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.     

The Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Trials: A Decade of Reperfusion Strategies

Beginning with its inception in 1985, the TAMI group performed randomized clinical trials in both academic: and nonacademic settings. The ten TAMI trials not only proved the viability of clinical research in a nontraditional environment, but also contributed significantly to the clinical investigation of acute myocardial infarction through small mechanistic trials. Despite having insufficient power to address overall survival and clinical outcome measures because of patient enrollments ranging from only 50–575 patients, the trials used similar entry criteria and follow-up measures, which permitted broader analyses of the prospectively collected dataset of randomized patients. This article reviews the history of the TAMI collaboration and discusses the findings of the individual trials as well as the contributions of larger analyses to our understanding of patient selection, prognosis, costs, and outcomes. (J Interven Cardiol 1996;9:89–115)     

Determinants of coronary blood flow after thrombolytic administration. TIMI Study Group. Thrombolysis in Myocardial Infarction.

OBJECTIVES: This study evaluated the determinants of coronary blood flow following thrombolytic administration in a large cohort of patients. BACKGROUND: Tighter residual stenoses following thrombolysis have been associated with slower coronary blood flow, but the independent contribution of other variables to delayed flow has not been fully explored. METHODS: The univariate and multivariate correlates of coronary blood flow at 90 min after thrombolytic administration were examined in a total of 2,195 patients from the Thrombolysis in Myocardial Infarction (TIMI) 4, 10A, 10B and 14 trials. The cineframes needed for dye to first reach distal landmarks (corrected TIMI frame count, CTFC) were counted as an index of coronary blood flow. RESULTS: The following were validated as univariate predictors of delayed 90-min flow in two cohorts of patients: a greater percent diameter stenosis (p < 0.0001 for both cohorts), a decreased minimum lumen diameter (p = 0.0003, p = 0.0008), a greater percent of the culprit artery distal to the stenosis (p = 0.03, p = 0.02) and the presence of any of the following: delayed achievement of patency (i.e., between 60 and 90 min) (p < 0.0001 for both cohorts), a culprit location in the left coronary circulation (left anterior descending or circumflex) (p = 0.02, p < 0.0001), pulsatile flow (i.e., reversal of flow in systole, a marker of heightened microvascular resistance, p = 0.0003, p < 0.0001) and thrombus (p = 0.002, p = 0.03). Despite a minimal 16.4% residual stenosis following stent placement, the mean post-stent CTFC (25.8 +/- 17.2, n = 181) remained significantly slower than normal (21.0 +/- 3.1, n = 78, p = 0.02), and likewise 34% of patients did not achieve a CTFC within normal limits (i.e., <28 frames, the upper limit of the 95th percent confidence interval previously reported for normal flow). Those patients who failed to achieve normal CTFCs following stent placement had a higher mortality than did those patients who achieved normal flow (6/62 or 9.7% vs. 1/118 or 0.8%, p = 0.003). CONCLUSIONS: Lumen geometry is not the sole determinant of coronary blood flow at 90 min following thrombolytic administration. Other variables such as the location of the culprit artery, the duration of patency, a pulsatile flow pattern and thrombus are also related to slower flow. Despite a minimal 16% residual stenosis, one-third of the patients treated with adjunctive stenting still have a persistent flow delay following thrombolysis, which carries a poor prognosis.     

Characteristics and outcome of patients in whom reperfusion with intravenous tissue-type plasminogen activator fails: results of the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) I trial

To examine the outcome of patients with persistent coronary artery occlusion despite treatment with intravenous tissue-type plasminogen activator (t-PA), the clinical course of 96 patients with persistent occlusion after 90 min of therapy was evaluated. All patients underwent cardiac catheterization 90 min after initiation of intravenous t-PA. Immediate coronary angioplasty (PTCA) was attempted when the infarct-related artery failed to reperfuse unless the vessel was technically unsuitable or the infarct was thought to be small. No baseline differences could be found between these 96 patients and 288 patients who achieved perfusion with the same protocol. Although patients with and without successful perfusion after t-PA had similar clinical courses before cardiac catheterization, those without perfusion had more complications (ventricular fibrillation, severe bradycardia, hypotension) during catheterization. PTCA achieved reperfusion with less than 50% residual stenosis in 73% of the 86 patients in whom it was attempted, while 16% were left with a high-grade (greater than 50%) residual stenosis and PTCA failed in 11%. Mortality was highest in the nine patients with complete PTCA failure (44%), compared with a 6% mortality in the 63 patients with an insignificant residual stenosis after PTCA and a 14% mortality in the 14 patients with reperfusion, but a greater than 50% residual stenosis after PTCA. In 10 patients with small infarcts (six), unsuitable anatomy (two), or "spontaneous" drug induced (but later) opening before contemplated PTCA (two), PTCA was not attempted and no mortality occurred. The in-hospital reocclusion rate after successful PTCA was 29%, despite the use of heparin and antiplatelet agents.(ABSTRACT TRUNCATED AT 250 WORDS)     

Racial differences in responses to thrombolytic therapy with recombinant tissue-type plasminogen activator. Increased fibrin(ogen)olysis in blacks. The Thrombolysis and Angioplasty in Myocardial Infarction Study Group

To determine whether there are differences in responses to thrombolytic therapy in certain populations, the data for the Thrombolysis and Angioplasty in Myocardial Infarction (phase 1) study were analyzed for black and white patients. Baseline variables including risk factors and extent of coronary artery disease were similar in the 352 white and 24 black patients. The time from onset of chest pain to recombinant tissue-type plasminogen activator (rt-PA) therapy and rt-PA dosing regimens were the same in the two groups. The patency rate of the infarct-related artery at 90 minutes was 91% for blacks and was 72% for whites (p = 0.051). Blacks displayed significantly lower nadir fibrinogen levels (0.57 +/- 0.62 versus 1.3 +/- 0.76 g/l, p less than 0.0001), greater delta fibrinogen (baseline-nadir) (2.7 +/- 1.1 versus 1.7 +/- 1.1 g/l, p less than 0.0001), and increased peak levels of fibrin(ogen) degradation products (837 +/- 865 versus 245 +/- 475 micrograms/ml, p less than 0.0001). rt-PA antigen levels tended to be higher in blacks than in whites (2.8 +/- 2.2 versus 2.2 +/- 3.2 micrograms/ml [p = 0.10] at the peak and 1.6 +/- 1.3 versus 0.99 +/- 1.4 micrograms/ml [p = 0.06] at the end of the maintenance infusion). Major clinical outcomes including survival until time of hospital discharge (92% black versus 93% white, p = 0.68) were not significantly different. However, despite undergoing fewer angioplasty procedures (25% versus 46.3%, p = 0.047), blacks received more transfusions (58.8% versus 19.5% were administered greater than or equal to 2 units packed erythrocytes, p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

A randomized trial of late reperfusion therapy for acute myocardial infarction. Thrombolysis and Angioplasty in Myocardial Infarction-6 Study Group.

BACKGROUND. Experimental and observational clinical studies of acute coronary occlusion have suggested that late reperfusion prevents infarct expansion and facilitates myocardial healing. The purpose of this trial was to assess whether infarct vessel patency could be achieved in late-entry patients and what benefit, if any, can be demonstrated. METHODS AND RESULTS. In a double-blind fashion, 197 patients with 6 to 24 hours of symptoms and ECG ST elevation were randomly assigned to tissue-type plasminogen activator (100 mg over 2 hours) or placebo. Coronary angiography within 24 hours was used to determine infarct vessel patency status. Patients with infarct-related occluded arteries were then eligible for a second randomization to either angioplasty (34 patients) or no angioplasty (37 patients). Ventricular function and cavity size were reassessed at 1 month by gated blood pool scintigraphy and at 6 months by repeat cardiac catheterization. The primary end point, infarct vessel patency, was 65% for plasminogen activator patients compared with 27% in the placebo group (p less than 0.0001). There were no differences between these groups in ejection fraction or infarct zone regional wall motion at 1 or 6 months. At 6 months, infarct vessel patency was 59% in both groups. In the placebo group, there was a significant increase in end-diastolic volume from acute phase of 127 ml to 159 ml at 6-month follow-up (p = 0.006) but no increase in cavity size for the plasminogen activator group patients. Coronary angioplasty was associated with an initial 81% recanalization success and improved ventricular function at 1 month, but by late follow-up no advantage could be demonstrated for this procedure, and there was a 38% spontaneous recanalization rate in the patients assigned to no angioplasty. CONCLUSIONS. The study demonstrates that it is possible to achieve infarct vessel recanalization in the majority of late-entry patients with either thrombolytic therapy or angioplasty. Thrombolytic intervention had a favorable effect on prevention of cavity dilatation and left ventricular remodeling, but there are no late benefits on systolic function after thrombolysis or coronary angioplasty. The conclusions concerning overall potential benefit of applying late reperfusion therapy will require data from large-scale trials designed to assess mortality reduction.     

Risk stratification before thrombolytic therapy in patients with acute myocardial infarction. The Thrombolysis in Myocardial Infarction (TIMI) Phase II Co-Investigators

Several studies in the prethrombolytic era on the treatment of acute myocardial infarction identified selected variables from the patient's history, physical examination, chest roentgenogram and electrocardiogram that could be used to estimate mortality in patients with evolving infarction. To extend such assessment to patients receiving thrombolytic therapy, this study evaluated the prognostic utility of several risk factors in the 3,339 patients (2,742 men, 597 women, aged 24 to 78 years) enrolled in Phase II of the Thrombolysis in Myocardial Infarction (TIMI) trial. Before intravenous tissue plasminogen activator was given, the presence of each of eight risk factors was noted: age greater than or equal to 70 years, female gender, a history of diabetes mellitus or previous myocardial infarction, electrocardiographic evidence of evolving anterior infarction or atrial fibrillation, evidence on physical examination of mild pulmonary congestion or hypotension (systolic pressure less than 100 mm Hg) and sinus tachycardia (heart rate greater than 100 beats/min). Of the 3,339 patients, the 78 with pulmonary edema or cardiogenic shock were excluded because their risk was known to be high. Of the remaining 3,261, 864 (26%) had no risk factor (low risk); their mortality rate at 6 weeks was only 1.5%. In contrast, 2,397 (74%) had one or more risk factors (not low risk); of these, 5.3% died in 6 weeks (p less than 0.001). Among those with one or more risk factors, mortality at 6 weeks was related to the number of risk factors on admission; those with four or more had a mortality rate at 6 weeks of 17.2%. Thus, these eight risk factors can be easily remembered and assessed in patients with myocardial infarction who are candidates for thrombolytic therapy and can be used to estimate short-term mortality.     

Two-year outcome after angiographically documented myocardial reperfusion for acute coronary occlusion. Thrombolysis and Angioplasty Study Group

Reperfusion therapy has been clearly shown to decrease the early mortality after acute myocardial infarction, but the impact of this therapy on long-term survival has been less extensively evaluated. This study reports the extended follow-up of a large cohort of 810 patients treated with intravenous thrombolytic therapy combined, when considered necessary to maintain or augment infarct vessel patency, with mechanical reperfusion therapies. Each patient underwent coronary angiography within 2 hours of the initiation of the thrombolytic infusion. Coronary angioplasty was performed in 62% of the patients before hospital discharge and 21% underwent coronary artery bypass graft surgery. Follow-up was obtained in 96% to a mean of 18.8 months (range, 1.5 to 48 months). All-cause mortality over this period was 3.3%; 2.1% died from cardiac causes. Nonfatal reinfarction occurred in 5.1%. Although the low event rate limits the validity of statistical comparisons, the patients who survived the follow-up period tended to be younger (56 +/- 10 vs 65 +/- 7 years), to have better predischarge left ventricular function (left ventricular ejection fraction, 52 +/- 11 vs 46 +/- 13%) and to have a lower prevalence of multivessel coronary artery disease (45 vs 67%). This excellent long-term survival may, in part, reflect the exclusion of high-risk patients from enrollment in the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) studies. It may also be attributable, however, to the frequent use of combined thrombolysis and mechanical revascularization in this population.     

Immediate versus deferred beta-blockade following thrombolytic therapy in patients with acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI) II-B Study.

In the Thrombolysis in Myocardial Infarction (TIMI) Phase II trial, patients received intravenous recombinant tissue-type plasminogen activator (rt-PA) and were randomized to either a conservative or an invasive strategy. Within this study, the effects of immediate versus deferred beta-blocker therapy were also assessed in patients eligible for beta-blocker therapy, a group of 1,434 patients of which 720 were randomized to the immediate intravenous group and 714 to the deferred group. In the immediate intravenous group, within 2 hours of initiating rt-PA metoprolol was given (5 mg intravenously at 2-minute intervals over 6 minutes, for a total intravenous dose of 15 mg, followed by 50 mg orally every 12 hours in the first 24 hours and 100 mg orally every 12 hours thereafter). The patients assigned to the deferred group received metoprolol, 50 mg orally twice on day 6, followed by 100 mg orally twice a day thereafter. The therapy was tolerated well in both groups and the primary end point, resting global ejection fraction at hospital discharge, averaged 50.5% and was virtually identical in the two groups. The regional ventricular function was also similar in the two groups. Overall, there was no difference in mortality between the immediate intravenous and deferred groups, but in the subgroup defined as low risk there were no deaths at 6 weeks among those receiving immediate beta-blocker therapy in contrast to seven deaths among those in whom beta-blocker therapy was deferred. These findings for a secondary end point in a subgroup were not considered sufficient to warrant a recommendation regarding clinical use. There was a lower incidence of reinfarction (2.7% versus 5.1%, p = 0.02) and recurrent chest pain (18.8% versus 24.1%, p less than 0.02) at 6 days in the immediate intravenous group. Thus, in appropriate postinfarction patients, beta-blockers are safe when given early after thrombolytic therapy and are associated with decreased myocardial ischemia and reinfarction in the first week but offer no benefit over late administration in improving ventricular function or reducing mortality.     

Intracerebral hemorrhage, cerebral infarction, and subdural hematoma after acute myocardial infarction and thrombolytic therapy in the Thrombolysis in Myocardial Infarction Study. Thrombolysis in Myocardial Infarction, Phase II, pilot and clinical trial

In the Thrombolysis in Myocardial Infarction, Phase II pilot and clinical trial, 908 patients [326 (35.9%) in the pilot study and 582 (64.0%) in the randomized study] were treated with 150 mg recombinant tissue-type plasminogen (rt-PA) activator in combination with heparin and aspirin, and 3,016 patients [64 (2.1%) in the pilot study and 2,952 (97.9%) in the randomized study] were treated with 100 mg rt-PA in combination with heparin and aspirin. Adverse neurological events occurred in 23 patients treated with 150 mg rt-PA (2.5%) [nine cerebral infarctions (1.0%), 12 intracerebral hemorrhages (1.3%), and two subdural hematomas (0.2%)] and in 33 patients treated with 100 mg rt-PA (1.1%) [20 cerebral infarctions (0.7%), 11 intracerebral hemorrhages (0.4%), and two subdural hematomas (0.1%)]. The difference in adverse neurological events observed comparing the two rt-PA regimens was primarily due to a higher frequency of intracerebral bleeding among patients treated with 150 mg rt-PA (1.3% versus 0.4%, p less than 0.01). Patients with recent (within 6 months) histories of stroke were not eligible for the study, and patients with any history of cerebrovascular disease were declared ineligible early in the study. The small number of patients (89, or 2.3%) with any history of neurological disease, intermittent cerebral ischemic attacks, or stroke who were enrolled before the stricter eligibility criteria were imposed or on the basis of incomplete baseline information experienced an increased frequency of intracerebral hemorrhage compared with patients without such histories (3.4% versus 0.5%). Mortality at 6 weeks after presentation among 23 patients who had intracerebral hemorrhage was 47.8%. Intracerebral hemorrhage is a severe but infrequent complication of rt-PA therapy for acute myocardial infarction. The combined frequency of intracerebral hemorrhage, subdural hematoma, and cerebral infarction after treatment with 100 mg rt-PA is comparable to that observed in other trials with thrombolytic agents in acute myocardial infarction.     

Consequences of reocclusion after successful reperfusion therapy in acute myocardial infarction. TAMI Study Group

To determine the clinical consequences of reocclusion of an infarct-related artery after reperfusion therapy, we evaluated 810 patients with acute myocardial infarction. Patients were admitted into four sequential studies with similar entry criteria in which patency of the infarct-related artery was assessed by coronary arteriography 90 minutes after onset of thrombolytic therapy. Successful reperfusion was established acutely in 733 patients. Thrombolytic therapy included tissue-type plasminogen activator (t-PA) in 517, urokinase in 87, and a combination of t-PA and urokinase in 129 patients. All patients received aspirin, intravenous heparin and nitroglycerin, and diltiazem during the recovery phase. A repeat coronary arteriogram was performed in 88% of patients at a median of 7 days after the onset of symptoms. Reocclusion of the infarct-related artery occurred in 91 patients (12.4%), and 58% of these were symptomatic. Angiographic characteristics at 90 minutes after thrombolytic therapy that were associated with reocclusion compared with sustained coronary artery patency were right coronary infarct-related artery (65% versus 44%, respectively) and Thrombolysis in Myocardial Infarction (TIMI) flow 0 or 1 (21% versus 10%, respectively) before further intervention. Median (interquartile value) degree of stenosis in the infarct-related artery at 90 minutes was similar between groups: 99% for reoccluded (value, 90/100%) compared with 95% for patent (value, 80/99%). Patients with reocclusion had similar left ventricular ejection fractions compared with patients with sustained patency at follow-up. However, patients with reocclusion at follow-up had worse infarct-zone function at -2.7 (value, -3.2/-1.8) versus -2.4 (SD/chord) (value, -3.1/-1.3) (p = 0.016). The recovery of both global and infarct-zone function was impaired by reocclusion of the infarct-related artery compared with maintained patency; median delta ejection fraction was -2 compared with 1 (p = 0.006) and median delta infarct-zone wall motion was -0.10 compared with 0.34 SD/chord (p = 0.011), respectively. In addition, patients with reocclusion had more complicated hospital courses and higher in-hospital mortality rates (11.0% versus 4.5%, respectively; p = 0.01). We conclude that reocclusion of the infarct-related artery after successful reperfusion is associated with substantial morbidity and mortality rates. Reocclusion is also detrimental to the functional recovery of both global and infarct-zone regional left ventricular function. Thus, new strategies in the postinfarction period need to be developed to prevent reocclusion of the infarct-related artery.     

Modifiers of timing and possible triggers of acute myocardial infarction in the Thrombolysis in Myocardial Infarction Phase II (TIMI II) Study Group.

OBJECTIVES. The aim of this study was to provide insight into the mechanism of acute myocardial infarction by determining the modifiers of timing and possible triggers of onset of infarction. BACKGROUND. A higher frequency of onset of acute myocardial infarction has been reported in the morning with a peak in the 1st 3 h after awakening. This observation suggests that the onset of infarction may be triggered by activity in the morning and at other times of the day. METHODS. The clinical history of the 3,339 patients entered into the Thrombolysis in Myocardial Infarction phase II study was analyzed to determine characteristics predicting a higher frequency of infarction between 6 AM and noon, and onset of infarction during exertion. RESULTS. A higher proportion (34.4%) of infarctions began in the morning (6 AM to noon) compared with other times of the day. Characteristics independently predicting a higher frequency between 6 AM to noon were no beta-adrenergic blocking agent use in the 24 h before infarction, no discomfort other than the index pain in the preceding 48 h, occurrence of the infarction on a weekday and no history of current smoking. In 18.7% of patients, infarction occurred during moderate or marked physical activity. Independent predictors of exertion-related infarction included male gender, no history of current smoking, white race, no use of calcium channel blocking agents or nitrates in the preceding 24 h, the absence of either chest pain at rest in the 3 weeks before infarction or any pain in the preceding 48 h, the absence of new onset angina and the presence of exertional pain in the preceding 3 weeks. Compared with patients whose infarction occurred at rest or during mild activity, those with exertion-related infarction had fewer coronary vessels with > or = 60% stenosis (p = 0.002) and were more likely to have an occluded infarct-related vessel after thrombolytic therapy (p = 0.01). CONCLUSIONS. Further study of the timing and activity at onset of infarction may provide insight into the pathophysiologic mechanisms causing acute myocardial infarction and provide clues to preventive measures.     

Complete atrioventricular block complicating inferior wall acute myocardial infarction treated with reperfusion therapy. TAMI Study Group

Previous studies report larger myocardial infarcts and increased in-hospital mortality rates in patients with inferior wall acute myocardial infarction (AMI) and complete atrioventricular block (AV), but the clinical implications of these complications in patients treated with reperfusion therapy have not been addressed. The clinical course of 373 patients--50 (13%) of whom developed complete AV block--admitted with inferior wall AMI and given thrombolytic therapy within 6 hours of symptom onset was studied. Acute patency rates of the infarct artery after thrombolytic therapy were similar in patients with or without AV block. Ventricular function measured at baseline and before discharge in patients with complete AV block showed a decrement in median ejection fraction (-3.5 vs -0.4%, p = 0.03) and in median regional wall motion (-0.14 vs +0.24 standard deviations/chord, p = 0.05). The reocclusion rate was higher in patients with complete AV block (29 vs 16%, p = 0.03). Patients with complete AV block had more episodes of ventricular fibrillation or tachycardia (36 vs 14%, p less than 0.001), sustained hypotension (36 vs 10%, p less than 0.001), pulmonary edema (12 vs 4%, p = 0.02) and a higher in-hospital mortality rate (20 vs 4%, p less than 0.001), although the mortality rate after hospital discharge was identical (2%) in the 2 groups. Multivariable logistic regression analysis revealed that complete AV block was a strong independent predictor of in-hospital mortality (p = 0.0006). Thus, despite initial successful reperfusion, patients with inferior wall AMI and complete AV block have higher rates of in-hospital complications and mortality.     

Degree of residual stenosis in the culprit coronary artery after thrombolytic administration (Thrombolysis In Myocardial Infarction [TIMI] trials)

This study was undertaken to characterize residual stenosis after thrombolytic administration and to evaluate clinical and angiographic features and early outcomes of patients with mild residual obstruction after thrombolytic administration. Patients who underwent angiography at 90 minutes after thrombolytic administration in the Thrombolysis In Myocardial Infarction 4, 10A, 10B, and 14 trials were divided into 3 groups according to the degree of residual stenosis measured by quantitative coronary angiography: patients with a patent culprit artery with <50% stenosis, patients with patent arteries and residual stenosis ≥50%, and patients with occluded arteries. Only 8.9% of the patients (188 of 2,119) had an infarct-related artery luminal diameter stenosis of <50% 90 minutes after thrombolysis. Compared with patients with patent arteries and ≥50% stenosis, patients with mild residual obstruction were younger (56.8 vs 58.6 years; p = 0.03), had fewer prior myocardial infarctions (6.9% vs 13.3%; p = 0.01), fewer eccentric (19.8% vs 42.1%; p <0.0001), ulcerated (7.5% vs 13.2%; p = 0.03), and collateralized (6.6% vs 13.2%, p = 0.01) lesions, but a greater thrombus burden (29.7% vs 18.3%, p = 0.0002). Among patients with patent arteries, a residual stenosis of <50% was associated with a significantly lower composite of in-hospital death, myocardial infarction, and congestive heart failure (2.8% vs 7.1%, p = 0.03). Thus, a minority of patients have a mild residual obstruction at 90 minutes after thrombolytic administration. These patients have less complex lesions with greater thrombus burdens and better clinical outcomes.     

Differences in patients with acute myocardial infarction treated with primary angioplasty or thrombolytic therapy. Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) Study Group

BACKGROUND: Little is known about the differences in patients with acute myocardial infarction (AMI) treated with primary angioplasty or intravenous thrombolysis in clinical practice. METHODS: In all, 5,906 patients with AMI were registered by the Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) study. Of these, 491 (8.3%) patients were treated with primary angioplasty and 2,817 (47.7%) with intravenous thrombolysis. RESULTS: There were only minor differences in baseline characteristics between the two groups. Prehospital delay time (median) was longer in the angioplasty group than in the thrombolysis group (161 vs. 120, p = 0.001), as was door-to-treatment time (88 vs. 30 min; p = 0.001). Patients treated with primary angioplasty more often had contraindications for thrombolytic therapy (12.9 vs. 6%, p = 0.001) and received beta blockers (65 vs. 58.1%, p = 0.004), heparin (98.2 vs. 91.6%, p = 0.001), angiotensin-converting enzyme (ACE) inhibitors (64.8 vs. 50%, p = 0.001) and "optimal" concomitant medication (56.4 vs. 42.9%, p = 0.001) more often. Univariate analysis showed a significant lower incidence of heart failure (5.3 vs. 16.5%, p = 0.001), postinfarct angina (7.3 vs. 16.4%, p = 0.001), in-hospital death (7.9 vs. 11.7%, p = 0.015) and the combined end point (21.6 vs. 40.3%, p = 0.001) in these patients. Stepwise logistic regression analysis revealed optimal concomitant medication [odds ratio (OR) = 0.94, 95% confidence interval (CI): 0.89-0.98) and the type of revascularization (OR = 0.65, 95% CI: 0.58-0.73) to be associated with a significant reduction in the incidence of the combined end point. Similar results were obtained in all predefined subgroups. CONCLUSIONS: In clinical practice, patients treated with primary angioplasty are more often treated with beta blockers and ACE inhibitors than patients treated with intravenous thrombolysis. Thus, the selection of patients and the type of revascularization contributes to the reduction in mortality, overt heart failure, and postinfarct angina in these patients.     

Brachial approach to emergency cardiac catheterization during thrombolytic therapy for acute myocardial infarction. TAMI Study Group

The use of the brachial approach to acute coronary intervention has not been previously studied. In the course of the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) trials, we used the transbrachial approach to cardiac catheterization with or without angioplasty in 202 of 704 (28.6%) patients. The baseline characteristics of age, sex, risk factors, medical history, time from symptom onset to therapy, and left ventricular function were similar for the 2 different approaches. Time from therapy to coronary angiography was not delayed by the brachial approach compared with the femoral approach: 97.1 +/- 26 min vs. 99.9 +/- 133.8 min, respectively. Chemical patency was established in 78 vs. 73% of patients and technical success with acute PTCA with the brachial approach was 89% vs. 78% with the femoral approach. Clinical outcomes were quite similar with respect to death (6 vs. 6%), reocclusion (10 vs. 14%), and emergency coronary bypass surgery (5 vs. 6%). Baseline hematocrit was 43.9 +/- 4.4 and 43.5 +/- 4.8, respectively with a nadir of 32.9 +/- 5.6 vs. 33.0 +/- 5.4. The need for vascular repair occurred in 1% vs. 3% of patients and retroperitoneal hemorrhage was documented in 1% vs. 1% of patients. This study indicates that in the hands of experienced operators the transbrachial approach to acute coronary intervention in the acute phase of treatment with thrombolytic therapy can be used with equal risks and efficacy as the femoral approach.     

Relation of temporal creatine kinase-MB release and outcome after thrombolytic therapy for acute myocardial infarction. TAMI Study Group

Measuring biochemical marker release after acute myocardial infarction helps in estimating infarct size and prognosis. We sought to relate in-hospital outcomes and curve-fitted creatine kinase (CK)-MB variables after thrombolysis. We measured CK-MB mass initially and at 30 and 90 minutes, and at 3, 8, and 20 hours after thrombolysis in 130 patients also undergoing cardiac catheterization at 90 minutes and at 5 to 7 days. Data were fitted, and maximums and curve areas calculated. CK-MB maximums related to infarct location (p = 0.014) and time to therapy (p = 0.002); curve area did not. Neither maximums nor curve area related to Thrombolysis in Myocardial Infarction trial flow grade at 90 minutes. Maximums related to ejection fraction at 90 minutes (p = 0.0004) and at 5 to 7 days (p = 0.0014), as did curve area (p = 0.0076 and 0.030, respectively). Maximums related to infarct zone function at 90 minutes (p = 0.024) and at 5 to 7 days (p = 0.042); curve area related only at 90 minutes (p = 0.027). Both maximums and curve area predicted congestive heart failure (p = 0.008 and p = 0.042, respectively) and a composite of congestive heart failure or death (p = 0.004 and p = 0.047, respectively); however, after adjusting for maximums, curve area no longer predicted congestive heart failure (p = 0.92). Maximums predicted the composite outcome after adjustment for curve area, and showed a trend toward predicting congestive heart failure (p = 0.089). We conclude that CK-MB maximums relate to infarct zone function, left ventricular function, and in-hospital outcomes after thrombolysis for acute myocardial infarction.