reactive protein (CRP) and troponin T (TnT) for predicting six-month cardiac risk in patients with unstable angina. BACKGROUND: Troponin T is predictive of cardiac risk in patients with unstable angina. The clinical implications of elevated CRP in such patients remains controversial. METHODS: Baseline TnT and CRP values were determined in 447 patients with unstable angina enrolled in the placebo group of the Chimeric c7E3 AntiPlatelet Therapy in Unstable angina REfractory to standard treatment trial (CAPTURE) trial. All patients underwent a coronary intervention and were followed for a six month period in which 13 deaths and 47 myocardial infarctions were documented (MIs). RESULTS: Troponin T was >0.1 microg/liter in 30% and CRP was >10 mg/L in 41% of the patients. For the initial 72-h period (including coronary intervention), TnT (17.4% vs. 4.2%; p < 0.001) but not CRP (10.3% vs. 8%; p = 0.41) was predictive of mortality and MI. The TnT-positive patients displayed more frequent recurrent instability before the planned intervention (44.8% vs. 16.9%; p < 0.001), but in the CRP-positive patients, no such increase was observed (25.9% vs. 24.8%; p = 0.92). In contrast, for the six month follow-up period, CRP was predictive of cardiac risk (mortality, MI) (18.9% vs. 9.5%; p = 0.003). Using multivariate analysis, both CRP and TnT emerged as independent predictors of mortality and MI at six-month follow-up. Furthermore, the incidence of coronary restenosis during six-month follow-up was not related to TnT status (3% vs. 4.5%; p = 0.49); however, it was significantly related to CRP status (7% vs. 2.3%; p = 0.03). CONCLUSIONS: Troponin T, but not CRP, was predictive of cardiac risk during the initial 72-h period, whereas CRP was an independent predictor of both cardiac risk and repeated coronary revascularization (coronary artery bypass graft surgery and percutaneous transluminal coronary angioplasty) during six month follow-up.