Background Revascularization rates vary substantially between countries in patients with acute ST-elevation myocardial infarction (STEMI). The impact of early revascularization on clinical outcomes in such patients remains uncertain. The ASSENT-2 fibrinolytic trial provides the opportunity to compare revascularization rates following STEMI in patients across 29 countries, and to explore the relationship between revascularization and clinical outcome.Methods Countries participating in ASSENT-2 were grouped into tertiles according to their in-hospital revascularization rates (<15%, 15-39%, >39%). Baseline characteristics, medication and procedure use, and clinical outcomes of the 16 949 patients enrolled were compared. Multiple Cox regressions were used to assess the relationship between the tertiles and 30-day mortality, the primary endpoint of the ASSENT-2 trial. Multilevel logistic regression models were developed to validate and further extend the findings from the single-level analyses.Results Patients in highest tertile countries were younger, heavier, and more often diabetic or hypertensive. They were more likely to have had a previous myocardial infarction or revascularization procedure. Time to treatment and hospital length of stay were shorter in the highest tertile, and beta-blocker use was more frequent. Stroke rates were low and similar across termites, with no statistically significant difference in rates of intracranial haemorrhage. Recurrent ischaemia and reinfarction were less common in the highest tertile. Mortality rates at 30 days were tower for countries with the highest revascularization rates (5.1% vs 6.9% vs 6.5% for the lower two tertiles, P < 0.001). At 1 year, mortality remained significantly lower in the highest tertile countries (8.4% vs 10.6% vs 9.9%, P = 0.001). Following adjustment for baseline patient characteristics, Cox regression analysis confirmed an excess of 30-day and 1-year mortality in the lowest and intermediate tertiles compared to the highest tertile. The multilevel analyses validated these findings, and demonstrated that a country's life expectancy and the hospital volume were inversely related to both 30-day and 1-year mortality.Conclusions The highest rate of in-hospital revascularization following fibrinolytic therapy for acute myocardial infarction in this international study was associated with a reduction in recurrent ischaemia, reinfarction, and improved survival at both 30 days and at 1 year. The optimal rates of revascularization in this setting remain to be determined. (C) 2003 Published by Elsevier Ltd on behalf of The European Society of Cardiology.

We assessed the relation between baseline electrocardiographic ischemia grades and initial myocardial area at risk (AR) and final infarct size (IS) in 49 patients who had undergone 99mTc sestamibi single-photon emission computed tomography before and 6 ± 1 days after thrombolysis. Patients were classed as having grade III ischemia (ST segment elevation with terminal QRS distortion, n = 19) or grade II ischemia (ST elevation but no terminal QRS distortion, n = 30). We compared AR and IS by baseline ischemia grade and treatment (adenosine vs. placebo) and assessed relations of infarction index (IS/AR ratio ×100) to time to thrombolysis, baseline ischemia grade, and adenosine therapy. Time to thrombolysis was similar for grade II and grade III. For placebo- treated patients, the median AR did not differ significantly between grade II (38%) and grade III patients (46%, p = 0.47), nor did median IS (16 vs. 40%, p = 0.096), but the median infarction index was 66 vs. 90% (p = 0.006). For adenosine-treated patients, median AR (21 vs. 26%, p = 0.44), median IS (5 vs. 17%, p = 0.15), and their ratio (31 vs. 67%, p = 0.23) did not differ significantly between grade II and grade III patients. The infarction index independently related to grade III ischemia (p = 0.0121) and adenosine therapy (p = 0.045). Infarct size related to baseline ischemia grade and was reduced by adenosine treatment. Necrosis progressed slowlier with baseline grade II versus III ischemia, which could offer more time for myocardial salvage with reperfusion.

Background-Trials report a 2% to 6% incidence of reinfarction after fibrinolysis for acute myocardial infarction (MI). We combined the Global Utilization of Streptokinase and Tissue plasminogen activator (alteplase) for Occluded coronary arteries (GUSTO I) and Global Use of Strategies To Open occluded coronary arteries (GUSTO III) populations to better define frequency, timing, and clinical predictors of in-hospital reinfarction.Methods and Results-In 55 911 patients with ST-segment elevation myocardial infarction (MI) who were receiving fibrinolysis, we compared baseline characteristics and mortality rate by reinfarction incidence and developed multivariable logistic regression models to predict in-hospital reinfarction and composite of death or reinfarction. Reinfarction occurred in 2258 patients (4.3%) a median of 3.8 days after fibrinolysis; rates did not differ between GUSTO I (4.0%) and GUSTO III (4.2%) or by fibrinolytic assignment (streptokinase, 4.1%; alteplase, 4.3%; reteplase, 4.5%; combined streptokinase and alteplase, 4.4%; P=0.55). Advanced age, shorter time to fibrinolysis, non-US enrollment, nonsmoking status, prior MI or angina, female sex, anterior MI, and lower systolic blood pressure were associated significantly with reinfarction. Patients with reinfarction had higher mortality at 30 days (11.3% versus 3.5% without reinfarction; odds ratio, 3.5; P<0.001) and from 30 days to 1 year (4.7% versus 3.2%; hazard ratio, 1.5; P<0.001). Significant multivariate predictors of in-hospital death or reinfarction included age, Killip class, systolic and diastolic blood pressures, heart rate, anterior MI, smoking status, prior MI, sex, and country of enrollment (all P<0.001).Conclusion-Reinfarction occurs infrequently after fibrinolysis but confers increased risk of 30-day and 1-year mortality. Some predictors of reinfarction differ from known predictors of death after MI. Improved treatment and prevention strategies for reinfarction deserve study.

BACKGROUND:The grade of ischemia, as detected by the relation between the QRS complex and ST segment on the admission electrocardiogram, is associated with larger infarct size and increased mortality rates in acute myocardial infarction.METHODS:We assessed the correlation between left ventricular function and the admission electrocardiogram in 151 patients with first anterior acute myocardial infarction who received thrombolytic therapy and underwent cardiac catheterization at 90 minutes and before hospital discharge. The number of leads with ST elevation, sum of ST elevation, maximal Selvester score, and the presence of severe (grade 3) ischemia were determined in each electrocardiogram. Left ventricular ejection fraction, the number of chords with wall motion abnormalities, and the severity of dysfunction (SD/chord) were determined.RESULTS:At 90 minutes, the 39 ischemia grade 3 patients had lower ejection fraction than the 112 grade 2 patients. Both at 90 minutes and at hospital discharge, the grade 3 group had more chords with wall motion abnormalities and more severe regional dysfunction (SD/chord). However, the number of leads with ST elevation, sum of ST elevation, and maximal Selvester score had no correlation with ejection fraction at 90 minutes and only mild correlation with the extent of dysfunction (number of chords) at 90 minutes. There was no correlation between either the number of leads with ST elevation or the sum of ST elevation and the severity of regional dysfunction.CONCLUSIONS:The number of leads with ST elevation, sum of ST elevation, and maximal Selvester score had only mild correlation with the extent of myocardial dysfunction but not with the severity of dysfunction. Grade 3 ischemia is predictive of more extensive myocardial involvement and greater severity of regional dysfunction.

We investigated the impact of primary angioplasty compared with thrombolysis in 894 patients with ST elevation acute myocardial infarction and electrocardiographic grades II and III ischemia on enrollment. Patients were divided into 2 groups based on the enrollment electrocardiogram-grade III: (1) absence of an S wave below the isoelectric baseline in leads that usually have a terminal S configuration (leads V(1) to V(3)), or (2) ST J-point amplitude > or =50% of the R-wave amplitude in all other leads. To be included in the grade III group, grade III criteria in > or =2 adjacent leads were required. Patients with ST elevation but without grade III criteria were classified as having grade II. In-hospital mortality was 3.2% and 6.8% in the grade II (n = 616) and grade III (n = 278) groups, respectively (p = 0.016). In the grade II group, in-hospital mortality was similar in the thrombolysis and angioplasty subgroups (3.2% and 3.3%, p = 0.941). In patients with grade III, in-hospital mortality was 6.4% and 7.3%, respectively (p = 0.762). The odds ratio for the grade III group for death with thrombolysis was 2.06 (95% confidence intervals [CI] 0.82 to 5.19; p = 0.125); the odds ratio for primary angioplasty was 2.30 (95% CI 0.93 to 5.66; p = 0.07). In the thrombolysis group, reinfarction occurred in 3.3% and 6.5% of the grade II and grade III subgroups (p = 0.137). In the angioplasty group, reinfarction occurred in 1.3% and 4.4%, respectively (p = 0.239). Grade III ischemia on admission was associated with higher in-hospital and 30-day mortality and a higher rate of reinfarction. There was no difference in mortality between primary angioplasty and thrombolysis in the grade II and grade III ischemia patients.

Background--Early reinfarction after thrombolytic therapy is associated with adverse outcomes and increased mortality. Among patients with reinfarction in the 1992 Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO I) and the 1998 Assessment of the Safety of a New Thrombolytic (ASSENT 2) trials, we investigated temporal and regional differences in the use of repeat thrombolysis, revascularization (angioplasty and/or bypass surgery), or conservative measures and the outcomes of each management strategy.Methods and Results--Data from the 4% of patients (n=2301) who experienced reinfarction after thrombolytic therapy were:studied. Baseline characteristics, 30-day mortality, and incidence of total and hemorrhagic strokes were compared among the 3 treatment groups. The 30-day mortality did not differ between the repeat thrombolysis and revascularization groups (P=0.72), and it was significantly lower among patients treated by these 2 strategies than in those treated conservatively (11% and 11% versus 28%, respectively; P<0.001). Stroke rates did not differ significantly between the 3 treatment strategies (P=0.49). From 1992 to 1998, the percentage of reinfarction patients treated with repeat thrombolysis decreased from 29.3% to 18.5% in US centers and from 51.4% to 41.9% in all other centers (P<0.001). In contrast, use of revascularization procedures increased from 33.5% to 47.9% in US centers and from 8.1% to 23.0% in all other centers (P<0.001).Conclusions--Repeat thrombolysis and revascularization are associated with significantly lower mortality among reinfarction patients. Randomized trials are necessary to assess the exact risks and benefits of rethrombolysis versus interventional revascularization in this subset of high-risk patients presenting with reinfarction after thrombolytic therapy.

BACKGROUND:Fibrinolytic therapy increases the risk of bleeding events. TNK-tPA (tenecteplase) is a variant of rt-PA with greater fibrin specificity and reduced plasma clearance that can be given as a single bolus. We compared the incidence and predictors of bleeding events after treatment with TNK-tPA and rt-PA. METHODS AND RESULTS:In the Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT)-2 trial, 16 949 patients with acute myocardial infarction were randomly assigned a single weight-adjusted bolus of TNK-tPA or a 90-min infusion of rt-PA. A total of 4.66% of patients in the TNK-tPA group experienced major non-cerebral bleeding, in comparison with 5.94% in the rt-PA group (P=0.0002). This lower rate was associated with a significant reduction in the need for blood transfusion (4.25% vs 5.49%, P=0.0003) and was consistent across subgroups. Independent risk factors for major bleeding were older age, female gender, lower body weight, enrolment in the U.S.A. and a diastolic blood pressure <70 mmHg. Females at high risk (age >75 years and body weight <67 kg) were less likely to have major bleeding when treated with TNK-tPA even after other risk factors were taken into account. A total of 0.93% of patients in the TNK-tPA and 0.94% of patients in the rt-PA group experienced an intracranial haemorrhage. Female patients >75 years of age who weighed <67 kg tended to have lower rates of intracranial haemorrhage when treated with TNK-tPA (3/264, 1.14% vs 8/265, 3.02%). CONCLUSIONS:The increased fibrin specificity and single bolus administration of TNK-tPA do not increase the risk of intracranial haemorrhage but are associated with less non-cerebral bleeding, especially amongst high-risk patients.

It is unknown whether the risk factors associated with the development of ventricular septal defect (VSD) after acute myocardial infarction (MI) remain the same when thrombolytic therapy is used, nor have specific electrocardiographic patterns of acute MI associated with the development of VSD been identified. Our study population included patients with an anterior MI enrolled in the GUSTO-I study. Baseline clinical data were collected prospectively for all patients. Patients in whom VSD was suspected by the local investigators at each site were evaluated retrospectively. Baseline clinical and electrocardiographic variables were compared between 2 groups: 10,847 patients without VSD (99.6%) and 48 patients with confirmed VSD (0.4%). Multivariate analysis showed the following clinical variables to be independent predictors of VSD: age (odds ratio [OR] 2.19, 95% confidence intervals [CI] 1.62 to 2.98; p <0.001), female gender (OR 5.07, 95% CI 2.70 to 9.98; p <0.001), and lack of previous angina (OR 2.11, 95% CI 1.12 to 4.29; p = 0.021). Two electrocardiographic variables predicted acute VSD: the magnitude of ST deviation in lead III (OR 1.55, 95% CI 1.12 to 2.21; p = 0.007) and in lead V2 (p <0.001). However, the relation between the ST amplitude in lead V2 and the risk for VSD was nonlinear. In patients with anterior MI who underwent thrombolysis, the risk factors for VSD were age, female gender, and lack of previous angina. Previous infarction was not a risk factor. Less ST-segment depression in lead III was a predictor of VSD.

We assessed the prognostic significance of negative T waves on admission in leads with ST elevation in 2,853 patients with acute myocardial infarction treated with thrombolysis. Patients were classified into 2 groups based on the presence of negative (T–) or positive (T+) T waves in the leads with ST elevation on admission. T+ and T– waves on admission were detected in 2,601 (91%) and 252 (9%) patients, respectively. T– waves were observed in 6.7 and 9.6% of patients admitted ≤2 and 2–6 h after onset of infarction, respectively. There was a difference in prognosis between patients admitted ≤2 and >2 h after symptom onset. T– patients admitted ≤2 h after onset had no hospital mortality (0/52 patients), as compared to a 5.0% mortality rate in T+ patients (36/726 patients; p = 0.19). T– patients treated >2 h after onset suffered higher mortality (20/196 patients; 10.2%) than T+ patients (100/1,836 patients; 5.4%; p = 0.01). Multivariate analysis of the data on patients treated >2 h after onset demonstrated T– waves to be associated with mortality (OR 1.86; 95% CI 1.07–3.25; p = 0.017). T– waves in leads with ST elevation upon admission are associated with adverse prognosis in patients presenting >2 h after symptom onset, whereas in patients presenting ≤2 h after first symptoms, T– waves may be associated with better prognosis.

Background Bolus fibrinolytic therapy facilitates early efficient institution of reperfusion therapy. Tenecteplase is a genetically engineered variant of alteplase with slower plasma clearance, better fibrin specificity, and high resistance to plasminogen-activator inhibitor-1. We did a double-blind, randomised, controlled trial to assess the efficacy and safety of tenecteplase compared with alteplase.Methods In 1021 hospitals, we randomly assigned 16 949 patients with acute myocardial infarction of less than 6 h duration rapid infusion of alteplase (less than or equal to 100 mg) or single-bolus injection of tenecteplase (30-50 mg according to bodyweight). All patients received aspirin and heparin (target activated partial thromboplastin time 50-75 s). The primary outcome was equivalence in all-cause mortality at 30 days.Findings Covariate-adjusted 30-day mortality rates were almost identical for the two groups-6.18% for tenecteplase and 6.15% for alteplase. The 95% one-sided upper boundaries of the absolute and relative differences in 30-day mortality were 0.61% and 10.00%, respectively, which met the prespecified criteria of equivalence (1% absolute or 14% relative difference in 30-day mortality, whichever difference proved smaller). Rates of intracranial haemorrhage were similar (0.93% for tenecteplase and 0.94% for alteplase), but fewer non-cerebral bleeding complications (26.43 vs 28.95%, p=0.0003) and less need for blood transfusion (4.25 vs 5.49%, p=0.0002) were seen with tenecteplase. The rate of death or non-fatal stroke at 30 days was 7.11% with tenecteplase and 7.04% with alteplase (relative risk 1.01 [95% CI 0.91-1.13]).Interpretation Tenecteplase and alteplase were equivalent for 30-day mortality. The ease of administration of tenecteplase may facilitate more rapid treatment in and out of hospital.

This study assessed whether differences in the underlying mechanisms for various patterns of precordial ST-segment depression with inferior acute myocardial infarction (AMI) are associated with poorer prognoses. We studied 1,155 patients with inferior AMI who underwent thrombolysis in the Global Utilization of Streptokinase and TPA for Occluded arteries (GUSTO-I) angiographic substudy: those without precordial ST depression (n = 412; 35.7%), those with maximum ST depression in leads V1 to V3 (n = 547; 47.4%), and those with maximum ST depression in leads V4 to V6 (n = 196; 17.0%) on admission electrocardiogram. We compared the infarct-related artery, presence of left anterior descending or multivessel coronary artery disease, and left ventricular function among groups. Patients with maximum ST depression in leads V4 to V6 more often had 3-vessel disease (26.0%) than those without precordial ST depression (13.5%) or those with ST depression in leads V1 to V3 (15.7%; p = 0.002), and they had a lower ejection fraction (median 54% vs 60% and 55%, respectively; p <0.001). Patients with maximum ST depression in leads V1 to V3 less often had AMIs due to proximal right coronary artery obstruction (23.9%) than patients without precordial ST depression (35.2%) or those with ST depression in leads V4 to V6 (40.0%; p = 0.001) and had larger AMIs as estimated by peak creatine kinase. Different patterns of precordial ST depression are associated with distinctive coronary anatomy. ST depression in leads V4 to V6, but not V1 to V3, confers a greater likelihood of multivessel coronary artery disease.

Background Intracranial hemorrhage is an uncommon but very dangerous complication in patients receiving thrombolytic therapy for acute myocardial infarction. Neurosurgical evacuation is often an available treatment option. However, the association between neurosurgical evacuation and clinical outcomes in these patients has yet to be determined.Methods The GUSTO-I trial randomly assigned 41,021 patients with acute myocardial infarction to 1 of 4 thrombolytic strategies in 1081 hospitals in 15 countries. A total of 268 patients (0.65%) had an intracranial hemorrhage. We assessed differences in clinical characteristics, neuroimaging features, Glasgow coma scale scores, functional status (disabled: moderate or severe deficit; not disabled: no or minor deficit) and 30-day mortality rate between the 46 patients who underwent neurosurgical evacuation and the 222 patients who did not.Results Mortality rate ai 30 days for all patients with intracranial hemorrhage was 60%; an additional 27% were disabled. Evacuation was associated with significantly higher 30-day survival (65% versus 35%, P < .001) and a trend toward improved functional status (nondisabling stroke. 20% versus 12%, P = .15).Conclusions Although intracranial hemorrhage is uncommon oiler thrombolysis for acute myocardial infarction, 87% of patients die or have disabling stroke. Although not definitive, these data indicate that neurosurgical evacuation may be associated with improved clinical outcomes. Physicians treating such patients should consider early neurosurgical consultation and intervention in these patients.

BACKGROUND:Nonhemorrhagic stroke occurs in 0.1% to 1.3% of patients with acute myocardial infarction who are treated with thrombolysis, with substantial associated mortality and morbidity. Little is known about the risk factors for its occurrence.METHODS AND RESULTS:We studied the 247 patients with nonhemorrhagic stroke who were randomly assigned to one of four thrombolytic regimens within 6 hours of symptom onset in the GUSTO-I trial. We assessed the univariable and multivariable baseline risk factors for nonhemorrhagic stroke and created a scoring nomogram from the baseline multivariable modeling. We used time-dependent Cox modeling to determine multivariable in-hospital predictors of nonhemorrhagic stroke. Baseline and in-hospital predictors were then combined to determine the overall predictors of nonhemorrhagic stroke. Of the 247 patients, 42 (17%) died and another 98 (40%) were disabled by 30-day follow-up. Older age was the most important baseline clinical predictor of nonhemorrhagic stroke, followed by higher heart rate, history of stroke or transient ischemic attack, diabetes, previous angina, and history of hypertension. These factors remained statistically significant predictors in the combined model, along with worse Killip class, coronary angiography, bypass surgery, and atrial fibrillation/flutter.CONCLUSIONS:Nonhemorrhagic stroke is a serious event in patients with acute myocardial infarction who are treated with thrombolytic, antithrombin, and antiplatelet therapy. We developed a simple nomogram that can predict the risk of nonhemorrhagic stroke on the basis of baseline clinical characteristics. Prophylactic anticoagulation may be an important treatment strategy for patients with high probability for nonhemorrhagic stroke, but further study is needed.

Background This study assessed the ability of clinical and electrocardiographic variables routinely obtained on admission to identify patients with acute myocardial infarction treated with thrombolytic therapy at risk of early reinfarction.Methods and Results The study included 2602 patients who received thrombolytic therapy for acute myocardial infarction. Baseline demographic variables and admission clinical and electrocardiographic variables were compared between patients with and without reinfarction. Multivariable logistic regression technique was used and included recurrent infarction as the dependent variable, and baseline demographic, clinical, and electrocardiographic variables as independent variables. History of hypertension (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.00 to 2.31) and diabetes mellitus (OR 1.59, 95% CI 1.00 to 2.53) were associated with a higher risk, and current smoking was associated with a lower risk (OR [no versus yes] 1.64, 95% CI 1.05 to 2.58) of early hospital reinfarction. Distortion of the terminal portion of the QRS complex (OR 1.86, 95% CI 1.20 to 2.87) and absence of abnormal Q waves on admission (OR 1.54, 95% CI 0.98 to 2.43) were associated with increased risk of early reinfarction.Conclusions A simple electrocardiographic sign is a reliable predictor of early reinfarction among patients who receive thrombolytic therapy for acute myocardial infarction.

This study assessed the ability of simple clinical and electrocardiographic variables routinely obtained on admission to identify patients who are at high risk of developing high-degree atrioventricular (AV) block during hospitalization in 1,336 patients with inferior wall acute myocardial infarction (AMI). Patients were classified into 2 initial electrocardiographic patterns based on the J-point to R-wave amplitude ratio: pattern 1: those with J point/R wave <0.5 and pattern 2: patients with J point/R wave ≥0.5 in ≥2 leads of the inferior leads II, III, and aVF. High-degree AV block was found in 6.7% of patients (41 of 615) with pattern 1 versus 11.8% of the patients (85 of 721) with pattern 2 on admission electrocardiogram (p = 0.0008). Multivariate logistic regression analysis revealed that the only variables found to be independently associated with high-degree AV block were female gender (odds ratio [OR] 1.48; 95% confidence interval [CI] 0.98 to 2.23; p = 0.06); Killip class on admission ≥2 (OR 2.24; CI 1.43 to 3.51; p = 0.0004); initial electrocardiographic pattern 2 versus pattern 1 (OR 1.82; CI 1.22 to 2.21; p = 0.003); and absence of abnormal Q waves on admission (OR yes vs no 0.68; CI 0.44 to 1.05; p = 0.08). A simple electrocardiographic sign (J point/R wave ≥0.5 in ≥2 leads) is a reliable predictor of the development of advanced AV block among patients receiving thrombolytic therapy for inferior wall AMI.