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.

Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) trial.

The Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) trial was a randomized, multicenter study performed to determine whether immediate or elective (7 day) coronary angioplasty was preferable once infarct vessel recanalization had been confirmed. In addition, a major focus of the effort was to collect detailed information about the clinical course and outcome of all 386 patients entered into the trial, whether randomized or not. This article reports the major end points of acute and follow-up mortality, the incidence and timing of recurrent ischemic events and acute and convalescent infarct-vessel patency. The optimal timing of coronary angioplasty and intravenous tissue plasminogen activator (rt-PA) administration is discussed. The subsets of patients who: 1) were unsuccessfully treated with rt-PA; 2) had a minimal residual (less than 50%) lesion after rt-PA; or 3) underwent emergency coronary bypass surgery are presented. A current practical approach to acute intervention is extrapolated from the TAMI results.

Insights derived from the thrombolysis and angioplasty in myocardial infarction (TAMI) trials.

In the first three phases of Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) multicenter trials, 708 patients received intravenous recombinant tissue-type plasminogen activator (rt-PA) and underwent detailed assessment of clinical, angiographic and ventriculographic outcomes. The cumulative experience and data base afford the opportunity to address several important questions regarding aggressive therapy of myocardial infarction. These include predictive factors of in-hospital mortality, improvement of left ventricular function and the occurrence of recurrent ischemia. Consideration of practical issues, such as thrombolytic therapy for patients with cardiopulmonary resuscitation or previous stroke, use of coronary artery bypass surgery and the effect of operator experience on angioplasty success rate, has also been made possible. The major accomplishments as well as the deficiencies of the current approach to patient management after thrombolysis are reviewed, and the new TAMI trials currently underway are discussed.

Thrombolysis and Angioplasty in Myocardial Infarction (TAMI-1) trial: influence of infarct location on arterial patency, left ventricular function and mortality.

The influence of infarct location on arterial patency, left ventricular function and mortality after 150 mg of intravenous recombinant tissue-type plasminogen activator (rt-PA) and selective coronary angioplasty was studied in 386 patients with acute myocardial infarction. In 329 patients with acute and 1 week angiograms, the 90 min infarct-related artery patency rate after rt-PA in the left anterior descending, the left circumflex and the right coronary artery was 77, 68 and 68%, respectively. Angioplasty, performed in half the patients, resulted in a final acute patency rate of 93%, which was not related to arterial distribution. Repeat catheterization and revascularization were required in 12% of patients before day 7 and were independent of arterial distribution. The reocclusion rate for the right coronary artery (21%) was higher than that for the left anterior descending (12%) or left circumflex (5%) artery (p = 0.01). Acute and 1 week contrast ventriculograms suitable for analysis were available in 266 patients. Whereas serial left ventricular ejection fraction did not improve during the course of this study, serial regional wall motion (centerline chord method) improved in each arterial distribution. The in-hospital mortality rate of 6% was not related to arterial distribution, although death was twice as likely with proximal compared with distal lesions. Ten of 11 patients who died in the group with the left anterior descending artery as the infarct-related artery had a lesion proximal to the first septal perforator branch.(ABSTRACT TRUNCATED AT 250 WORDS)

Precordial ST segment depression predicts a worse prognosis in inferior infarction despite reperfusion therapy. The Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Study Group.

The impact of associated precordial ST segment depression in inferior myocardial infarction on angiographic and clinical outcomes after thrombolytic therapy and selective coronary angioplasty was studied in 583 patients with acute myocardial infarction. Anterior infarction (Group I), inferior infarction with precordial ST segment depression (Group II) and inferior infarction without precordial ST segment depression (Group III) were present in 289, 135 and 159 patients, respectively. Precordial ST segment depression was more frequent in circumflex than right coronary infarct-related arteries (44 [71%] of 62 versus 91 [40%] of 230; p = 0.000). Although acute patency rates were not statistically different, there was a trend toward different patency rates at day 7 (Group I 88%, Group II 84%, Group III 80%; p = 0.089) partly because of insignificantly higher reocclusion rates in inferior infarction without precordial ST segment depression (Group I 11%, Group II 10%, Group III 18%, p = 0.104). Infarct zone regional wall motion (standard deviations/chord) in inferior infarction was lower with precordial ST segment depression, both acutely (Group I -2.8 +/- 0.9, Group II -2.5 +/- 1.2, Group III 2.0 +/- 1.1; p = 0.000) and at day 7 (Group I -2.2 +/- 1.1, Group II -2.3 +/- 1.1, Group III -1.9 +/- 1.3; p = 0.011). Precordial ST segment depression was associated with a lower ejection fraction in inferior infarction both acutely (Group I 47 +/- 11%, Group II 53 +/- 11%, Group III 58 +/- 9%; p = 0.000) and at day 7 (Group I 49 +/- 12%, Group II 53 +/- 10%, Group III 58 +/- 8%; p = 0.000). Complication rates tended to be higher in inferior infarction when precordial ST segment depression was present. Mortality rates for Groups I, II and III were 8%, 6% and 5%, respectively. These results suggest that precordial ST segment depression in inferior infarction predicts a worse ventriculographic and clinical outcome despite reperfusion therapy.

Profound inhibition of platelet aggregation with monoclonal antibody 7E3 Fab after thrombolytic therapy. Results of the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) 8 Pilot Study.

OBJECTIVES: This study was undertaken to establish evidence for physiologic activity and to study the safety of murine-derived monoclonal antibody 7E3 Fab (m7E3 Fab) in patients receiving recombinant tissue-type plasminogen activator (rt-PA). BACKGROUND: Platelet aggregation is believed to be a significant factor in the failure of pharmacologic reperfusion. By binding to the glycoprotein IIb/IIIa receptor, m7E3 Fab inhibits platelet aggregation and has been shown experimentally to decrease the time required for lysis and to prevent reocclusion. However, the safety of profound platelet inhibition after thrombolysis for acute myocardial infarction has not been tested in humans. METHODS: Sixty patients receiving rt-PA, aspirin and heparin for acute myocardial infarction received m7E3 Fab bolus injections in ascending doses at 3, 6 and 15 h after initiation of the thrombolytic infusion. Ten patients treated with rt-PA but not m7E3 Fab were studied as control subjects. RESULTS: Receptor site blockade and inhibition of platelet aggregation to 20 mumol/liter adenosine diphosphate were maximal at a dose of 0.25 mg/kg body weight of m7E3 Fab. Fifteen (25%) m7E3 Fab-treated patients and five (50%) control patients had major bleeding; eight of these events in seven m7E3 Fab-treated patients and one in a control patient occurred at the time of aortocoronary bypass surgery. Recurrent ischemia occurred in eight (13%) m7E3 Fab-treated patients and two (20%) control subjects. Coronary angiography was performed in 43 patients; the infarct-related coronary artery was patent in 5 of 9 (56%) control patients and 34 (92%) of 37 patients receiving m7E3 Fab. CONCLUSIONS: Profound inhibition of platelet aggregation after thrombolysis was associated with bleeding rates comparable to those in control patients and a low rate of recurrent ischemia. The combination of m7E3 Fab and rt-PA, heparin and aspirin appears to be a promising and safe combination that should be evaluated in further studies of patients with acute myocardial infarction.

Accelerated plasminogen activator dose regimens for coronary thrombolysis. The TAMI-7 Study Group.

To determine the clinical profile and efficacy of accelerated recombinant tissue-type plasminogen activator (rt-PA) dose regimens, five different strategies of thrombolytic therapy in a total of 232 patients were systematically evaluated in the setting of acute myocardial infarction. The fifth strategy involved a combination of accelerated rt-PA and intravenous urokinase (regimen E). A weight-adjusted dose of 1.25 mg/kg body weight of tissue plasminogen activator over 90 min (regimen C) yielded the highest coronary patency rate (83%) at acute angiography. The associated in-hospital reocclusion rate for this regimen was low (4%). An exaggerated (60-min) dosage regimen yielded an inferior coronary patency rate (63%). Combination therapy (regimen E) was associated with a 72% patency rate and 3% reocclusion rate. Marginal improvement in global ejection fraction and regional wall function was demonstrated with all strategies by predischarge catheterization. Bleeding complications were most common at the periaccess site and were not different from those in previous experiences reported with conventional 3-h dosing regimens. Measurements of baseline, 30-min and 3-h levels of tissue plasminogen activator, fibrinogen and fibrin(ogen) degradation products were obtained. At 3 h, fibrinogen levels of less than 1 g/liter were demonstrated with combination therapy (regimen E) as well as with regimen C. Major clinical outcomes including death, reocclusion and reinfarction also showed a tendency to be less common with regimen C. Therefore, although accelerated dose regimens of rt-PA do not reliably yield acute coronary patency rates greater than 85%, an acute coronary patency rate of approximately 85% can be approached.(ABSTRACT TRUNCATED AT 250 WORDS)

Lack of impact of early catheterization and fibrin specificity on bleeding complications after thrombolytic therapy. The TAMI Study Group.

OBJECTIVES: The aim of this study was to assess the hemorrhagic risk associated with fibrin-specific thrombolytic therapy and invasive procedures with acute myocardial infarction. BACKGROUND: Successful coronary artery reperfusion has important prognostic implications. Because immediate coronary angiography is the only method proved to differentiate early fibrinolytic success from failure, its use may be important for selected patients. METHODS: Five hundred seventy-five patients were evaluated with six combined thrombolytic and catheterization strategies. Patients were randomized to intravenous urokinase alone, recombinant tissue-type plasminogen activator (rt-PA) alone, or both; simultaneously they were randomized to an immediate versus a deferred catheterization strategy. Hemorrhagic events were assessed. The correlation of hemorrhage with clinical and hemostatic variables was evaluated. Prespecified transfusion criteria were employed. RESULTS: No difference in baseline characteristics or in hemorrhagic complications was noted among the three thrombolytic regimens. Although mild (< 250 ml) bleeding was more common in the group with immediate catheterization, no clinically significant difference among catheterization groups was seen in moderate to life-threatening hemorrhagic events. Most bleeding occurred at vascular access sites, yet severe and life-threatening hemorrhage occurred in < 1% of patients. Baseline and nadir fibrinogen levels, change in baseline fibrinogen levels and peak fibrin and fibrinogen degradation products did not correlate with bleeding risk. A clinical predisposition for bleeding was observed in women as well as older (> or = 65 years) and lighter (< or = 70 kg) patients. With prespecified transfusion criteria, only a minimal increase in blood product usage was noted with immediate catheterization. CONCLUSIONS: Immediate cardiac catheterization can be accomplished without a clinically significant difference in bleeding risk. Fibrin specificity offers no clear advantage in reducing hemorrhagic risk. Bleeding risk correlates best with baseline patient characteristics. Finally, the amount of blood transfused can be reduced with lower transfusion criteria.

Intracoronary stenting compared with conventional therapy for abrupt vessel closure complicating coronary angioplasty: a matched case-control study.

OBJECTIVES: A case-control analysis was performed to compare clinical outcome after intracoronary stenting with that after conventional therapy for abrupt vessel closure. BACKGROUND: Previous studies have demonstrated that stenting after abrupt vessel closure results in marked angiographic improvement and preservation of coronary flow, leading to the anticipation of similar improvement in clinical outcome. METHODS: Sixty-one of 92 consecutive patients treated at two clinical sites by intracoronary stenting for abrupt vessel closure were matched, according to angiographic features of closure and estimated left ventricular mass threatened by ischemia, with patients treated conventionally during the 18 months before stent availability. In 33 pairs of matched patients, vessel closure was established; in 28 pairs, it was threatened (coronary dissection or worsening stenosis with preservation of normal anterograde flow). Baseline clinical and angiographic characteristics were comparable in the two matched groups. Patients with indeterminate mechanisms of total occlusion (31%) or dissections < 15 mm long (43%) predominated; patients with visible thrombus (8%) or dissections > 15 mm long (18%) were infrequently represented. Stents were successfully deployed in 60 of 61 patients at a median of 52 min (range 3 to 269) after the onset of closure. RESULTS: When compared with conventional treatment, stenting resulted in less residual stenosis (26% vs. 49% diameter stenosis, p < 0.001), a greater likelihood of restoration of Thrombolysis in Myocardial Infarction (TIMI) grade 3 blood flow (97% vs. 72%, p < 0.001) and a reduction in the need for emergency bypass surgery (4.9% vs. 18%, p = 0.02). However, the incidence of Q wave myocardial infarction was nearly the same in the two groups (32% vs. 20%, respectively, p = NS). In the group with stenting, peak creatine kinase level and the frequency of Q wave infarction after established vessel closure increased with the time to stent placement (p = 0.001 and 0.054, respectively); the incidence of procedure-related Q wave infarction in patients who underwent stenting within 45 min of closure was very low (3.9%). In-hospital death occurred in 3.3% of patients in each treatment group. At a mean of 6.3 months of follow-up after hospital discharge, survival free from late cardiac death, myocardial infarction, bypass surgery or coronary angioplasty was 74.9% and 81.3% in the stent and the control treatment group, respectively (p = NS). CONCLUSIONS: Although early treatment of established vessel closure by intracoronary stenting was associated with a low incidence of both myocardial infarction and emergency bypass surgery, the likelihood or severity of infarction was not reduced among those in whom stents were implanted later. Patients with threatened vessel closure could not be shown to benefit from stent treatment. These data provide preliminary indications for stent placement in the acute period to be validated in larger randomized studies.

Determinants of the need for early acute intervention in patients treated conservatively after thrombolytic therapy for acute myocardial infarction. TAMI-5 Study Group.

This study sought to determine whether clinical variables can be used to identify patients at high risk of recurrent spontaneous myocardial ischemia or hemodynamic compromise during the 1st 4 days after intravenous thrombolysis for acute myocardial infarction. Of 288 patients randomly assigned to a conservative postthrombolysis strategy, 54 (19%) required urgent cardiac catheterization within 24 h; 75 (26%) underwent urgent cardiac catheterization within 4 days of admission. Of the clinical variables examined by multiple logistic regression analysis, only patient age and anterior wall myocardial infarction correlated with the need for urgent cardiac catheterization (p = 0.0016 and p = 0.017, respectively). Compared with recombinant tissue-type plasminogen activator or urokinase monotherapy, combination therapy with these agents was associated with a lower need for acute intervention during the 1st 24 h after admission, but the difference did not reach statistical significance (14% for combination therapy vs. 21% for each agent alone, p = 0.30). Of the 75 patients undergoing urgent coronary angiography, only 39% had an occluded infarct-related artery. Emergency coronary angioplasty was performed in 49% of the patients and coronary artery bypass graft surgery was performed urgently in 3%. Despite these interventions, the need for urgent cardiac catheterization was associated with an in-hospital mortality rate of 7% (vs. 3% in the group not requiring urgent angiography, p = 0.36); mean left ventricular ejection fraction was 50.5 +/- 11% (vs. 54.3 +/- 10.8%, p = 0.12) and regional infarct zone wall motion was -2.68 +/- 1.07 SD/chord (vs. -2.46 +/- 1.19 SD/chord; p = 0.44).(ABSTRACT TRUNCATED AT 250 WORDS)

Combined tissue-type plasminogen activator and prostacyclin therapy for acute myocardial infarction. Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) 4 Study Group.

Current limitations of recombinant tissue-type plasminogen activator (rt-PA) therapy for acute myocardial infarction include failure to achieve recanalization in 25% of patients, reocclusion and reperfusion injury. Iloprost, a stable analogue of prostacyclin (PGI2), has been demonstrated to facilitate thrombolysis and reduce myocardial stunning in experimental models. To evaluate combined therapy, rt-PA (100 mg 3 h) and Iloprost (2 ng/kg per min for 48 h) were administered to 25 patients and then rt-PA alone (same dose) was given to an additional 25 patients with evolving myocardial infarction. At 90 min after drug administration, infarct-related vessel patency was observed in 11 (44%) of 25 who received rt-PA plus Iloprost compared with 15 (60%) of 25 who received rt-PA alone (p = 0.26). At 1 week, reocclusion had occurred in 3 (14%) of 21 patients who received combined therapy compared with 6 (26%) of 23 patients treated with rt-PA alone (p = 0.46). Ejection fraction increased significantly from baseline to 7 days for rt-PA alone whereas it decreased with combined therapy (rt-PA alone whereas it decreased with combined therapy (rt-PA alone: 47.3 +/- 11.5% at baseline to 50.4 +/- 9.8% at 7 days; rt-PA plus Iloprost: 51.3 +/- 10.1% at baseline to 49.0 +/- 9.4% at 7 days; difference between groups p = 0.05). At 4 h after therapy, fibrinogen decreased 33% for rt-PA plus Iloprost compared with a 52% for rt-PA alone (p = 0.001). Fibrinogen degradation products increased 60% more for rt-PA alone than for rt-PA plus Ilprost. Thus, the combination of rt-PA plus Iloprost at the doses employed did not improve immediate or follow-up coronary artery patency or left ventricular functional recovery compared with that achieved with rt-PA alone.

Emergency coronary artery bypass surgery preserves global and regional left ventricular function after intravenous tissue plasminogen activator therapy for acute myocardial infarction.

Emergency coronary bypass surgery was performed in 24 (6.2%) of 386 consecutive patients enrolled in the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Multicenter Trial. Intravenous tissue plasminogen activator was administered 2.6 +/- 0.7 h and bypass surgery was performed 7.3 +/- 1.9 h after the onset of infarction. Infarct artery patency was achieved in 21 (88%) of the 24 patients (pharmacologically in 18 or mechanically with coronary angioplasty in 3) in the catheterization laboratory before bypass surgery. The indication for surgery was left main or equivalent coronary artery disease in 7 patients, coronary anatomy unsuitable for angioplasty in 4 patients and unsuccessful coronary angioplasty in 13 patients. A coronary perfusion catheter was inserted before surgery in 11 of 13 patients with unsuccessful angioplasty. All three deaths occurred postoperatively in patients with preoperative cardiogenic shock. Three patients required surgical reexploration for postoperative hemorrhage. Comparison of preoperative and predischarge contrast left ventriculograms demonstrated significant preservation of global (left ventricular ejection fraction 49 +/- 6 to 56 +/- 6%; p = 0.008) and regional (standard deviation/chord -2.6 +/- 0.5 to -1.5 +/- 1.1; p = 0.001) left ventricular function. Emergency coronary bypass surgery can be performed with a low morbidity and mortality in patients treated with intravenous tissue plasminogen activator therapy for acute myocardial infarction. Such therapy is associated with significant preservation of global and regional (infarct zone) left ventricular function.

Fate of patients with acute myocardial infarction with patency of the infarct-related vessel achieved with successful thrombolysis versus rescue angioplasty.

Patients with failure of infarct-related artery recanalization after thrombolytic therapy have a poor clinical outcome. These patients have been considered for rescue angioplasty 90 min after thrombolytic therapy at the time of emergency catheterization in the course of five Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) trials. The outcome of 776 patients with patent infarct-related vessels after emergency catheterization was analyzed--607 with thrombolysis-mediated patency of the infarct-related vessel and 169 with patency achieved by angioplasty. Baseline characteristics of the thrombolysis and angioplasty patency groups were similar except for a higher acute left ventricular ejection fraction (51.3% versus 48.2%) in the thrombolysis group (p = 0.003). Seven to 10 day left ventricular ejection fraction was higher (52.3% versus 48.1%), infarct zone functional recovery was greater (0.44 versus 0.21 standard deviation/chord, or 18% versus 7%, p = 0.001) and reocclusion was less (11% versus 21%) in the thrombolysis compared with the angioplasty group. Despite these differences, angioplasty patency was associated with the same low in-hospital mortality rate (5.9% versus 4.6%) and long-term mortality rate (3% versus 2%) as thrombolysis patency. Reocclusion adversely affected the mortality rate and ventricular functional recovery. Technical failure of rescue angioplasty was associated with a much higher mortality rate than was technical success (39.1% versus 5.9%). Thrombolysis patency was preferable to angioplasty patency after thrombolytic therapy in acute myocardial infarction, but both were associated with the same low in-hospital and long-term mortality rates, suggesting that rescue angioplasty is beneficial in some patients with failure of infarct-related artery recanalization after thrombolytic therapy.

Myocardial infarction with minimal coronary atherosclerosis in the era of thrombolytic reperfusion. The Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Study Group.

The incidence of minimal residual atherosclerotic coronary obstruction after successful intravenous thrombolytic therapy was evaluated in 799 patients with acute myocardial infarction. Minimal residual coronary obstruction (less than or equal to 50%) was observed on selective coronary angiography performed 90 min after initiation of thrombolytic therapy in 43 patients (5.5%). In 42 other patients (5.4%), a greater than 50% but less than 100% residual stenosis noted at 90 min demonstrated further resolution of obstruction to less than 50% at an angiographic follow-up study 7 to 10 days later. Patients with minimal residual coronary obstruction were significantly younger (52 +/- 10.7 versus 56.7 +/- 10 years; p = 0.002) and had less multivessel coronary disease (p less than 0.001), better initial left ventricular ejection fraction (54 +/- 12% versus 50.2 +/- 11.4%; p = 0.006) and a lower in-hospital mortality rate (1% versus 7%; p = 0.04) than did patients who had a significant (greater than 50%) residual coronary obstruction after intravenous thrombolysis. Long-term follow-up study of patients with a minimal coronary lesion (average 1.5 +/- 0.6 years) and those with significant residual stenosis (average 1.6 +/- 0.7 years) demonstrated that the incidence of death (2.4% in patients with minimal stenosis versus 3.5% in those with significant stenosis) and recurrent myocardial infarction (5% each) were similar in both groups. New strategies are needed to prevent coronary rethrombosis in patients with minimal atherosclerosis after thrombolytic therapy for acute myocardial infarction.

Mechanism of benefit of combination thrombolytic therapy for acute myocardial infarction: a quantitative angiographic and hematologic study.

OBJECTIVES: The goal of this study was to lend insight into the mechanisms responsible for the beneficial effects of combination thrombolytic therapy. BACKGROUND: Combination thrombolytic therapy for acute myocardial infarction has been associated with less reocclusion and fewer in-hospital clinical events than has monotherapy. METHODS: Infarct-related quantitative coronary dimensions and hemostatic protein levels were evaluated in 287 patients with acute myocardial infarction during the early (90-min) and convalescent (7-day) phases after administration of recombinant tissue-type plasminogen activator (rt-PA), urokinase or combination rt-PA and urokinase. RESULTS: Minimal lumen diameter was similar in the 90-min and 7-day phases after treatment with rt-PA, urokinase and combination rt-PA and urokinase (0.72 +/- 0.45 mm, 0.62 +/- 0.53 mm and 0.75 +/- 0.58 mm, respectively, at 90 min, p = 0.16; and 1.05 +/- 0.56 mm, 1.12 +/- 0.72 mm and 0.94 +/- 0.54 mm, respectively, at 7 days, p = 0.22). In-hospital clinical event and reocclusion rates were less frequent in patients receiving combination therapy than in those receiving monotherapy (25% vs. 38% and 32% for rt-PA and urokinase, respectively, p = 0.084; and 3% vs. 13% and 9% for rt-PA and urokinase, respectively, p = 0.03), but these events were unrelated to early or late coronary dimensions. Patients receiving combination therapy or urokinase monotherapy had significantly higher peak fibrin degradation products (1,307 +/- 860 and 1,285 +/- 898 micrograms/ml vs. 435 +/- 717 micrograms/ml, respectively, p < 0.0001) and lower nadir fibrinogen levels (0.85 +/- 1.00 and 0.75 +/- 0.53 g/liter vs. 1.90 +/- 0.86 g/liter, respectively, p < 0.0001) than did those receiving rt-PA monotherapy. Peak fibrinogen degradation products indirectly correlated (p = 0.004) and baseline (p = 0.026) and nadir (p = 0.089) fibrinogen levels directly correlated with reocclusion. CONCLUSIONS: Lower in-hospital clinical event and reocclusion rates observed with combination thrombolytic therapy may relate to systemic hematologic factors rather than to the residual lumen obstruction after thrombolysis.

Multicenter investigation of coronary stenting to treat acute or threatened closure after percutaneous transluminal coronary angioplasty: clinical and angiographic outcomes.

OBJECTIVES: This study reports on the initial experience with the Gianturco-Roubin flexible coronary stent. The immediate and 6-month efficacy of the device and the incidence of the complications of death, myocardial infarction, emergency coronary artery bypass surgery and recurrent ischemic events are presented. BACKGROUND: Abrupt or threatened vessel closure after coronary angioplasty is associated with increased risk of myocardial infarction, emergency coronary artery bypass graft surgery and in-hospital death. When dissection or prolapse of dilated plaque into the lumen is unresponsive to additional or prolonged balloon catheter inflation, coronary stenting offers a nonsurgical mechanical means to rapidly restore stable vessel geometry and adequate coronary blood flow. METHODS: From September 1988 through June 1991, 518 patients underwent attempted coronary stenting with the 20-mm long Gianturco-Roubin coronary stent for acute or threatened vessel closure after angioplasty. In 494 patients, one or more stents were deployed. Thirty-two percent of patients received stents for acute closure and 69% for threatened closure. RESULTS: Successful deployment was achieved in 95.4% of patients. Overall, stenting resulted in an immediate angiographic improvement in the diameter stenosis from 63 +/- 25% before stenting to 15 +/- 14% after stenting. Emergency coronary artery bypass graft surgery was required in 4.3% (21 of 493 patients). The incidence of in-hospital myocardial infarction (Q wave and non-Q wave) was 5.5% (27 of 493 patients). At 6 months, myocardial infarction was infrequent, occurring in 1.6% (8 of 493 patients). The incidence of in-hospital death was 2.2% (11 of 493 patients). Late death occurred in 7 patients (1.4%) and 34 patients (6.9%) required later bypass graft surgery. Complications included blood loss, primarily from the arterial access site, and subacute thrombosis of the stented vessel in 43 patients (8.7%). CONCLUSIONS: The early multicenter experience suggests that this stent is a useful adjunct to coronary angioplasty to prevent or minimize complications associated with flow-limiting coronary artery dissections previously correctable only by surgery. Although this study was not randomized, it demonstrated a high technical success rate and encouraging results with respect to the low incidence of emergency coronary artery bypass graft surgery and myocardial infarction.

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.

Hemorrhagic complications associated with the use of intravenous tissue plasminogen activator in treatment of acute myocardial infarction.

PURPOSE: Little attention has been paid to the importance of clinical factors associated with bleeding complications caused by the use of thrombolytic agents. The goal of our study was to examine clinical and hematologic factors associated with an increased risk of bleeding in a prospectively observed population that received intravenous tissue plasminogen activator for acute myocardial infarction. PATIENTS AND METHODS: Bleeding complications were evaluated in 386 consecutive patients treated with 150 mg of tissue plasminogen activator over six to eight hours for acute myocardial infarction. All patients also underwent immediate cardiac catheterization. RESULTS: Quantitation of blood loss during the patients' hospital stay included a median drop in hematocrit of 11.4 points, a median nadir hematocrit of 31.2, a 14 percent rate of significant clinically evident bleeding, and a 31 percent rate of transfusion of two or more units of blood. All of these parameters were much more severe in patients treated with coronary artery bypass surgery. Access site hematoma was the most common source of bleeding (45 percent of patients), whereas 8 percent had gastrointestinal bleeding, two patients had retroperitoneal bleeding, and two patients had intracranial bleeding. The median nadir fibrinogen was 1.3 g/liter. Multiple linear regression models were used to investigate the relationship between clinical variables, including multiple hematologic measurements, and measures of the amount of blood loss. The use of coronary artery bypass grafting was the variable most closely associated with hemorrhage. Other invasive procedures (angioplasty and intra-aortic balloon pumping) were also associated with increased bleeding. Among the patient descriptors examined, lighter weight, older age, female sex, and history of hypertension were associated with greater blood loss. Of laboratory coagulation parameters, only nadir fibrinogen levels were significantly associated with more bleeding. CONCLUSION: Careful clinical evaluation may improve assessment of the risk/benefit ratio of thrombolytic therapy.

Correlation between baseline plasminogen activator inhibitor levels and clinical outcome during therapy with tissue plasminogen activator for acute myocardial infarction.

Baseline plasminogen activator inhibitor (PAI) levels were examined for their influence on the responses to thrombolysis with recombinant tissue plasminogen activator (rt-PA) administered for acute myocardial infarction during the Thrombolysis and Myocardial Infarction (TAMI)-I study. Baseline PAI activity was 19 +/- 21 IU/ml (normal less than 5 IU/ml) and baseline PAI-1 antigen 54 +/- 53 ng/ml (normal 27 +/- 16 ng/ml), confirming previous findings of elevated PAI levels during acute myocardial infarction. Among clinical outcomes, lower PAI-1 antigen levels correlated weakly with greater patency at the 90 min angiogram. Thus, high baseline plasma PAI-1 levels may be detrimental to reperfusion with t-PA. There was no correlation with other major in-hospital clinical outcomes including reocclusion at the 7-10 day angiogram, survival to discharge, or bleeding. During the follow up period of 2.0 +/- 0.4 years, no relationship between baseline PAI levels and post-discharge reinfarction was observed.

Comparison of two dose regimens of intravenous tissue plasminogen activator for acute myocardial infarction.

Two dosing schedules of intravenous tissue plasminogen activator (t-PA) for acute myocardial infarction were compared in a multicenter trial. At 2.95 +/- 1.1 hours from onset of chest pain, 386 patients received 150 mg of intravenous t-PA. For the first 178 patients (group A), 60 mg were given in the first-hour dose and the remaining 90 mg were infused over 7 hours. In the subsequent 208 patients (group B), the first-hour dose was 1.0 mg/kg and the remaining 150 mg were given over 5 hours. At initial angiography 94 +/- 30 minutes into therapy, the infarct vessel patency was 64% in group A versus 75% in group B (p = 0.02). By final angiography with up to 4 selective contrast injections, patency was 68% versus 77%, respectively (p = 0.06). Repeat angiography at 7 to 10 days demonstrated reocclusion in 17% of group A and 13% of group B patients (p = 0.35). There was no difference in fibrinogen nadir or mean hematocrit drop between the 2 groups: 120 mg/dl and 11 points, respectively, in group A compared with 120 mg/dl and 10 points in group B. However, bleeding was reduced in group B patients as evident by a decrease in requirement for greater than or equal to 2 units of packed red blood cell transfusion (group A 36%, group B 27%, p = 0.05) and lower incidence of gastrointestinal bleeding (group A 12%, group B 4%, p = 0.002). To further study the importance of weight adjustment, patients were divided into 2 groups according to weight (less than or equal to 90 kg versus greater than 90 kg).(ABSTRACT TRUNCATED AT 250 WORDS)