High pressure synthesis of late rare earth RFeAs(O,F) superconductors; R = Tb and Dy.

New TbFeAs(O,F) and DyFeAs(O,F) superconductors with critical temperatures T(c) = 46 and 45 K and very high critical fields, >or=100 T, have been prepared at 1100-1150 degrees C and 10-12 GPa, demonstrating that high pressure may be used to synthesise late rare earth derivatives of the recently reported RFeAs(O,F) (R = La-Nd, Sm, Gd) high temperature superconductors.

Abciximab readministration: results of the ReoPro Readministration Registry.

BACKGROUND: Platelet glycoprotein IIb/IIIa blockade with abciximab (ReoPro) improves the clinical outcomes of percutaneous coronary intervention. This registry was conducted to characterize the effects of repeated administration of abciximab during intervention. METHODS AND RESULTS: We recruited 500 consecutive patients at 22 centers in the United States who were receiving abciximab for at least a second time during percutaneous coronary intervention. Safety was measured as the incidence of hypersensitivity reactions, major bleeding, and thrombocytopenia. Efficacy was assessed as event-free clinical success. Human antichimeric antibody (HACA) responses were also characterized. There were no cases of hypersensitivity (95% upper confidence bound, 0.3%), major bleeding, or death. Clinical success was 94.4%. Thrombocytopenia occurred in 23 patients (4.6%; 95% CI, 2.8% to 6.4%), including 12 (2.4%; 95% CI, 1.1% to 3.7%) who developed profound thrombocytopenia (<20x10(9) cells/L). In 2 patients (0.4%), profound thrombocytopenia did not develop until after hospital discharge; in 4 (0.8%), profound thrombocytopenia recurred despite platelet transfusion. Before a first readministration, a positive HACA titer was present in 22 of 454 patients (4.8%); after a first readministration, an additional 82 of 432 (19.0%) became HACA-positive. HACA did not neutralize the in vitro inhibition of platelet aggregation by abciximab or correlate with clinical events. CONCLUSIONS: The results, including overall rates of thrombocytopenia, were consistent with randomized clinical trials of first abciximab treatment. However, there was a shift from mild to profound thrombocytopenia, and cases of delayed presentation and of recurrent thrombocytopenia were seen. These findings suggest that indications and guidelines for first-time use apply to retreatment, particularly the systematic monitoring for thrombocytopenia.

Rheolytic thrombectomy during percutaneous revascularization for acute myocardial infarction: experience with the AngioJet catheter.

BACKGROUND: Although balloon angioplasty and stenting are effective in the treatment of acute myocardial infarction (MI), reduced coronary flow and distal embolization frequently complicate interventions when thrombus is present. Adjunctive treatment with mechanical thrombectomy devices may reduce these complications. METHODS AND RESULTS: We evaluated the angiographic and clinical outcomes of 70 patients with acute MI (16% with cardiogenic shock) and with angiographically evident thrombus who were treated with AngioJet rheolytic thrombectomy followed by immediate definitive treatment. Procedure success (residual diameter stenosis <50% and Thrombolysis in Myocardial Infarction [TIMI] flow > or =2 after final treatment) was achieved in 93.8%. Clinical success (procedure success without major in-hospital cardiac events) was achieved in 87.5%, with an in-hospital mortality rate of 7.1%. Final TIMI 3 flow was achieved in 87.7%. AngioJet treatment resulted in a mean thrombus area reduction from 73.2 +/- 64.6 mm(2) at baseline to 15.5 +/- 30.1 post-thrombectomy (P <.001). Subsequent definitive treatment included stenting in 67% and balloon angioplasty alone in 26% of patients. Procedural complications included distal embolization in six patients and perforation in two patients. There were no further major adverse events during 30-day follow-up. CONCLUSION: Rheolytic thrombectomy can be performed safely and effectively in patients with acute MI, allowing for immediate definitive treatment in thrombus-containing lesions.

Randomized, placebo-controlled trial of platelet glycoprotein IIb/IIIa blockade with primary angioplasty for acute myocardial infarction. ReoPro and Primary PTCA Organization and Randomized Trial (RAPPORT) Investigators.

BACKGROUND: The benefit of catheter-based reperfusion for acute myocardial infarction (MI) is limited by a 5% to 15% incidence of in-hospital major ischemic events, usually caused by infarct artery reocclusion, and a 20% to 40% need for repeat percutaneous or surgical revascularization. Platelets play a key role in the process of early infarct artery reocclusion, but inhibition of aggregation via the glycoprotein IIb/IIIa receptor has not been prospectively evaluated in the setting of acute MI. METHODS AND RESULTS: Patients with acute MI of <12 hours' duration were randomized, on a double-blind basis, to placebo or abciximab if they were deemed candidates for primary PTCA. The primary efficacy end point was death, reinfarction, or any (urgent or elective) target vessel revascularization (TVR) at 6 months by intention-to-treat (ITT) analysis. Other key prespecified end points were early (7 and 30 days) death, reinfarction, or urgent TVR. The baseline clinical and angiographic variables of the 483 (242 placebo and 241 abciximab) patients were balanced. There was no difference in the incidence of the primary 6-month end point (ITT analysis) in the 2 groups (28.1% and 28.2%, P=0.97, of the placebo and abciximab patients, respectively). However, abciximab significantly reduced the incidence of death, reinfarction, or urgent TVR at all time points assessed (9.9% versus 3.3%, P=0.003, at 7 days; 11.2% versus 5.8%, P=0.03, at 30 days; and 17.8% versus 11.6%, P=0.05, at 6 months). Analysis by actual treatment with PTCA and study drug demonstrated a considerable effect of abciximab with respect to death or reinfarction: 4.7% versus 1.4%, P=0.047, at 7 days; 5.8% versus 3.2%, P=0.20, at 30 days; and 12.0% versus 6.9%, P=0.07, at 6 months. The need for unplanned, "bail-out" stenting was reduced by 42% in the abciximab group (20.4% versus 11.9%, P=0.008). Major bleeding occurred significantly more frequently in the abciximab group (16.6% versus 9.5%, P=0.02), mostly at the arterial access site. There was no intracranial hemorrhage in either group. CONCLUSIONS: Aggressive platelet inhibition with abciximab during primary PTCA for acute MI yielded a substantial reduction in the acute (30-day) phase for death, reinfarction, and urgent target vessel revascularization. However, the bleeding rates were excessive, and the 6-month primary end point, which included elective revascularization, was not favorably affected.

Modifiable risk factors for vascular access site complications in the IMPACT II Trial of angioplasty with versus without eptifibatide. Integrilin to Minimize Platelet Aggregation and Coronary Thrombosis.

OBJECTIVES: This study was designed to identify potential predictors of vascular access site (VAS) complications in the large-scale Integrilin to Minimize Platelet Aggregation and Coronary Thrombosis (IMPACT) II trial, which studied angioplasty with versus without a new glycoprotein (GP) IIb/IIIa receptor inhibitor (eptifibatide). BACKGROUND: GP IIb/IIIa receptor inhibition during coronary interventions has been associated with excess VAS complications. If other predictors of VAS complications could be identified, they might be manipulated to reduce complications. METHODS: A total of 4,010 patients undergoing percutaneous transluminal coronary revascularization (PTCR) were randomized into one of three bolus/20- to 24-h infusion arms: placebo bolus/placebo infusion; 135-microg/kg body weight eptifibatide bolus/0.5-microg/kg per min eptifibatide infusion; or 135-microg/kg eptifibatide bolus/0.75-microg/kg per min eptifibatide infusion. Heparin during the procedure was weight adjusted and stopped 4 h before sheaths were removed. Logistic regression modeling was used to identify independent predictors of VAS complications. RESULTS: VAS complications were more common in patients treated with eptifibatide (9.9% vs. 5.9% placebo-treated patients, p < 0.001). Multivariate analysis identified eptifibatide therapy (p < 0.0001), advanced age (p = 0.0001), longer time to sheath removal (p = 0.0002), stent placement (with intense post-stent anticoagulation) (p = 0.0004), female gender (p = 0.0006), PTCR within 24 h of thrombolytic therapy (p = 0.002), larger heparin doses during PTCR (p = 0.009), major coronary dissection (p = 0.03) and placement of a venous sheath (p = 0.04) as independent predictors of VAS complications. CONCLUSIONS: VAS complications may be reduced by early sheath removal, by avoiding placement of venous sheaths and by limiting heparin dosing to avoid excessive activated clotting times. Early sheath removal during inhibition of platelet aggregation by eptifibatide is feasible.

Clinical characteristics and long-term outcome of patients in whom congestive heart failure develops after thrombolytic therapy for acute myocardial infarction: development of a predictive model.

Ischemic heart disease is the most common cause of congestive heart failure, which often begins after acute myocardial infarction. To better delineate the clinical characteristics and outcomes of patients in whom congestive heart failure develops after acute myocardial infarction in the thrombolytic era, we prospectively evaluated patients enrolled in six of the TAMI trials. The study cohort comprised 1619 consecutive patients who had at least 1 mm of ST-segment elevation in two contiguous electrocardiographic leads within 6 hours of the onset of acute myocardial infarction and who received intravenous thrombolytic therapy. We prospectively collected clinical characteristics, baseline demographics, acute and 1-week angiographic variables, and in-hospital and 1-year outcome data. We performed stepwise multivariable regression analysis to determine the noninvasive and invasive predictors of the development of in-hospital congestive heart failure. Congestive heart failure developed in 301 patients in the hospital (19% of 1521 patients admitted were not in heart failure). These patients were likely to be older and female, have diabetes mellitus and previous myocardial infarction, and have an anterior wall myocardial infarction. On acute angiography, they had lower ejection fractions and a higher incidence of multivessel disease. Patency at 90 minutes was lower in the patients with congestive heart failure, and acute mitral regurgitation occurred in 1.6% versus 0.21% of patients without congestive heart failure. Patients with congestive heart failure had higher mortality, more in-hospital complications, and longer hospitalizations. At 1-year follow up, 21% of the patients in whom congestive heart failure developed had died versus 5% in the group without congestive heart failure. Predictors of new congestive heart failure included increased age, anterior wall myocardial infarction, lower pulse pressure and systolic blood pressure, diabetes mellitus, and the presence of rales on admission. The acute angiographic variables of reduced ejection fraction, increased number of diseased vessels, and attempted percutaneous intervention improved the concordance of the predictive model by 6%. Congestive heart failure remains a common clinical problem after acute myocardial infarction and is associated with a twofold increase in in-hospital morbidity and a fourfold increase in in-hospital and 1-year mortality. The development of congestive heart failure in the hospital can be predicted from noninvasive and invasive baseline characteristics. We present a simple table to predict congestive heart failure from baseline characteristics and invasive information.

Economic implications of the prophylactic use of intraaortic balloon counterpulsation in the setting of acute myocardial infarction. The Randomized IABP Study Group. Intraaortic Balloon Pump.

Intraaortic balloon counterpulsation (IABP) has been shown to improve coronary artery patency and reduce the rates of recurrent myocardial ischemia and its sequelae in selected patients when used within 24 hours of acute myocardial infarction. The economic implications of prophylactic IABP use are unknown. We obtained hospital bills for 102 patients enrolled in the Randomized IABP Trial (56%) and converted charges to costs using each hospital's Medicare cost report. In-hospital costs for patients who had 48 hours of IABP were compared with those of patients who did not. The costs of angiographic and clinical complications were determined. Small differences in clinical and angiographic characteristics existed between patients in the economic substudy and the overall population, but overall angiographic and clinical outcomes were comparable. Costs for patients who had IABP versus control patients were similar: mean $22,357 +/- $14,369 versus $19,211 +/- $8,414, median (25th and 75th percentiles) $17,903 ($15,787, $22,147) versus $17,913 ($15,144, $21,433), p = 0.45. Hospital costs were higher with the development of recurrent ischemia: mean $23,125 +/- $7,690 versus $20,416 +/- $12,449, median $21,069 ($17,896, $26,885) versus $17,492 ($14,892, $20,998) p = 0.02. Patients who had an adverse clinical event (death, stroke, reinfarction, and emergency revascularization) also had higher hospital costs: mean $25,598 +/- $10,024 versus $19,790 +/- $12,045, median $21,877 ($18,380, $28,049) versus $17,364 ($14,773, $20,779), p = 0.002. The prophylactic use of IABP in patients at high risk of infarct artery reocclusion within 24 hours of acute myocardial infarction provides sustained clinical benefit without substantially increasing hospital costs.

Frequency, significance, and cost of recurrent ischemia after thrombolytic therapy for acute myocardial infarction. TAMI Study Group.

Early postinfarction angina implies an unfavorable prognosis. Most published information on this outcome represents data collected in the prethrombolytic era, in which definitions and populations differed considerably. Our purpose was to evaluate the incidence and importance of recurrent ischemia after administration of thrombolytic therapy. We studied patients enrolled in the Thrombolysis and Angioplasty in Myocardial Infarction studies. Patients were enrolled into 5 studies with similar entry criteria; 552 patients were treated with tissue plasminogen activator (t-PA), 293 were treated with urokinase, and 385 received both thrombolytic agents. Recurrent ischemia was defined as symptoms in association with electrocardiographic changes; reinfarction was defined as a reelevation of creatine kinase myocardial band isoenzyme in an appropriate clinical setting. Both recurrent ischemia and reinfarction occurred in 42 patients (3.4%), recurrent ischemia alone occurred in 226 (18%), whereas neither occurred in 964 (78%). Although baseline characteristics were similar among the 3 groups, in-hospital cardiac events (total 73 deaths, 253 heart failure episodes) were not: in-hospital mortality in patients with reinfarction was 21%; with recurrent ischemia, 11%; and with neither event, 4% (p < 0.0001). The in-hospital heart failure rate of patients with reinfarction was 50%; with recurrent ischemia alone, 31%; and with neither event, 17% (p < 0.0001). As expected, median in-hospital costs were highest in patients with reinfarction ($26,802), intermediate for those with recurrent ischemia alone ($18,422), and lowest in patients with neither event ($15,623). Recurrent myocardial ischemia after thrombolytic therapy is a frequent, important, and expensive adverse clinical outcome, making it a critical target for therapeutic intervention.

Creatine kinase MM and MB isoforms in patients receiving thrombolytic therapy and acute angiography. TAMI Study Group.

Creatine kinase isoforms markers, including MB2 concentration, MB2/MB1 and MM3/MM1 ratios, and MT index (based on the "tissue" M subunits), were measured in serial specimens from 207 patients receiving thrombolytic therapy followed by acute angiography. The slope of release showed a significant relation (P < 0.05) between MB2 concentrations and patency, graded as TIMI 0 through TIMI 3; with regard to the precatheterization/baseline ratio, the MB2 concentrations, the MM3/MM1 ratio, and the MT index were all significantly related to graded patency (P < 0.004). Patients having patency graded as either TIMI 2/3 (Open) or TIMI 0/1 (Closed) showed highly significant differences (P < 0.03) in the slope of release and precatheterization/baseline ratio for all markers except the MB2/MB1 ratio. Defining Open as TIMI 3 and Closed as TIMI 0/1/2 showed very similar results. Despite these significant differences between the Open and Closed groups after thrombolytic therapy, none of the C index calculations (areas under ROC curves) for any of the isoform markers--either alone or combined--exceeded 0.70, suggesting that these markers have limited diagnostic utility for assessing patency.

Effect of cigarette smoking on outcome after thrombolytic therapy for myocardial infarction.

BACKGROUND: Smoking is known to be a strong risk factor for premature atherosclerosis, myocardial infarction, and sudden cardiac death. Unexpectedly, in the reperfusion era, investigators have reported that patients who smoke have a more favorable prognosis after thrombolysis compared with non-smokers. Since smoking is associated with a relatively hyper-coagulable state, we hypothesized that the coronary occlusion responsible for infarction may be primarily thrombotic, with improved outcome relating to enhanced patency or the absence of a residual stenosis after thrombolytic therapy. METHODS AND RESULTS: To examine this issue, we evaluated 1619 patients treated with TPA, urokinase, or both in six consecutive myocardial infarction trials, of whom 878 (54%) were currently smoking. Patients underwent 90-minute and predischarge catheterizations, which were quantified blinded to the patients' smoking status. As expected, baseline fibrinogen (2.8 [2.5,3.6] versus 2.7 [2.4,3.5] g/dL, P = .003) and hematocrit (44% [41%, 47%] versus 43% [40%, 45%], P = .0001) levels were greater in smokers. Although there were no differences between smokers and nonsmokers with regard to 90-minute patency (73% versus 74%), smokers were more likely to have TIMI-3 flow (41.1% versus 34.6%, P = .034), with a larger minimum lumen diameter of the infarct stenosis both acutely (0.82 [0.51, 1.11] versus 0.72 [0.43, 1.04] mm, P = .0432) and at follow-up (1.2 [0.8, 1.74] versus 1.0 [0.7, 1.5], P = .002). Although smokers tended to have reduced in-hospital mortality compared with nonsmokers in univariate analysis (4.0% versus 8.9%, P = .0001), after adjustment for baseline differences between smokers and nonsmokers in age (54 [47, 62] versus 60 [54, 68] years, P < .0001), inferior infarct location (60% versus 53%, P < .0001), three-vessel disease (16% versus 22%, P < .001), and baseline ejection fraction (53% [44%, 60%] versus 50% [42%, 58%], P = .0069), smoking history was of no independent prognostic significance. CONCLUSIONS: Therefore, smokers have a relatively hypercoagulable state, documented by increased hematocrit and fibrinogen levels. Quantitative coronary angiographic analysis suggests that the mechanism of infarction in smokers is more often thrombosis of a less critical atherosclerotic lesion compared with nonsmokers. Enhanced perfusion status, as well as favorable baseline clinical and angiographic characteristics, may be responsible for the more benign prognosis of current smokers.

Adjunctive thrombolytic agents with coronary interventional techniques.

Thrombolytics are used in a variety of interventional procedures, including direct lytic therapy, and in conjunction with PTCA, directional atherectomy and intracoronary stenting. The dosage and variety of thrombolytics is controversial. This article examines all potential uses of thrombolytics and reports on major trials using thrombolytics in these situations.

Pharmacodynamics of chimeric glycoprotein IIb/IIIa integrin antiplatelet antibody Fab 7E3 in high-risk coronary angioplasty.

BACKGROUND: Thrombosis has been implicated as central to the clinical complications of coronary angioplasty (PTCA). Chimeric monoclonal 7E3 Fab (c7E3 Fab) is the first of a new class of antiplatelet drugs directed at the platelet glycoprotein IIb/IIIa integrin. This study was performed to determine the pharmacodynamics of c7E3 Fab administration during PTCA and to gain an initial clinical experience with this novel agent. METHODS AND RESULTS: The study was a multicenter, open-label, dose-escalation study conducted in two stages. Enrollment included 56 patients scheduled for elective PTCA who were estimated to be at moderate to high risk of sustaining ischemic complications. All patients were given aspirin and heparin. The study drug was given at least 10 minutes before PTCA. In stage 1, increasing bolus doses of c7E3 Fab were given to 15 patients; a bolus dose of 0.25 mg/kg was found to result in blockade of > 80% of the receptors and reduce platelet aggregation to < 20% compared with baseline, establishing this dose as that necessary to sufficiently suppress platelet activity. In stage 2, additional c7E3 Fab was administered by continuous infusion to 32 patients for progressively longer periods of time (up to 24 hours) to confirm that platelet inhibition could be maintained with prolonged drug infusion. Also, 9 patients otherwise meeting entry criteria were given placebo. There were no thrombotic events among patients receiving c7E3 Fab. Overall procedural and clinical success and complication rates as well as rates of bleeding were statistically similar among groups. However, minor bleeding was more frequent with administration of the active drug. CONCLUSIONS: The novel antiplatelet agent c7E3 Fab can be administered during PTCA in combination with aspirin and heparin. Suppression of platelet activity is dose dependent and can be maintained for up to 24 hours. Further evaluation will be required to determine the extent of improvement in ischemic complication and restenosis rates and to provide additional insight into the safety profile of this potent monoclonal platelet antibody.

Use of aortic counterpulsation to improve sustained coronary artery patency during acute myocardial infarction. Results of a randomized trial. The Randomized IABP Study Group.

BACKGROUND: Aortic counterpulsation has been observed to reduce the rate of reocclusion of the infarct-related artery after patency has been restored during acute myocardial infarction in observational studies. To evaluate the benefit-to-risk ratio of aortic counterpulsation during the early phase of myocardial infarction, a multicenter randomized clinical trial was performed. METHODS AND RESULTS: Patients who had patency restored during acute cardiac catheterization within the first 24 hours of onset of myocardial infarction were randomly assigned to aortic counterpulsation for 48 hours versus standard care. Intravenous heparin was used similarly in both groups and was continued for a median (25th, 75th percentile) of 5 (2,7) days. A total of 182 patients were enrolled; 96 were assigned to aortic counterpulsation and 86 to standard care. Repeat cardiac catheterization was performed at a median of 5 (4,6) days after randomization in 89% of patients assigned to aortic counterpulsation and in 90% of control patients. Patients randomized to aortic counterpulsation had similar rates of severe bleeding complications (2% versus 1%), number of units of blood transfused (mean, 1.3 +/- 2.6 versus 0.9 +/- 1.8 units), and vascular repair or thrombectomy (5% versus 2%) compared with patients treated in a conventional manner. Patients randomized to aortic counterpulsation had significantly less reocclusion of the infarct-related artery during follow-up compared with control patients (8% versus 21%, P < .03). In addition, there was a significantly lower event rate in patients assigned to aortic counterpulsation in terms of a composite clinical end point (death, stroke, reinfarction, need for emergency revascularization with angioplasty or bypass surgery, or recurrent ischemia): 13% versus 24%, P < .04. CONCLUSIONS: This randomized trial showed that careful use of prophylactic aortic counterpulsation can prevent reocclusion of the infarct-related artery and improve overall clinical outcome in patients undergoing acute cardiac catheterization during myocardial infarction.

Randomized evaluation of coronary angioplasty for early TIMI 2 flow after thrombolytic therapy for the treatment of acute myocardial infarction: a new look at an old study. The Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Study Group.

BACKGROUND: Patients who have suffered acute myocardial infarction (AMI) and have been treated with intravenous thrombolytic agents resulting in early 'patent' [Thrombolysis in Myocardial Infarction (TIMI) 2-3 flow grade] arteries have been shown not to benefit from early percutaneous transluminal coronary angioplasty (PTCA). Recent data, however, suggest that the clinical outcome of patients with early TIMI 2 flow is decidedly inferior to that of patients with TIMI 3 flow, raising the question whether early PTCA might be beneficial for patients with TIMI 2 flow. The clinical utility of PTCA for this particular subset of patients has never been assessed. METHODS: We analyzed left ventricular ejection fraction (LVEF) recovery by contrast ventriculography and clinical outcome in Thrombolysis and Angioplasty in Myocardial Infarction Phase I (TAMI-I) study patients with initial TIMI 2 flow grade, determined by blinded core laboratory analysis. RESULTS: No differences were observed between baseline demographic data for the 49 patients randomly assigned to undergo early PTCA compared with that from the 59 patients randomly assigned to receive early medical therapy. Patients were 56 +/- 11 years of age (mean +/- SD), 80% were men, the time from onset of chest pain to catheterization was 268 +/- 71 min, 42% had anterior AMI, and 42% had multivessel disease. Ninety minute baseline LVEF to prehospital discharge LVEF was minimally better in the group randomly assigned to undergo PTCA (51 +/- 12 to 52 +/- 11% versus 55 +/- 10 to 53 +/- 12%, P = 0.06). This contrasted with findings in patients with TIMI 3 flow grade at baseline, which showed a relative benefit for patients randomly assigned to receive early medical therapy (54 +/- 10 to 54 +/- 8% for PTCA, versus 55 +/- 10 to 58 +/- 8% for medical therapy, P = 0.01). Among patients with TIMI 2 flow grade there were no differences in in-hospital death or congestive heart failure (6.1 versus 1.7%, P = 0.25 and 18.4 versus 23.7%, P = 0.50, PTCA versus medical therapy, respectively). CONCLUSION: We conclude that (1) PTCA of infarct-related arteries with TIMI 2 flow grade may modestly improve recovery of left ventricular function, and (2) widespread application of PTCA in this setting should be deferred, pending demonstration that this benefit outweighs the risks of PTCA.

Recombinant human superoxide dismutase (h-SOD) fails to improve recovery of ventricular function in patients undergoing coronary angioplasty for acute myocardial infarction.

BACKGROUND: Animal studies have demonstrated a burst of oxygen free radical generation after reperfusion of ischemic myocardium that could be blocked by administration of the free radical scavenger recombinant human superoxide dismutase (h-SOD). A multicenter, randomized, placebo-controlled clinical trial was designed to test the hypothesis that free radical-mediated reperfusion injury could be reduced by intravenous administration of h-SOD begun before percutaneous transluminal coronary angioplasty (PTCA) in patients with acute transmural myocardial infarction. METHODS AND RESULTS: One hundred twenty patients were randomized to receive placebo (n = 59) or h-SOD (n = 61) given as a 10-mg/kg intravenous bolus followed by a 60-minute infusion of 0.2 mg.kg-1.min-1. Left ventricular function was analyzed via paired contrast left ventriculograms performed before PTCA and after 6 to 10 days and paired radionuclide ventriculograms performed within 24 hours of PTCA and after 4 to 6 weeks. Both h-SOD- and placebo-treated patients showed improvement in global and regional left ventricular function after successful reperfusion. Compared with the placebo group, no additional improvement was observed in the patients treated with h-SOD. CONCLUSIONS: The results of this clinical trial failed to demonstrate a beneficial effect of h-SOD on global or regional left ventricular function in patients who underwent successful PTCA for treatment of acute myocardial infarction.

Randomised trial of coronary intervention with antibody against platelet IIb/IIIa integrin for reduction of clinical restenosis: results at six months. The EPIC Investigators.

Restenosis after coronary angioplasty occurs in at least 30% of patients in the first six months and, as yet, there is no known treatment to decrease this event. We tested a monoclonal antibody Fab fragment (c7E3) directed against the platelet glycoprotein IIb/IIIa integrin, the receptor mediating the final common pathway of platelet aggregation, to see whether it reduced the frequency of clinical restenosis. Patients who had unstable angina, recent or evolving myocardial infarction, or high-risk angiographic morphology, were randomised to receive c7E3 bolus and a 12 hour infusion of c7E3 (708 patients), c7E3 bolus and placebo infusion (695 patients), or placebo bolus and placebo infusion (696 patients). With maintenance of the double-blind state, patients were followed-up for at least 6 months to determine the need for repeat angioplasty or surgical coronary revascularisation and the occurrence of ischaemic events. By 30 days, 12.8% of placebo bolus/placebo infusion patients had had a major ischaemic event (death, myocardial infarction, urgent revascularisation), compared with 8.3% of c7E3 bolus/c7E3 infusion patients, yielding a 4.5% difference (35% reduction, p = 0.008). At 6 months, the absolute difference in patients with major ischaemic event or elective revascularisation was 8.1% between placebo bolus/placebo infusion and c7E3 bolus/c7E3 infusion patients (35.1% vs 27.0%; 23% reduction p = 0.001). The favourable long-term effect was mainly due to less need for bypass surgery or repeat angioplasty in patients with an initial successful procedure, since need for repeat target vessel revascularisation was 26% less for c7E3 bolus/c7E3 infusion than for placebo treatment (16.5% vs 22.3%; p = 0.007). The c7E3 bolus/placebo infusion group had an intermediate outcome which was not significantly better than that of the placebo bolus/placebo infusion group. These results extend the benefit of c7E3 bolus/c7E3 infusion from reducing abrupt closure and acute-phase adverse outcomes to a diminished need for subsequent coronary revascularisation procedures. Because this therapy carries a risk of bleeding complications and has been studied only in high-risk angioplasty patients, further evaluation is needed before it can be applied to other patient groups.

An analysis of the cause of early mortality after administration of thrombolytic therapy. The Thrombolysis Angioplasty in Myocardial Infarction Study Group.

BACKGROUND: The use of thrombolytic therapy in myocardial infarction has been associated with a considerable improvement in survival rate; however, almost 40% of the deaths during hospitalization occur during the first 24 h. Clinical and angiographic characteristics identified through careful comparison of those patients who die early with those who survive may serve as important targets for the development of new strategies for the management of myocardial infarction. METHODS: Medical records and autopsy reports of 810 patients enrolled into four sequential studies evaluating thrombolytic therapy and angioplasty in acute myocardial infarction were reviewed. All patients were enrolled into four similar protocols with administration of thrombolytic therapy (intravenous tissue plasminogen activator in 561 patients, urokinase in 102, and a combination of tissue plasminogen activator and urokinase in 147) and acute cardiac catheterization performed 90 min after starting therapy. RESULTS: The overall in-hospital mortality rate was 6.8% (55 out of 810), with 21 of these deaths (38%) occurring within the first day. The median (25th, 75th percentile) time to death was 3 (0, 12) days. Infarct location was more frequently anterior in patients who died within the first day. Patients who died 24 h after admission to hospital had the lowest patency rate (45%) compared with patients who died within 24 h (59%) and those who survived (71%, P = 0.003). The deaths within the first day were more likely to be a result of cardiogenic shock (48%), ventricular arrhythmias (14%), or cardiac rupture (9%), whereas late deaths were more likely to be a result of recurrent ischemia or reinfarction (32%) and non-cardiac causes (18%). Two patients had an intracranial hemorrhage within the first 24 h which caused immediate death in one and death on the third day of hospitalization in the other. CONCLUSION: Mortality within the first 24 h of thrombolytic therapy administration can be defined by inadequate myocardial reperfusion in patients with cardiac failure, possibly associated reperfusion injury leading to cardiac rupture, and an increased risk of intracranial hemorrhage. These factors may serve as targets for the development of new treatment strategies in acute myocardial infarction that may alter prognosis.