Author + information
- Received February 2, 1996
- Revision received April 26, 1996
- Accepted May 13, 1996
- Published online October 1, 1996.
- TATSUJI KONO*
- ↵*Address for correspondence: Dr. Tatsuji Kono, Osaka Mishima Critical Care Medical Center, 11-1 Minami Akutagawa-cho, Takatsuki-City, Osaka 569, Japan.
- HIROSHI MORITA,
- TAKUYA NISHINA and
- MASASHI FUJITA
- AKIRA FUJIWARAb
Objectives. Using a prospective, randomized design, we tested our hypothesis that the augmentation of diastolic pressure by intraaortic balloon counterpulsation (IABP) would improve the late patency of the occluded coronary artery in patients with early failure of thrombolytic therapy.
Background. Rescue angioplasty is often performed in patients in whom thrombolysis has failed, although 30% to 60% of the infarct-related arteries that are closed early after thrombolytic therapy will open later with conservative therapy.
Methods. The study included 45 patients in whom thrombolysis had failed, despite treatment with intravenous tissue-type plasminogen activator (alteplase 0.75 mg/kg body weight) delivered over 60 min within 12 h of the onset of symptoms. All patients underwent coronary angiography 60 min after initiation of thrombolytic therapy (baseline), and Thrombolysis in Myocardial Infarction (TIMI) grade 0, 1 or 2 flow was defined as failed thrombolysis. The patients were randomized to groups receiving IABP for 48 h (n = 23) or conservative therapy (n = 22, control subjects) at the end of cardiac catheterization. The late patency of the infarct-related artery, the primary end point of the study, was evaluated 3 weeks after myocardial infarction. Stenosis of the infarct-related artery was measured using a computer-assisted quantitative angiographic system in blinded manner. Data are expressed as mean value ± SEM.
Results. There was no difference with regard to the baseline value for TIMI flow grade between the groups. However, 3 weeks after myocardial infarction, the patients treated with IABP had a significantly higher frequency of TIMI flow grade 3, lower residual percent stenosis and larger minimal lumen diameter of the infarct-related artery than did the control subjects (74% vs. 32%, p < 0.05; 42 ± 5% vs. 68 ± 6%, p < 0.01; and 1.6 ± 0.1 vs. 0.9 ± 0.2 mm, p < 0.01, respectively).
Conclusions. These findings suggest that in patients with early failure of thrombolytic therapy, IABP may improve late patency of the occluded coronary artery, probably due to augmented perfusion pressure.
The beneficial effects of reperfusion with thrombolytic therapy are now well established in patients with acute myocardial infarction; nevertheless, the infarct-related artery remains occluded in at least 25% of patients treated with thrombolysis [1–5]. In the patients in whom thrombolytic therapy has failed to restore anterograde coronary blood flow, rescue angioplasty is frequently used to establish the patency of the infarct artery [6–9]. However, the clinical benefit of this therapy remains unclear because of the high reocclusion rate and the high mortality rate when it fails [6–9]. It is also known that 30% to 60% of the infarct arteries that are closed early after thrombolytic therapy will open within the time window in which clinical benefit may still exist and that the residual stenosis may improve later (the so-called catch-up phenomenon) [10, 11]. Such late reperfusion, may improve survival without the risk involved with invasive procedures coupled with thrombolytic therapy. It is reported that reperfusion with tissue-type plasminogen activator (t-PA) may be blood pressure dependent and that arterial diastolic pressure augmentation by intraaortic balloon counterpulsation (IABP) enhances thrombolysis, leading to faster reperfusion [12–14]. Using a prospective, randomized study design, we tested our hypothesis that the augmentation of diastolic pressure by IABP would improve the late patency of the occluded coronary artery in patients with early failure of thrombolytic therapy.
Study patients. The patient group consisted of 45 patients with acute myocardial infarction in whom thrombolysis had failed. Of 296 patients with acute myocardial infarction admitted to the Osaka Mishima Critical Care Medical Center between December 1992 and October 1995, 94 received intravenous t-PA within 12 h of the onset of symptoms. In each of them, the patency of the infarct-related artery was evaluated by coronary angiography 60 min after the initiation of intravenous t-PA. Forty-five (47.9%) of these 94 patients showed persistent occlusion or partial reperfusion (Thrombolysis in Myocardial Infarction [TIMI] flow grade 0, 1 or 2), and in these patients thrombolysis failed [15–18]; 23 of them were treated with IABP for 48 h, and the other 22 patients, who served as control subjects, received conservative therapy according to the study protocol. Rescue angioplasty was not performed in any of the patients in this study. Acute myocardial infarction was diagnosed by the presence of chest pain suggestive of myocardial ischemia lasting >30 min and at least 0.1 mV of ST segment elevation in at least two contiguous leads despite treatment with nitrates. The diagnosis was confirmed by the documentation of elevation of cardiac enzymes. The exclusion criteria of this protocol were cardiogenic shock (systolic blood pressure <80 mm Hg unresponsive to fluids and vasopressors), uncontrolled hypertension (>180/110 mm Hg), prior cerebrovascular accident, evidence of recent or active bleeding or a history of myocardial infarction. Patients with peripheral vascular disease (defined as diminished femoral pulses and absent pedal pulses) were also excluded from this study.
Study protocol. After written informed consent was obtained, patients with acute myocardial infarction who were found to satisfy the eligibility criteria received intravenous t-PA (alteplase), at a total dose of 0.75 mg/kg body weight, over 60 min with 10% given as a bolus. The patients were transferred to the cardiac catheterization laboratory, where coronary angiography was performed to evaluate the infarct-related artery. Arterial access was obtained through the femoral route, and heparin (5,000 U) was administered immediately after access was established. The patency of the infarct artery was evaluated 60 min after the initiation of intravenous t-PA. The flow pattern of the infarct artery was graded according to the TIMI classification [19, 20], and TIMI grade 0, 1 or 2 flow was defined as failed thrombolysis [15–18]. Patients were randomized to the IABP or conservative therapy group at the end of cardiac catheterization using a predetermined randomization list along with sealed envelopes. In the patients assigned to IABP group, the pump (9.5F) was inserted percutaneously through the same femoral artery through which the cardiac catheterization was performed. Intraaortic balloon counterpulsation was continued for 48 h at a rate of 1:1, and the patients were gradually weaned from the pump over the last 12 h before removal. Intraaortic balloon counterpulsation was stopped earlier in the event of a complication such as limb ischemia or hemorrhage at the access site. Adjunct therapy included daily aspirin (81 mg) and intravenous heparin (begun with a 5,000-U bolus during cardiac catheterization and maintained with an infusion of 1,000 U/h), adjusted as required to keep the activated partial thromboplastin time (aPTT) at approximately twice the upper limit of normal for at least 72 h. Other medications such as nitrates, beta-adrenergic blocking agents, angiotensin-converting enzyme inhibitors, analgesic agents and antiarrhythmic agents were administered at the discretion of the attending physician. The late patency of the infarct artery, the primary end point of the study and the global left ventricular function were evaluated in all patients in whom thrombolysis had failed 3 weeks after myocardial infarction. Clinical morbidity and mortality were assessed during 30-day follow-up periods. The stenosis of the infarct artery was measured with a computer-assisted quantitative angiographic system (Heart Database System, Baxter, Tokyo) , and left ventricular end-diastolic volume, left ventricular end-systolic volume and left ventricular ejection fraction were measured using left ventriculography (single plane in right anterior oblique projection) with an area-length method . The segmental wall motion of the left ventricle was quantitated using the centerline method . All cineangiograms were evaluated by a single experienced cardiologist who had no knowledge of the patients' characteristics. The protocol of the study was approved by the Institutional Review Board of the Osaka Mishima Critical Care Medical Center, and written informed consent was obtained from all patients or their family members after the purpose of the treatment was fully explained.
Cardiac enzyme measurements. Serum creatine kinase (CK) and its cardiac isoenzyme (CK-MB) were measured at admission and every 4 h after admission for 24 h. The values for peak enzyme activity and time to peak activity were determined for individual patients. The normal range of CK in our hospital is 21 to 232 U/liter, and that of CK-MB is 0 to 10 U/liter.
Evaluation of clinical outcomes. Recurrent ischemia was defined as symptoms compatible with myocardial ischemia lasting >20 min associated with new ST segment or T wave changes on the electrocardiogram. Cardiac enzymes were obtained whenever a clinical event occurred, suggesting severe recurrent ischemia, and reinfarction was diagnosed when a second elevation in cardiac enzymes occurred. Congestive heart failure was recorded when one or more of the following events were documented: pulmonary edema depicted on the chest radiograph, rales more extensive than bibasilar or requirement for inotropic support.
Statistical analysis. Comparisons between the patients treated with IABP and the control subjects were made using the unpaired Student t test to compare continuous variables and the chi-square test to compare nominal data. All tests of significance were two-tailed, and p < 0.05 was considered significant. Data are expressed as mean value ± SEM.
The basic characteristics of the patients treated with IABP were well matched to those of the control subjects (Table 1). There were no differences between the two groups with regard to age, gender, time from onset of symptoms to initiation of thrombolysis, infarct-related artery, incidence of multivessel disease, presence of collateral channels or coronary risk factors. Intraaortic balloon counterpulsation was terminated within 24 h in one patient (4.2%) because of hemorrhagic complications at the puncture site. There was no difference with regard to the baseline values for TIMI flow grade between the groups, as shown in Fig. 1. However, 3 weeks after myocardial infarction, the patients treated with IABP had a significantly higher frequency of TIMI grade 3 flow, lower residual percent stenosis and larger minimal lumen diameter of the infarct artery compared with control subjects (74% vs. 32%, p < 0.05; 42 ± 5% vs. 68 ± 6%, p < 0.01; and 1.6 ± 0.1 vs. 0.9 ± 0.2 mm, p < 0.01, respectively). The left ventricular end-diastolic volume index, left ventricular end-systolic volume index and left ventricular ejection fraction were not different in the two patient groups at 3 weeks after myocardial infarction (Table 2). However, the left ventricular end-diastolic pressure was significantly lower in patients treated with IABP than in control subjects. The regional wall motion of the infarct segment at this time was not different in the two groups with the occlusion of either the left anterior descending coronary artery or the right coronary artery/left circumflex artery (Table 2). The peak CK was not different in the two groups, but the time to peak CK in patients treated with IABP was significantly shorter than that in control subjects (Table 3). There were no differences between the two groups with regard to the incidence of recurrent ischemia, ventricular tachycardia or ventricular fibrillation, or both, or death; performance of coronary artery bypass grafting; or incidence of stroke during 30-day follow-up periods (Table 3), although congestive heart failure and coronary angioplasty tended to be less frequent in the patients treated with IABP. The two groups showed similar incidences of major hemorrhagic complications, with similar incidences of blood transfusions and numbers of units transfused (Table 4). Vascular access hemorrhage accounted for all cases of hemorrhagic complications. No patient in the study had aortic dissection or retroperitoneal hemorrhage or required amputation of part of a limb. There were few vascular complications overall, with statistically insignificant differences between the two groups.
Among the patients with early failure of thrombolytic therapy, those treated with IABP showed greater patency of the infarct-related artery with milder residual stenosis than did the control subjects at 3 weeks after myocardial infarction. This finding suggests that IABP, may improve the late patency of the occluded coronary artery in patients with early failure of thrombolytic therapy probably due to augmented perfusion pressure.
Patency of the infarct-related artery. Studies of the pathophysiology of acute myocardial infarction have demonstrated that a thrombus over a ruptured atheroma is a principal mechanism of acute myocardial infarction . Reperfusion within 1.5 h may allow for marked recovery of left ventricular function ; however, reperfusion after 6 h does not generally result in marked recovery of systolic function [1–5]. Nevertheless, a paradoxical relation between improved in-hospital survival and lack of improvement in left ventricular function has been noted, and the patency of the infarct-related artery has been suggested to be a major determinant of early and late survival [25–27]. An increasing number of studies suggest that achieving infarct artery patency may favorably influence left ventricular remodeling and life-threatening arrhythmias, even when patency is established at a time when salvage of ischemic myocardium is unlikely [28–33]. Furthermore, infarct artery patency may become important as a source of collateral vessels when the contralateral coronary artery becomes jeopardized [30, 31].
Role of rescue angioplasty. Early infarct-related artery patency is established in 50% to 85% of patients with thrombolytic therapy, depending on the agent that is used to achieve thrombolysis [1–5]. Thrombolysis in Myocardial Infarction trial flow grades 0 and 1 have been designated as perfusion failure, and flow grades 2 and 3 have traditionally been viewed as indicative of reperfusion success. However, recent investigators have proved that patients with TIMI flow grade 3 showed significantly better outcomes than did those with lower grades of flow [14–17]. Therefore, TIMI grade 0, 1 or 2 flow was defined as failed thrombolysis in the present study. In the patients in whom thrombolytic therapy had failed to restore anterograde coronary flow, rescue angioplasty is frequently used to establish infarct artery patency. It is reported that rescue angioplasty appears to be useful in the prevention of death or severe heart failure, with improvement of exercise . However, the clinical benefit of rescue angioplasty remains unclear. First, rescue angioplasty requires a very experienced physician, who may not always be available on a 24-h basis. Second, rescue angioplasty is ineffective in reestablishing anterograde coronary blood flow in 10% to 15% of patients, and reocclusion occurs in 15% to 20% of the remaining patients, depending on the thrombolytic agent used [5, 6]. Third, the left ventricular ejection fraction is seldom improved . Finally, it is known that 30% to 60% of the infarct arteries that are closed early after thrombolytic therapy will open within the time window within which clinical benefit may still exist, and that the residual stenosis may improve later (the so-called catch-up phenomenon) [9, 10]. Such late reperfusion may improve survival without the risk associated with the invasive procedures coupled with thrombolytic therapy.
Role of intraaortic balloon counterpulsation. Several studies have demonstrated an important relation between hemodynamic variables and successful thrombolysis, suggesting that reperfusion with thrombolytic therapy may be blood pressure dependent [11–13]. In the present study, the infarct-related artery showed greater patency (complete reperfusion) and the residual stenosis was less severe in the patients treated with IABP than in the control subjects at 3 weeks after myocardial infarction. It has been noted by several investigators that CK and CK-MB peaks are not useful in distinguishing among groups of patients by TIMI perfusion grade, but the time to peak shortens progressively for both CK and CK-MB with increasing perfusion grade . In the present study, the time to peak CK was significantly shorter in the patients treated with IABP than in the control subjects, suggesting enhanced reperfusion by IABP, although we did not perform coronary angiography soon after the initiation of IABP. The effects of IABP on coronary blood flow are controversial , but it was reported that in a canine model of acute myocardial infarction, augmentation of diastolic arterial pressure by IABP enhances thrombolysis, leading to faster reperfusion [12, 13]. Several mechanisms whereby arterial blood pressure affects reperfusion with thrombolytic therapy have been speculated [12, 13]. First, the arterial diastolic pressure, being the coronary perfusion pressure, directly affects coronary blood flow and the delivery of the thrombolytic agents to a partially occlusive thrombus. Second, depending on its magnitude, the arterial pressure may exert a mechanically disruptive effect on the thrombus by creating defects in the thrombus. Finally, the pressure wave could possibly separate the obstructive thrombus from the vessel wall by vessel distention and facilitate the ingress of the thrombolytic agent. These latter two mechanisms could increase the surface area of the thrombus available for thrombolytic agent binding and potentially facilitate thrombolysis and reperfusion. In the canine model of acute myocardial infarction, Gurbel et al.  and Prewitt et al.  demonstrated that enhancement of reperfusion by IABP was not related to an increase in coronary blood flow but was considered to be due to an effect of the augmented diastolic blood pressure wave on the obstructing thrombus. It has also been reported that IABP may improve sustained coronary artery patency and improve overall clinical outcomes such as in-hospital mortality, recurrent ischemia and requirement for emergency revascularization with coronary angioplasty or bypass surgery in patients with acute myocardial infarction . In the present study, the left ventricular ejection fraction and regional wall motion of the infarct segment at 3 weeks after myocardial infarction in the patients treated with IABP were not different from those in the control subjects, but the left ventricular end-diastolic pressure at this time was significantly lower and the incidence of congestive heart failure was slightly lower. Although the use of IABP in patients undergoing emergency cardiac catheterization during acute myocardial infarction has been associated with both an increase in hemorrhagic complications and a higher rate of vascular complications [37, 38], we found similar incidences of major hemorrhagic complications in the two groups, with similar incidences of blood transfusions and number of units transfused and few vascular complications overall, with statistically insignificant differences. The present study demonstrates the relative benefit-risk ratio of a reperfusion strategy with IABP compared with conservative treatment to facilitate and sustain the patency of the infarct artery. The benefits of IABP were not offset by higher rates of vascular and hemorrhagic complications.
Study limitations. The relative improvement of patency of the infarct-related artery in patients treated with IABP might have been less impressive if a standard front-loaded regimen had been used. The degree of aPTT prolongation could affect late patency of the infarct artery; however, we did not measure aPTT at a fixed time interval, so we could not argue this issue in the present study. Because we did not perform coronary angiography shortly after randomization, the exact time of reperfusion with IABP was not clearly determined in our study. The failure to show a difference in regional wall motion, left ventricular ejection fraction, CK enzyme release or complication rates could be due to the fact that reperfusion was achieved late in these patients. A larger study would be required to disclose the potential beneficial effect of infarct artery patency independent of improvement in left ventricular function and to disclose the relative benefit-risk ratio of a reperfusion strategy with IABP. We could not compare the IABP treatment strategy with that of rescue angioplasty because they are radically different strategies.
Conclusions. These findings suggest that careful use of IABP can be one method of improving the late patency of the occluded coronary artery in patients with early failure of thrombolytic therapy.
A.1 Abbreviations and Acronyms
aPTT = activated partial thromboplastin time
CK = creatine kinase
CK-MB = creatine kinase, MB fraction
IABP = intraaortic balloon counterpulsation
TIMI = Thrombolysis in Myocardial Infarction
t-PA = tissue-type plasminogen activator
↵1 This study was supported in part by a research grant from Osaka Mishima Critical Care Medical Center, Osaka, Japan.
- Received February 2, 1996.
- Revision received April 26, 1996.
- Accepted May 13, 1996.
- THE AMERICAN COLLEGE OF CARDIOLOGY
- ↵Stampfer MJ, Goldhaber SZ, Yusuf S, Peto R, Hennekens CH. Effect of intravenous streptokinase on acute myocardial infarction: pooled results from randomized trials. N Engl J Med 1982;307:1180–2.
- Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI). Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986;1:397–402.
- Second International Study of Infarct Survival Collaborative Group. Randomized trial of intravenous streptokinase, oral aspirin, both or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988;2:349–60.
- Norris RM
- ↵Koren G, Weiss AT, Hasin Y, et al. Prevention of myocardial damage in acute myocardial ischemia by early treatment with intravenous streptokinase. N Engl J Med 1985;313:1384–9.
- ↵Califf RM, Topol EJ, Stack RS, et al., for the TAMI Study Group. Evaluation of combination thrombolytic therapy and timing of cardiac catheterization in acute myocardial infarction. Results of Thrombolysis and Angioplasty in Myocardial Infarction-Phase 5 Randomized Trial. Circulation 1991;83:1543–56.
- Califf RM, Topol EJ, George BS, et al. for the TAMI Study Group. 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. Circulation 1988;77:1090–9.
- ↵Abbottsmith CW, Topol EJ, George BS, et al. Fate of patients with acute myocardial infarction with patency of the infarct-related vessel achieved with successful thrombolysis versus rescue angioplasty. J Am Coll Cardiol 1990;16:770–8.
- ↵PRIMI Trial Study Group. Randomized double-blind trial of recombinant prourokinase against streptokinase in acute myocardial infarction. Lancet 1989;1:863–7.
- ↵Neuhaus KL, von Essen R, Tebbe U, et al. Improved thrombolysis in acute myocardial infarction with front-loaded administration of alteplase: results of the rt-PA APSAC patency study (TAPS). J Am Coll Cardiol 1992;19:885–91.
- ↵Bates ER, Topol EJ. Limitations of thrombolytic therapy for acute myocardial infarction complicated by congestive heart failure and cardiogenic shock. J Am Coll Cardiol 1991;18:1077–84.
- ↵Gurbel PA, Anderson D, MacCord CS, et al. Arterial diastolic pressure augmentation by intra-aortic balloon counterpulsation enhances the onset of coronary artery reperfusion by thrombolytic therapy. Circulation 1994;89:361–5.
- ↵Prewitt RM, Gu S, Schick U, Ducas J. Intraaortic balloon counterpulsation enhances coronary thrombolysis induced by intravenous administration of a thrombolytic agent. J Am Coll Cardiol 1994;23:794–8.
- ↵Vogt A, von Essen R, Tebbe U, Feuerer W, Appel K-F, Neuhaus KL. Impact of early perfusion status of the infarct-related artery on short-term mortality after thrombolysis for acute myocardial infarction: retrospective analysis of four German multicenter studies. J Am Coll Cardiol 1993;21:1391–5.
- The GUSTO Investigators. An international randomized trial comparing thrombolytic strategies for acute myocardial infarction. N Engl J Med 1993;329:673–82.
- TEAM-2 Investigators,
- Karagounis L,
- Sorensen SG,
- Menlove RL,
- Moreno F,
- Anderson JL
- Anderson JL, Karagounis LA, Becker LC, Sorensen SG, Menlove RL, for the TEAM-3 Investigators. TIMI perfusion grade 3 but not grade 2 results in improved outcome after thrombolysis for myocardial infarction. Ventriculographic, enzymatic, and electrocardiographic evidence from the TEAM-3 study. Circulation 1993;87:1829–39.
- ↵The TIMI Study Group. The thrombolysis in myocardial infarction (TIMI) trial. N Engl J Med 1985;312:932–6.
- Cheseboro JH, Knatterud G, Roberts R, et al. Thrombolysis in Myocardial Infarction (TIMI) trial, phase I: a comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Circulation 1987;76:142–54.
- ↵Onaka H, Hirota Y, Kita Y, et al. The effect of pravastatin on prevention of restenosis after successful percutaneous transluminal coronary angioplasty. Jpn Circ J 1994;58:100–6.
- Sheehan FH,
- Bolson EL,
- Dodge HT,
- Mathey DG,
- Schofer J,
- Woo HW
- ↵Davies MJ, Thomas AC. Plaque fissuring: the cause of acute myocardial infarction, sudden ischaemic death, and crescendo angina. Br Heart J 1985;53:363–73.
- ↵Kennedy JW, Ritchie JL, Davis KB, Fritz JK. Western Washington randomized trial of intracoronary streptokinase in acute myocardial infarction. N Engl J Med 1983;309:1477–82.
- Kennedy JW, Ritchie JL, Davis KB, Stadius ML, Maynard C, Fritz JK. The Western Washington randomized trial of intracoronary streptokinase in acute myocardial infarction: a 12-month follow-up report. N Engl J Med 1985;312:1073–8.
- Stadius ML, Davis K, Maynard C, Ritchie JL, Kennedy JW. Risk stratification for one-year survival based on characteristics identified in the early hours of acute myocardial infarction: the Western Washington intracoronary streptokinase trial. Circulation 1986;74:703–11.
- ↵Jeremy RW, Hackworthy RA, Bautovich G, Hutton BF, Harris PJ. Infarct artery perfusion and changes in left ventricular volume in the month after acute myocardial infarction. J Am Coll Cardiol 1987;9:989–95.
- Kersschot IE, Brugada P, Ramentol M, et al. Effects of early reperfusion in acute myocardial infarction on arrhythmias induced by programmed stimulation: a prospective, randomized study. J Am Coll Cardiol 1986;7:1234–42.
- ↵Braunwald E. Myocardial reperfusion, limitation of infarct size, reduction of left ventricular dysfunction, and improved survival. Should the paradigm be expanded? Circulation 1989;79:441–4.
- Califf RM, Topol EJ, Gersh BJ. From myocardial salvage to patient salvage in acute myocardial infarction: the role of reperfusion therapy. J Am Coll Cardiol 1989;14:1382–8.
- Gang ES, Lew AS, Hong M, Wang FZ, Liebert CA, Peter T. Decreased incidence of ventricular late potential after successful thrombolysis for acute myocardial infarction. N Engl J Med 1989;321:712–6.
- Anderson JL. Thrombolysis for acute myocardial infarction: making sense of the clinical trials data. J Intervent Cardiol 1992;5:127–36.
- ↵Ellis SG, da Silva ER, Heyndrickx G, et al., for the RESCUE Investigators. Randomized comparison of rescue angioplasty with conservative management of patients with early failure of thrombolysis for acute anterior myocardial infarction. Circulation 1994;90:2280–4.
- ↵Kern MJ, Aguirre F, Bach R, Donohue T, Siegel R, Segal J. Augmentation of coronary blood flow by intra-aortic balloon pumping in patients after coronary angioplasty. Circulation 1993;87:500–11.
- ↵Ohman EM, George BS, White CJ, et al., for the randomized IABP Study Group. Use of aortic counterpulsation to improve sustained coronary artery patency during acute myocardial infarction. Results of a randomized trial. Circulation 1994;90:792–9.
- Califf RM, Topol EJ, George BS, et al., and the TAMI Study Group. Hemorrhagic complications associated with the use of intravenous tissue plasminogen activator in treatment of acute myocardial infarction. Am J Med 1988;85:353–9.