Appropriate invasive and conservative treatment approaches for patients with non-ST-elevation MI

Optional statement Compelling evidence from randomized clinical trials has established the superiority of an early invasive over a conservative management strategy in patients presenting with non-ST-segment acute coronary syndromes, with a 20% to 40% reduction in recurrent ischemic events in patients undergoing routine early angiography and revascularization when appropriate. Those patients at high risk of death, recurrent myocardial infarction, or ischemia as indicated by elevated concentrations of cardiac troponin, ST-segment deviation, or high clinical risk score derive a greater clinical benefit from early invasive management than patients at lower risk who may be managed effectively with either strategy. Patients who have recurrent ischemia, infarction, hemodynamic instability, or a high-risk stress test should be considered for urgent catheterization regardless of the initial strategy chosen.     

A prospective randomized trial of triage angiography in acute coronary syndromes ineligible for thrombolytic therapy: Results of the medicine versus angiography in thrombolytic exclusion (MATE) trial

Objectives. The purpose of this study was to determine if early triage angiography with revascularization, if indicated, favorably affects clinical outcomes in patients with suspected acute myocardial infarction who are ineligible for thrombolysis.Background. The majority of patients with acute myocardial infarction and other acute coronary syndromes are considered ineligible for thrombolysis and therefore are not afforded the opportunity for early reperfusion.Methods. This multicenter, prospective, randomized trial evaluated in a controlled fashion the outcomes following triage angiography in acute coronary syndromes ineligible for thrombolytic therapy. Eligible patients (n = 201) with <24 h of symptoms were randomized to early triage angiography and subsequent therapies based on the angiogram versus conventional medical therapy consisting of aspirin, intravenous heparin, nitroglycerin, beta-blockers, and analgesics.Results. In the triage angiography group, 109 patients underwent early angiography and 64 (58%) received revascularization, whereas in the conservative group, 54 (60%) subsequently underwent nonprotocol angiography in response to recurrent ischemia and 33 (37%) received revascularization (p = 0.004). The mean time to revascularization was 27 ± 32 versus 88 ± 98 h (p = 0.0001) and the primary endpoint of recurrent ischemic events or death occurred in 14 (13%) versus 31 (34%) of the triage angiography and conservative groups, respectively (45% risk reduction, 95% CI 27–59%, p = 0.0002). There were no differences between the groups with respect to initial hospital costs or length of stay. Long-term follow-up at a median of 21 months revealed no significant differences in the endpoints of late revascularization, recurrent myocardial infarction, or all-cause mortality.Conclusions. Early triage angiography in patients with acute coronary syndromes who are not eligible for thrombolytics reduced the composite of recurrent ischemic events or death and shortened the time to definitive revascularization during the index hospitalization. Despite more frequent early revascularization after triage angiography, we found no long-term benefit in cardiac outcomes compared with conservative medical therapy with revascularization prompted by recurrent ischemia.     

Prospective Comparison of Patient Characteristics and Outcome of Non-prior Aspirin Users versus Aspirin Users with Unstable Angina or Non-Q-Wave Myocardial Infarction Treated with Combination Antithrombotic Therapy

The objective of this study was to determine if aspirin users presenting with acute coronary syndromes are at higher risk for subsequent clinical events. In a trial evaluating combination antithrombotic therapy in resting angina or non-Q-wave myocardial infarction (MI), patients were prospectively dichotomized on admission into nonprior versus recent aspirin users. Then 105 nonprior users and 144 users were randomized to treatment with aspirin plus heparin/warfarin for 12 weeks. Recurrent myocardial ischemia occurring during the 12-week follow-up period was defined as recurrent angina (with electrocardiographic changes or prompting coronary revascularization), MI, or death. Prior aspirin users had a significantly higher incidence of previous MI, prior bypass grafting, beta-blocker use, or hypertension (p 0.003) and were more likely to present with unstable angina as opposed to non-Q-wave MI. (p 0.008). The cumulative probability of recurrent ischemic endpoints for nonprior versus recent users was 10% versus 21% at 14 days (log rank p = 0.03), and 19% versus 29%, at 12 weeks (p = 0.06). Using the Cox model, adjusting for variables significantly associated with outcome, aspirin use remained a significant predictor of 14-day outcome (p = 0.04) but not of 12-week outcome (p = 0.06). In conclusion, even after adjusting for significant differences in baseline variables, aspirin users presenting with rest angina or non-Q-infarction have a worse short-term prognosis in spite of maximal medical therapy.     

Balancing benefit against risk in the choice of therapy for coronary artery disease. Lesson from prospective, randomized, clinical trials of percutaneous coronary intervention and coronary artery bypass graft surgery

The ageing world population faces a coming pandemic of high-risk coronary artery disease (CAD). Patients with CAD have 3 therapeutic options, which are based on objective clinical outcome: medical therapy and risk factor modification (Medicine), and 2 forms of revascularization, coronary artery bypass graft surgery (CABG), and percutaneous coronary intervention (PCI). More than 50 large (>100 patients), multicenter, prospective, randomized clinical trials (RCT) have compared these treatment options in terms of clinical benefits and patient risks. The randomized trials which demonstrated hard outcome (survival, myocardial infarction, stroke) benefits from statins, angiotensin-converting enzyme inhibition and thienopyridines have all been completed subsequent to the publication of most Medicine versus revascularization trials. These medical therapies, plus aspirin, beta-blockers, and risk factor modification, should be made available to patients regardless of the decision to revascularize, or the decision by what means (CABG or PCI). This review integrates the information from these trials, comparing the clinical benefits against the risks inherent in the 3 therapeutic options. The results of our review show that: trials of medicine versus revascularization (either CABG or PCI) support the revascularization paradox, in that the patients at highest risk of adverse outcome, from myocardial ischemia, have a hard outcome benefit (survival, MI, or stroke) from revascularization. This paradox, first seen in the Medicine versus CABG trials of the 1970s, is evident in the trials comparing fibrinolysis and other medicines, with primary PCI for ST-elevation myocardial infarction (MI). The paradox is evident in the conservative versus invasive strategy trials of non-ST-elevation MI and unstable angina, where the benefit of revascularization occurs only in high-risk subsets. The paradox often results in sicker patients, who have more to gain from revascularization, being denied it because of the elevated perception of risk (comparable to a reperfusion paradox in ST-elevation MI, where patients most likely to benefit from thrombolytics are denied them because of the perception of risk). Trials that compared medicine with revascularization for the treatment of acute MI support the use of PCI as the preferred early stabilization strategy (90% of all PAMI trial patients). The majority of the PCI versus CABG trials enrolled populations that were at relatively low risk for ischemic clinical events. These trials demonstrated few hard outcome (survival, MI, or stroke) differences between CABG and PCI. On the basis of the results obtained the following conclusions may be drawn: medicines are the primary options for stable, low-risk CAD, and should be given to all CAD patients. Medically refractory is a useful high-risk marker of potential benefit from revascularization. CABG continues to be the complete revascularization option for patients with multivessel, multi-lesion CAD, in part because of its application to chronic occlusions. PCI is the acute stabilization method of choice for patients with on-going ischemia and acute MI, especially among patients with hemodynamic compromise, and/or major comorbidity.     

Interventional therapy of the acute coronary syndromes

The acute coronary syndromes (ACS) have in common rupture of a vulnerable plaque, leading to exposure of the subendothelial surface and plaque core. The resultant thrombosis leads to a variable degree of flow occlusion, the extent of which differentiates the three syndromes and their treatment by percutaneous coronary intervention (PCI). The guiding principle in the decision when to use PCI in the ACS is that the more time critical and high risk the clinical situation, the more likely it is that PCI will improve ultimate outcome. The use of risk stratification by clinical variables can lead to better triage of patients with non–ST-elevation myocardial infarction (MI) and unstable angina between PCI and medical management. Patients presenting with symptoms suggestive of prolonged ischemia should have an electrocardiogram searching for ST changes, a targeted physical, and blood drawn for rapid assay of cardiac enzymes. In the event that ST elevations suggest infarction, while medical therapy is initiated, emergency cardiac catheterization can be organized. PCI in ACS requires adjunctive antiplatelet and antithrombin therapy, and, in general, coronary stenting is advisable. Among patients with non–ST-elevation MI or unstable angina who can be medically stabilized, the presence of high clinical risk scores would favor early coronary angiography. In their absence, medical therapy can be pursued, unless recurrent ischemia occurs. When the patient's condition is stable, evaluation by stress testing can be used to guide further decisions. Copyright 2002, Elsevier Science (USA). All rights reserved.     

Treatment of stable angina.

Severe atherosclerotic narrowing of one or more coronary arteries is responsible for myocardial ischemia and angina pectoris in most patients with stable angina pectoris. The coronary arteries of patients with stable angina also contain many nonobstructive plaques, which are prone to fissures or rupture resulting in presentation of acute coronary syndromes (unstable angina, myocardial infarction, sudden ischemic death). In addition to symptomatic relief of symptoms and an increase in angina-free walking time with antianginal drugs or revascularization procedures, the recent emphasis of treatment has been to reduce adverse clinical outcomes (coronary death and myocardial infarction). The role of smoking cessation, aspirin, treatment of elevated lipids, and treatment of high blood pressure in all patients and of beta-blockers and angiotensin-converting enzyme inhibitors in patients with diminished systolic left ventricular systolic function in reducing adverse outcomes has been well established. What is unknown, however, is whether any anti-anginal drugs (beta-blockers, long-acting nitrates, calcium channel blockers) effect adverse outcomes in patients with stable angina pectoris. Recent trials evaluated the usefulness of suppression of ambulatory ischemia in patients with stable angina pectoris, but it remains to be established whether suppression of ambulatory myocardial ischemia with antianginal agents or revascularization therapy is superior to pharmacologic therapy targeting symptom relief. Patients who have refractory angina despite optimal medical treatment and are not candidates for revascularization procedures may be candidates for newer techniques of transmyocardial revascularization, enhanced external counterpulsation, spinal cord stimulation, or sympathectomy. The usefulness of these techniques, however, needs to be confirmed in large randomized clinical trials.     

Diagnosis, incidence, and clinical significance of early postoperative ischemia after transmyocardial laser revascularization.

BACKGROUND: Clinical improvement after transmyocardial laser revascularization (TMR) is typically delayed, and patients therefore remain at risk for ischemic events after the procedure. The purpose of this study was to define the range of creatine phosphokinase (CPK) and CPK-MB enzyme elevation after TMR and to assess the incidence of early postoperative ischemic events. METHODS: Twenty-one patients undergoing isolated TMR were evaluated for 48 hours after surgery with serial CPK and CPK-MB enzymes and 12-lead electrocardiograms for evidence of myocardial ischemia or injury. Clinically evident postoperative ischemic events including angina pectoris, myocardial infarction (MI), and cardiac death were recorded as well. RESULTS: Eleven patients (52.4%) had ischemic electrocardiographic changes in the first 48 hours after TMR. Ischemia was clinically silent in 7 (63.6%) of these 11 patients. Cardiac death occurred in 1 patient (4.8%) as a result of acute MI. Nonfatal MI occurred in an additional 4 patients (19.0%). Of the 5 patients with MI, 4 had angina pectoris versus no angina in the 16 patients without MI (P =.02). All patients had elevated CPK and CPK-MB levels after TMR: however, peak CPK (P =.02) and CPK-MB (P =. 005) levels were significantly higher for patients suffering postoperative MI compared with those without MI. CONCLUSIONS: Transient ischemia occurs frequently after TMR and is clinically silent in the majority of patients. Patients with postoperative MI are more likely to have symptomatic ischemia as well as significant cardiac enzyme elevation. The combination of 12-lead electrocardiogram and cardiac enzymes appears to have significant merit for the diagnosis of myocardial ischemia and infarction after TMR. These studies should be obtained in all patients undergoing TMR for the first 48 hours after surgery.     

Recurrent ischemia during continuous 12-lead ECG-ischemia monitoring in patients with acute coronary syndromes treated with eptifibatide: relation with death and myocardial infarction. PURSUIT ECG-Ischemia Monitoring Substudy Investigators. Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy

Computer-assisted continuous monitoring of the ST-segment allows detection and quantification of recurrent ischemia in patients with acute coronary syndromes. In a substudy of the PURSUIT (Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy) trial, this technique was used to evaluate the effects of the glycoprotein IIb/IIIa inhibitor eptifibatide on the incidence and severity of recurrent ischemia, and to investigate the relationship between recurrent ischemia and the occurrence of subsequent death or myocardial (re)infarction. A total of 258 patients with unstable angina or evolving myocardial infarction without ST elevation were monitored for 24 hours during infusion with either eptifibatide or placebo with a computer-assisted 12-lead ECG-ischemia monitoring device. Recurrent ischemic episodes were identified by an automated computer algorithm. Two hundred and sixteen patients (84%) had ECG recordings suitable for analysis. Ischemic episodes were detected in 35 (33%) of the 105 eptifibatide patients and in 32 (29%) of the 111 placebo patients (not significant). No difference in ischemic burden was apparent between both treatment groups. Patients who exhibited 2 or more episodes of recurrent ischemia more frequently died or suffered a myocardial infarction, both at 7 and 30 days, as well as through the 6-month follow-up. A greater ischemic burden was significantly related to adverse outcome during the 6-month follow-up period. Real-time computer-assisted continuous multilead ECG-ischemia monitoring may help to identify patients with unstable coronary syndromes at increased risk of adverse outcome and, thus, allow for better prognostic triage and more appropriate selection of therapeutic strategies. Integration of these systems in coronary care units and emergency wards should, therefore, be recommended.     

Clinical and prognostic significance of silent myocardial ischemia in survivors after acute myocardial infarction

To clarify the clinical and prognostic significance of silent myocardial ischemia (SMI) after acute myocardial infarction (MI), the clinical characteristics and long-term prognosis after discharge in 525 medically treated survivors after acute MI were investigated. According to the presence of post-infarction angina and results of all exercise tests during hospitalization, 309 patients without ischemic episodes were classified into control group, 59 patients with SMI into SMI group and 157 patients with post-infarction angina into AP group. Previous MI (29%, 24%, 11%, respectively), non-Q wave MI (34%, 34%, 15%) and multivessel disease (69%, 61%, 33%) were more frequent in the SMI and AP groups than in the control group. These indicated clinical characteristics in patients with SMI were similar to those in patients with angina pectoris. The incidence of angina prior to MI onset in patients with SMI was lower than in patients with post-infarction angina. This may suggest that there is some common mechanism keeping them silent in the pre- and post-MI period. During the mean follow-up period of 5.5 years, 93 patients died and 78 had a recurrent MI. Cumulative total and cardiac mortality, and incidence of recurrent MI by actuarial method were higher in the SMI as well as AP group than in the control group. There was no statistically significant difference in prognosis between SMI and AP group. We conclude total ischemic burden, not only symptomatic but SMI, should be treated using currently available therapeutic modalities for further improvement of long-term prognosis in survivors after acute MI.     

Unstable angina: Relationship of clinical presentation,coronary artery pathology,and clinical outcome

Patients with unstable angina are heterogeneous with respect to presentation, coronary artery morphology, and clinical outcome. Subclassification of these patients based on clinical history has been proposed as a means of identifying individuals at increased cardiac risk. We applied such a classification system to 129 patients discharged from a coronary care unit with a diagnosis of acute myocardial ischemia. Patients were then assessed for cardiac events (recurrent angina requiring revascularization, myocardial infarction, death) 12 months following hospital discharge. Patients were classified as recent onset unstable angina preinfarction (n = 42), crescendo unstable angina preinfarction (n = 48), and unstable angina postinfarction (n = 39). Within each of these groups, the patients were further subclassified based on the occurrence of angina on effort, at rest, or both. No attempt was made to subset patients taking antiischemic drugs at the time of clinical presentation to the physician. Coronary angiographic pathology (morphology and number of vessels involved) was similar in the subgroups, but coronary artery thrombus was statistically more likely to be found in patients with crescendo rest angina preinfarction or with frequent anginal episodes at rest postinfarction. Mortality was significantly higher for patients with unstable angina postinfarction (7.7%) than preinfarction (1.1%). No statistical differences were noted between the subgroups with respect to the occurrence of myocardial infarction or recurrent unstable angina requiring revascularization. These data suggest that subclassification of unstable angina patients based on clinical characteristics at presentation is not useful to predict subsequent myocardial infarction or recurrent angina requiring revascularization. However, as one might expect, patients with recurrent angina postinfarction have a higher mortality rate than patients with unstable angina preinfarction, and patients with recurrent rest angina, either pre- or postinfarction, are more likely to have intracoronary thrombus than patients with new onset angina or crescendo effort angina; however, the presence of thrombus did not predict a poor clinical outcome.     

Unstable angina pectoris and non-Q-wave myocardial infarction

Unstable angina pectoris and non-Q-wave myocardial infarction are clinical syndromes that share many pathophysiologic and clinical features. In the spectrum of coronary artery disease, these syndromes lie between chronic stable angina and Q-wave myocardial infarction. Although both conditions are associated with significant morbidity and mortality, patients presenting with these syndromes can be further risk stratified into higher and lower risk based on a number of readily available clinical features and biochemical parameters. Such risk stratification can allow for more tailored treatment and better resource allocation. Although routine early coronary angiography and revascularization has not been shown to be superior to conservative management, certain high-risk patients may benefit from a more aggressive strategy. Medical therapy with the use of antiplatelet, anticoagulant, and antiischemic agents remains the cornerstone of emergent treatment for patients presenting with these syndromes. The recent demonstration of a reduction in both morbidity and mortality with the glycoprotein IIb/IIIa antagonists has further expanded the armamentarium of available agents. Following initial stabilization, risk stratification with stress testing can help identify patients with a large residual ischemic burden who may benefit from coronary angiography with revascularization if feasible.     

Prospective evaluation of the relationship between platelet-leukocyte conjugate formation and recurrent myocardial ischemia in patients with acute coronary syndromes

Platelet-leukocyte conjugates are increased in patients with coronary artery disease but the relationship between conjugate formation and myocardial ischemic outcome is unknown. We prospectively evaluated the relationship between conjugate formation and the development of recurrent myocardial ischemia in patients with acute coronary syndromes (ACS). Platelet-leukocyte conjugate formation (induced by thrombin receptor activating peptide (TRAP)) and platelet aggregation (induced by ADP and arachidonic acid) were assessed in 30 patients with unstable angina or non-ST elevation myocardial infarction. All patients were treated with beta-blockers, aspirin, heparin, and GPIIb-IIIa antagonists and were followed for in-hospital recurrent myocardial ischemia. Troponin I and C-reactive protein (CRP) were also measured. Seven patients (23%) experienced recurrent ischemia. Platelet-neutrophil conjugates were greater in ischemic patients (59 +/- 9 and 36 +/- 4%, P = 0.007, for + ischemia and -ischemia, respectively). Platelet aggregation did not differ between ischemic and nonischemic patients, and there was no significant relationship between aspirin resistance and ischemic outcome. Troponin I was greater in patients who developed recurrent ischemia (3.04 +/- 1.73 vs. 0.70 +/- 0.21 ng/ml, P = 0.03, for +ischemia and -ischemia, respectively) but CRP was not. TRAP-induced platelet-neutrophil conjugate formation was an independent predictor of ischemic outcome (OR 1.07, 95% CI 1.00-1.15, for each 1% increase in conjugate formation). Receiver operator characteristic analysis showed platelet-neutrophil conjugates to have good ability to discriminate between ischemic and nonischemic patients (AUC of 0.84, P < 0.05). TRAP induced platelet-neutrophil conjugate formation is related to in vivo ischemic risk in ACS patients.     

Invasive versus conservative strategy after thrombolytic therapy for acute myocardial infarction in patients with antecedent angina. A report from Thrombolysis in Myocardial Infarction Phase II (TIMI II).

OBJECTIVES. This study was designed to assess the possibility that a subgroup of patients at high risk for recurrent ischemia and reinfarction after thrombolytic therapy might benefit from early intervention. BACKGROUND. The Thrombolysis in Myocardial Infarction Phase II (TIMI II) study recently concluded that an obligatory invasive strategy after thrombolytic therapy offered no advantage over a more conservative strategy. METHODS. Data from the 3,534 patients enrolled in the TIMI II trial were analyzed to determine whether a history of antecedent angina before myocardial infarction identifies patients at high risk for subsequent ischemia and whether these patients might benefit from an invasive strategy. RESULTS. Within the TIMI II population, antecedent angina identified patients at increased risk for recurrent chest pain in the hospital (32.3% vs. 22.1%, p < 0.001) and recurrent infarction during the 1st year of follow-up (11.2% vs. 7.9%, p = 0.001) compared with that of patients without antecedent angina. Among patients assigned to the invasive strategy, coronary arteriography revealed that those with antecedent angina had a more severe residual stenosis of the infarct-related artery after thrombolytic therapy (77.1 +/- 0.7% vs. 73.0 +/- 0.9%, p < 0.001) and more multivessel disease (37.9% vs. 26.4%, p < 0.001). The clinical outcome of the patients with antecedent angina assigned randomly to either the invasive or the conservative strategy were compared. The invasive strategy patients had a slightly lesser incidence of recurrent chest pain in the hospital (29.9% vs. 34.8%, p = 0.13) and more negative (normal) findings on exercise tolerance tests (24.7 vs. 18.9%, p = 0.003), but there was no difference between the treatment strategies in the end point variable of recurrent myocardial infarction or death. CONCLUSIONS. These data demonstrate that antecedent angina identifies patients at increased risk for recurrent ischemic events after thrombolytic therapy. However, similar to the results for the overall population, the invasive strategy does not alter the risk of reinfarction or death compared with the conservative approach.     

Management of post-infarction angina

Post-infarction angina includes a syndrome of ischemic chest pain occurring either at rest or during minimal activity 24 hours or more following an acute MI. It develops in approximately 10 to 15 per cent of patients and is particularly common in non Q-wave infarcts involving the anterior myocardial wall. Post-infarction angina may result from ischemia either within the infarct zone or at a distance and frequently portends a poor long term prognosis. Platelet aggregation, coronary vasospasm, and thrombus formation at the site of a ruptured atherosclerotic plaque are each involved in its pathogenesis. The initial treatment of post-infarction angina includes identification and correction of factors that increase myocardial demand including congestive heart failure and arrhythmias. beta-Adrenergic blockers, calcium channel blockers, and nitrate preparations constitute the first line of medical therapy. The role of heparin is controversial, yet it continues to be used in clinical practice. Although thrombolytic agents are currently being investigated, early experience suggests that they may accelerate clinical stabilization and allow time for elective revascularization when required. Antiplatelet therapy with aspirin has proven benefit in the long term management of unstable angina. Patients unresponsive to medical therapy should be considered for intra-aortic balloon pump placement and early coronary angiography. Revascularization with either coronary angioplasty or coronary artery bypass grafting may then be performed as dictated by the overall clinical status, available facilities, and coronary anatomy.     

Interpretation of new treatment guidelines for non-ST-segment elevation acute coronary syndromes: "ischemia-guided" versus "early invasive" strategies

The American College of Cardiology/American Heart Association Task Force on Practice Guidelines has recently published recommendations regarding the diagnosis and management of patients with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS). Conventional therapy for non-ST-segment elevation acute coronary syndrome (NSTE ACS) has traditionally employed an "ischemia-guided" approach in which diagnostic cardiac catheterization and revascularization are only used in patients with objective-evidence of residual myocardial ischemia as identified by recurrent symptoms or provocative stress testing. More recent studies, however, have demonstrated improved clinical outcomes with the use of an "early invasive" approach, employing routine coronary angiography early in the patient's hospital course, followed by percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery where appropriate. Improved clinical outcomes associated with an "early invasive" strategy may have evolved as a consequence of recent advances in both adjunctive pharmacotherapy and revascularization technique. For example, use of GP IIb/IIIa inhibitors and/or low-molecular-weight heparin prior to catheterization have been shown to reduce clinical events in NSTE ACS patients, and may reduce the risk of an invasive approach by plaque passivation prior to interventional therapy. Perhaps more importantly, the combined use of GP IIb/IIIa inhibitors and intracoronary stenting may reduce the potential early hazard of an invasive approach by specifically decreasing the incidence of death and non-fatal myocardial infarction associated with percutaneous intervention. In spite of the benefits of this synergistic combination of pharmacology and mechanical revascularization, risk stratification remains important in identifying high-risk individuals most likely to benefit from an "early invasive" approach.     

Silent ischemia predicts infarction and death during 2 year follow-up of unstable angina

Silent myocardial ischemia as detected on Holter electrocardiographic (ECG) monitoring is present in greater than 50% of patients with unstable angina despite intensive medical therapy. The presence and the extent of silent ischemia have been correlated with an increased risk of early (1 month) unfavorable outcome including myocardial infarction and need for coronary revascularization for persistent symptoms. Seventy patients with unstable angina who had undergone continuous ECG monitoring for silent ischemia were followed up for 2 years; 37 patients (Group I) had Holter ECG evidence of silent ischemia at bed rest in the coronary care unit during medical treatment with nitrates, beta-receptor blockers and calcium channel antagonists; the other 33 patients (Group II) had no ischemic ST segment changes (symptomatic or silent) on Holter monitoring. Over a 2 year follow-up period, myocardial infarction occurred in 10 patients in Group I (in 2 it was fatal) compared with one nonfatal infarction in Group II (p less than 0.01 by Kaplan-Meier analysis); revascularization with either coronary bypass surgery or angioplasty for symptomatic ischemia was performed in 11 Group I and 5 Group II patients (p less than 0.05). Multivariate Cox's hazard analysis demonstrated that the presence of silent ischemia was the best predictor of 2 year outcome. Therefore, persistent silent myocardial ischemia despite medical therapy in patients with unstable angina carries adverse prognostic implications that persist over a 2 year period.     

Mode and timing of treatment failure (recurrent ischemic events) after hospital admission for non-ST segment elevation acute coronary syndromes

Background Clarification of the specific clinical course of non-ST-segment elevation acute coronary syndromes (NSTEMI ACS), including recurrent ischemic events and need for coronary revascularization, is important given the increasing economic pressure to shorten the length of hospitalization and therefore the duration of acute therapy. To examine the mode and timing of subsequent cardiac events, we analyzed pooled data from the ESSENCE and TIMI 11B studies of antithrombotic therapy in NSTEMI ACS. Methods The daily event rates (with confidence intervals) during the first 43 days and the monthly average event rates during the first year were tabulated for 7081 patients. Results The median antithrombotic treatment duration was 3.2 days, whereas the highest absolute frequency of recurrent angina prompting urgent revascularization, myocardial infarction, or death after hospital admission occurred on day 2, day 3, and day 8, respectively. Coronary revascularization was performed in 32% of patients, with the greatest number occurring on day 4. Only 12% of the end point events were adjudicated as being periprocedural. The median length of hospital stay was 7 days. Conclusions Despite aggressive antithrombotic therapy, a significant proportion of patients with NSTEMI ACS have recurrent ischemia precipitating urgent revascularization or infarction within the first few days, whereas the highest risk of death occurs later, after the first week. (Am Heart J 2002;143:63-9.)     

Holmium laser-assisted coronary angioplasty in acute ischemic syndromes

Background and hypothesis: Initial studies have shown holmium laser to be effective in ablation of coronary atheromam, and small studies suggest that it may be helpful in ablation of thrombotic stenoses. Therefore, holmium laser-assisted coronary angioplasty was studied in 85 consecutive patients with acute ischemia syndromes. Methods: Indications for therapy were acute myocardial infarction (MI) in 7 patients (8%), post-MI ischemic in 32 patients (38%), and crescendo angina pectoris in 46 patients (54%). Coronary morphology characteristics by multivessel angioplasty prognosis group criteria were Type A in 9 (10%), Type B1 in 15 (18%), Type B2 in 44 (52%), Type C in 17 patients (20%). Results: Angiographic evidence of thrombus was seen in 37 (44%) of patients. The laser successfully crossed the total length of the coronary narrowing in 76 patients (89%). Procedure/clinical success was 92% for the total study population, 100% for patients with acute MI, 94% for post-MI ischemia patients, and 89% for patients with crescendo angina. Lesions with and without thrombus had identical procedure succes rates. Major complication rate was 3.5%, (deaths 0%, Q-wave MI 0%, and emergent bypass surgery 3.5%). Six-month angiographic restenosis rate (>50% stenosis) was 45%. Conclusion: Holmium laser-assisted balloon angioplasty appears promising in the treatment of acute ischemic syndromes and thrombotic coronary lesions.     

Recurrent and resistant angina: is the metabolic approach an appropriate answer?

Chronic stable angina is the first manifestation of ischemic heart disease in one half of patients; in the United States, the annual incidence of angina in 213 of 1000 of the population is over 30 years of age. The morbidity associated with ischemic heart disease is considerable: each years millions of patients have an MI, or are hospitalised for unstable angina. In recent years less attention has been paid to chronic ischemic syndrome; a possible explanation is that most patients with angina, refractory to medical treatment, are referred for myocardial revascularization in order to improve symptoms and to prevent death and myocardial infarction. Unfortunately available data do not support this common belief. The current evidence allows us to conclude that percutaneous transluminal coronary angioplasty (PTCA) in chronic coronary artery disease does not reduce the rate of subsequent MI or mortality and that PTCA results in superior symptomatic relief of angina and improved exercise tolerance compared with medical therapy, but the difference narrows with time. Several mechanisms may be considered to explain the persistence of angina/ischemia after a revascularization procedure, including incomplete revascularization, graft/PTCA failure, and disease progression in native coronary arteries. Microvascular dysfunction may play a prominent role in the unexpected prevalence of angina after the removal of obstructions in the major coronary branches. A better understanding of the metabolism derangements associated with ischemia and reperfusion allowed the development of new pharmacological approaches. In contrast to classic "hemodynamic" agents, metabolic agents have no hemodynamic, inotropic or chronotropic effect and interfere with cardiac energy metabolism.     

The Essence Trial: Efficacy and Safety of Subcutaneous Enoxaparin in Unstable Angina and Non-Q-Wave MI: A Double-Blind,Randomized, Parallel-Group,Multicenter Study Comparing Enoxaparin and Intravenous Unfractionated Heparin: Methods and Design

Antithrombotic therapy reduces the risk of recurrent ischemic events in patients with unstable angina. The primary aim of the ESSENCE trial is to evaluate the efficacy of enoxaparin (low molecular weight heparin) versus unfractionated heparin, plus aspirin, in patients with rest angina or non-Q-wave infarction. This is a randomized, double-blind, placebo-controlled study of 3180 patients comparing enoxaparin, 1 mg/kg sc bid, with unfractionated heparin via continuous iv infusion to maintain the aPTT at 2 × control. Patients within 24 hours of the onset of acute myocardial ischemia without ST elevation are eligible, and trial therapy is administered for a minimum of 48 hours to a maximum of 8 days. Primary endpoints analyzed are death, myocardial infarction (MI), or recurrent angina at 14 days. Currently 3019 patients have been randomized in 10 countries. The mean age is 64 years, 33% are female, and 46% have had a prior MI. The overall event rates at 14 days are 1.7% mortality, 5.9% subsequent MI, and 17% recurrent angina. The composite triple endpoint rate is 23.6%. Recruitment should be complete by June 1996. The methods and design of the study are presented in this article.