Coronary Angioplasty in Acute Myocardial Infarction: Primary, Immediate Adjunctive, Rescue, or Deferred Adjunctive Approach?

Subject Review

Coronary Angioplasty in Acute Myocardial Infarction: Primary, Immediate Adjunctive, Rescue, or Deferred Adjunctive Approach?

ROBERT D. SIMARI, M.D., PETER B. BERGER, M.D., MALCOLM R. BELL, M.B.,B.S., RAYMOND J. GIBBONS, M.D., AND DAVID R. HOLMES, JR., M.D.

• Objective: To address the current clinical applica-tions, outcomes, and limitations of coronary angioplasty in the setting of acute myocardial infarction.

• Design: We review the results of several large trials in which various strategies of thrombolysis and primary, immediate adjunctive, rescue, or deferred adjunctive coronary angioplasty were used in patients with acute myocardial infarction.

• Material and Methods: Four strategies for the utilization of angioplasty in myocardial infarction have been developed and are based on the timing and concurrent use of thrombolytic therapy.

• Results: Primary coronary angioplasty without prior thrombolytic therapy is as effective as thrombolytic therapy for salvaging myocardium. Re-sults of a meta-analysis of recent trials suggest poten-tial benefits of increased survival and decreased reinfarction in comparison with the results of thrombolysis in recent trials. Immediate adjunctive angioplasty after thrombolytic therapy has been tested in three large, randomized trials. The results suggest that this strategy is associated with increased

During the past 2 decades, an increased understanding of the pathogenesis of acute myocardial infarction has led to dra-matic changes in patient care with the application of thrombolytic therapy and coronary angioplasty. First, dur-ing the late 1970s, the landmark work of Reimer and Jennings and their colleagues1·2 described the wavefront phe-nomenon of myocardial necrosis during experimental coro-nary artery occlusion in dogs. This wavefront extends from subendocardium to subepicardium, is completed in a com-plex and rapid time frame, and is modified by the presence of collaterals. In their model, 70% of the myocardium at risk

From the Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic Rochester, Rochester, Minnesota.

Address reprint requests to Dr. R. D. Simari, Division of Cardiovascular Diseases, Mayo Clinic Rochester, 200 First Street SW, Rochester, MN 55905.

risks without benefits of increased survival or im-proved left ventricular function. Rescue angioplasty may be helpful after failed thrombolytic therapy. On-going randomized trials might further clarify the ben-efits of rescue angioplasty. Because of the inherent difficulty in the noninvasive identification of patients with persistent reocclusion, diagnostic coronary angiography early after thrombolytic therapy may be necessary. Deferred adjunctive angioplasty during the weeks after infarction to prevent recurrent ischemia was not shown to decrease mortality or reinfarction in two large trials.

• Conclusion: Primary coronary angioplasty is the treatment of choice for patients with contraindica-tions to thrombolytic therapy. Certain high-risk sub-groups may also benefit from primary angioplasty.

(Mayo Clin Proc 1994; 69:346-358)

ECSG = European Cooperative Study Group; GISSI = Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico; rt-PA = recombinant tissue-type plasminogen acti-vator; ΤΑΜΙ = Thrombolysis and Angioplasty in Myocardial Infarction; TIMI = Thrombolysis in Myocardial Infarction

was infarcted within 3 hours after coronary artery occlusion. Second, the critical role of acute thrombosis in the initiation of clinical myocardial infarction was elegantly demon-strated in the studies by DeWood and colleagues,3 who observed a high frequency of total coronary artery occlu-sions during the early evolution of myocardial infarction. Initial studies of coronary thrombolysis used intracoronary administration of thrombolytic agents,4 but this approach was gradually replaced by intravenous administration of these agents to decrease the time to treatment and to allow wider utilization.5·6 Since then, several large, randomized trials have demonstrated the value of intravenously admin-istered thrombolytic agents during acute myocardial infarction.712

During the same period in which thrombolysis was ini-tially studied, the successful use of coronary angioplasty in patients with stable angina, as originally introduced by

Mayo Clin Proc 1994; 69:346-358 346 ©1994 Mayo Foundation for Medical Education and Research

Mayo Clin Proc, April 1994, Vol 69 CORONARY ANGIOPLASTY IN ACUTE MYOCARDIAL INFARCTION 347

Griintzig and associates,13 led other investigators to believe that it might have a role in the immediate treatment of myocardial infarction as a means of mechanical revas-cularization.14 Currently, early reperfusion is considered critically important for decreasing mortality after myocar-dial infarction. Increasing awareness of the limitations of thrombolytic therapy (including the frequent presence of contraindications among patients with acute myocardial infarction, less than universal reperfusion rates, and bleeding complications) has prompted assessment of the role of coro-nary angioplasty in patients with acute myocardial infarction. In this review, we address the current clinical applications, outcomes, and limitations of coronary angioplasty in the setting of acute myocardial infarction.

Although the terminology used to describe the type and timing of coronary angioplasty in the setting of acute myo-cardial infarction has been inconsistent, the following classi-fication is both logical and easily understood (Fig. 1):

1. Primary coronary angioplasty: dilation of an infarct-related artery during the acute phase of myocardial infarction without prior administration of thrombolytic therapy

2. Immediate adjunctive coronary angioplasty: routine dilation of an infarct-related artery as soon as possible after the administration of a thrombolytic agent

3. Rescue coronary angioplasty: dilation of an infarct-related artery immediately after thrombolysis has failed

4. Deferred adjunctive coronary angioplasty: dilation of an infarct-related artery within the first week after myo-cardial infarction to prevent recurrent ischemia.

INITIAL REPORTS The first reported use of coronary angioplasty in the setting of acute myocardial infarction was in 1982 by Meyer and associates,15 who reported the outcome of 21 patients who underwent coronary angioplasty 20 to 60 minutes after intracoronary administration of streptokinase. Of the infarct-related arteries, 81% were successfully dilated (the initial mean extent of stenosis was decreased from 90 to 58%). Failure of coronary angioplasty was due to the inabil-ity to cross the lesion with a fixed-wire balloon catheter in three patients and the inability to engage the guide catheter in one patient. The investigators noted that the procedure was "much easier" in these patients than in patients with chronic stable angina. This report also included the first descrip-tion of the successful use of coronary angioplasty in a pa-tient with cardiogenic shock. Although the investigators reported no major procedural complications, one patient died and an autopsy showed diffuse epicardial bleeding, another patient had reinfarction, and four patients required coronary artery bypass grafting during hospitalization. Four to 6 months after angioplasty, 77% of the patients had class I or II symptoms.

Primary PTCA

STt / yr Immediate adjunctive PTCA

+ i—► Thrombolysis <^ chest pain \ - N . Rescue PTCA

? thrombolysis ■ Deferred adjunctive PTCA

Hours » Days

Fig. 1. Strategies for coronary angioplasty in acute myocardial infarction. PTCA = percutaneous transluminal coronary angioplasty; ST = ST segment.

In 1983, the Mid America Heart Institute published the first of several reports that detailed its experience with angioplasty in the setting of acute myocardial infarction.16 In 41 patients, including 13 who underwent primary coronary angioplasty without use of thrombolytic agents, the primary success rate was 85%, and the mean extent of residual stenosis was 30%. At follow-up coronary angiography of the 41 patients 10 days after angioplasty, the patency rate of the infarct-related arteries was 89%. In addition, left ven-tricular ejection fraction had increased from 44% (before primary angioplasty) to 60% at 10 days. At clinical fol-low-up 7 months later, 91% of the patients had class I symptoms.

The initial Mayo Clinic experience with coronary angioplasty for acute myocardial infarction was reported in 1985;1711 patients underwent primary coronary angioplasty, and 11 had intracoronary administration of streptokinase. Reperfusion was achieved in 10 patients (91%) in the pri-mary angioplasty group and in 9 (82%) in the intracoronary thrombolytic group. Subsequently, however, coronary ar-tery bypass grafting was performed in nine of the patients (82%) who had received intracoronary thrombolysis but in only three (27%) of those who had undergone primary coro-nary angioplasty. The clinical decision for further revascularization in the patients treated with only streptoki-nase was based on the presence of severe residual stenosis after intracoronary administration of thrombolytic therapy in six patients.

After these initial reports, Erbel and colleagues18 pub-lished the results of the first randomized trial designed to compare a strategy of both intravenous and intracoronary administration of streptokinase with a strategy of coronary angioplasty after intravenous and intracoronary administra-tion of streptokinase. In that study, patency was achieved in

348 CORONARY ANGIOPLASTY IN ACUTE MYOCARDIAL INFARCTION Mayo Clin Proc, April 1994, Vol 69

90% and 86% of the two groups, respectively. Angioplasty was successful (defined as an improvement of more than 20% in the narrowing of the coronary artery lumen) in only 65% of patients. The mean residual stenosis after these two strategies was more severe in the thrombolytic group (73%) than in the group that underwent thrombolysis and angioplasty (51%). Despite this difference in the residual severity of the stenosis, the in-hospital clinical reocclusion rate was similar between the two groups; however, the reocclusion rate was 32% for patients in whom angioplasty was unsuccessful and 7% for those in whom it was success-ful. Mortality and global left ventricular function were also similar. Thus, the clinical strategy of performing angioplasty after thrombolytic therapy did not result in in-creased improvement in left ventricular function or in clini-cal outcome.

PRIMARY CORONARY ANGIOPLASTY Since the early reports that described the safety and efficacy of primary coronary angioplasty, several large series of con-secutive patients treated with primary coronary angioplasty without prior thrombolytic therapy have been published (Table l).19"24 The largest of these series was reported by O'Keefe and colleagues19 from the Mid America Heart Insti-tute. During an 8-year period, they performed primary coro-nary angioplasty in 500 patients; their success rate was 94% (defined as residual stenosis of 40% or less in the luminal diameter of the artery). The need for in-hospital coronary artery bypass grafting was 2%, and overall mortality during hospitalization was 7.2%. Reocclusion during hospitaliza-tion, however, occurred in 15% of the patients. The success and complication rates in the study by O'Keefe and asso-ciates are comparable -to those reported in other smaller single-center series. A recent preliminary report of the multicenter Primary Angioplasty Revascularization group24

provided similar results. An important aspect of these large series of patients who

underwent primary angioplasty is that they include many patients who would have been ineligible for thrombolytic

therapy because of traditional exclusion criteria. In the series by O'Keefe and colleagues,19 56% of the patients would not have been candidates for thrombolysis because of prevailing contraindications, such as advanced age, late in-tervention, severe hypertension, cardiogenic shock, or a his-tory of cerebrovascular accidents. The overall mortality rate for the subgroup of patients without thrombolytic contraindications was only 1.8%, a percentage that compares favorably to the mortality rate in most thrombolytic trials.

Follow-Up.—Follow-up of patients who underwent pri-mary angioplasty reveals excellent long-term survival. O'Keefe and coworkers19 reported an overall 1-year survival rate of 95% and an overall 5-year survival rate of 84%. The 3-year survival rate was 92% in patients with single-vessel disease and 87% in those with multivessel disease. Rothbaum and colleagues21 noted an overall survival rate of 95% at 20 months after successful angioplasty.

Although the reported complication rate with primary angioplasty in these single-center series seems low, multicenter data suggest that the risk of major bleeding events is similar to that associated with thrombolytic therapy. O'Keefe and associates19 reported a 3% risk of bleeding complications, including retroperitoneal or vascu-lar hemorrhage that necessitated vascular repair or transfu-sion. No periprocedural strokes or myocardial ruptures were noted in their series. Further analysis of a subset of this series failed to reveal significant differences in success or complication rates based on the infarct-related artery.25 In the multicenter Primary Angioplasty Revascularization study,26 in which 11% of the patients received adjunctive thrombolytic therapy, 12% of patients who did not undergo coronary artery bypass grafting required blood transfusions. Bleeding at the vascular access site and intracerebral bleed-ing were confirmed in 66% and 0.5% of patients, respec-tively. In the Primary Angioplasty in Myocardial Infarction Study,27 bleeding that necessitated transfusion occurred in 12.3% of patients in the angioplasty group and in 8.0% in the thrombolytic group (P = 0.16). Thus, the bleeding risk associated with the clinical use of coronary angioplasty for

Table 1.—Reported Nonrandomized Consecutive Series of Primary Coronary Angioplasty for Acute Myocardial Infarction*

Reference

O'Keefe et al19

Brodie et al20

Rothbaum et al21

Kimura et al22

Marco et al23

O'Neill et al24

Total

Patients (no.)

500 202 151 58 43

206 1,160

Success (%)

94 91 87 88 95 97 93

CABG (%)

2.0 4.4 1.5 NA 6.9 6.0 3.4

Death (%)

7.2 8.9 9.0

NR 13.9 4.0 7.4

Reocclusion (%)

15 NR

9 14

NR NR 13.7

*CABG = coronary artery bypass grafting; NA = not available; NR = not recorded.


acute myocardial infarction may be comparable to the risk associated with the'use of thrombolytic agents.

Restenosis.—Restenosis after primary angioplasty is a topic of intense interest. Simonton and associates28 reported a restenosis rate of 19% among 79 patients in whom angioplasty for acute myocardial infarction was successful and 35% among 206 patients who underwent elective coro-nary angioplasty. Nonetheless, 90% of the group who un-derwent angioplasty for infarction received adjunctive thrombolytic therapy. In addition, during the initial hospital-ization, reocclusion occurred in 13% of this group, an out-come that led to similar overall reoccurrence rates in the two groups. Rothbaum and colleagues21 reported a restenosis rate of 31% in their series of 151 patients. In a recent preliminary report from France with angiographie follow-up in 100% of the patients,29 restenosis was found in 20% who underwent primary angioplasty and in 16% who received thrombolysis in addition to angioplasty. Acute reocclusion occurred, however, in approximately 25% of patients in each group. Therefore, despite evidence that restenosis rates after angioplasty for myocardial infarction might be lower than the rate in elective cases, this benefit may be offset by the clinical problem of early acute reocclusion, which usually occurs during the initial hospitalization.

Selection of Patients.—Support for coronary angioplasty in patients who are believed to be poor candidates for thrombolytic therapy is increasing. One such group consists of patients in whom cardiogenic shock develops in the set-ting of acute myocardial infarction. Several retrospective series have suggested a survival benefit among patients after successful coronary angioplasty in comparison with histori-cal series of patients treated medically. One multicenter series30 reported outcomes of angioplasty in 69 patients in whom cardiogenic shock developed during myocardial infarction. Angioplasty was successful in 71% of the pa-tients, and the overall hospital survival rate was 55%. Among the patients in whom angioplasty was successful, 69% survived 7 days, and 55% were still alive at late follow-up of 32 months. Among the patients in whom angioplasty was unsuccessful, only 20% survived 7 days, all of whom survived tò late follow-up.

Similar data from our institution for 45 patients with cardiogenic shock31 revealed a hospital survival rate of 71% among those in whom coronary angioplasty was successful and 29% among those in whom it was unsuccessful. At a mean follow-up of 2.3 years, survival was 80% among pa-tients dismissed from the hospital. Although these studies were retrospective and nonrandomized, the survival rates among patients in whom angioplasty was successful are an improvement over previously reported survival rates among patients with cardiogenic shock who received medical therapy (including thrombolytic therapy). The high mortal-

ity rate among the patients with unsuccessful results of angioplasty may represent the natural history of the high-risk populations studied rather than a direct detrimental effect of angioplasty.

Thrombolytic therapy has often been withheld from pa-tients with a presumed high risk of bleeding complications. Up to 15% of all patients excluded from receiving thrombolytic therapy may have a history of cerebrovascular disease, recent prolonged cardiopulmonary resuscitation, bleeding disorders, severe hypertension, or recent opera-tion.32 Coronary angiography and primary coronary angioplasty are the treatments of choice in this group of patients, as long as they do not also have exclusions for administration of heparin.

At least 20% of patients with acute myocardial infarction seek medical attention beyond the traditional time frame for thrombolysis. A recent study compared the outcome of coronary angioplasty in 139 patients with myocardial infarction and ongoing ischemia who sought medical help 6 to 48 hours after the onset of chest pain with the outcome in 117 patients who sought help within 6 hours after onset.33

The success and complication rates were similar in the two groups, and the mortality rate in each group was 13.7%. Nonetheless, among the patients who sought aid late, the mortality rate was 43.3% for those in whom angioplasty was unsuccessful and 5.5% among those in whom it was success-ful. Although the investigators ascribed this substantial difference in mortality to a detrimental effect of failed coro-nary angioplasty, the conclusion is highly speculative be-cause the patients in whom angioplasty failed were, at baseline, at considerably higher risk (they were older, they had greater impairment of left ventricular function, and they had a high frequency of multivessel disease). In a large consecutive series, failed primary angioplasty was associ-ated with a 31% in-hospital mortality rate, whereas it was 4.8% after successful angioplasty.34 The group with unsuc-cessful results, however, included more patients with multivessel disease, prior myocardial infarctions, and pres-ence of cardiogenic shock. Further study is needed to deter-mine whether unsuccessful primary coronary angioplasty increases mortality in comparison with conservative therapy.

In most of the major clinical trials, advanced age is listed as a primary contraindication to thrombolytic therapy in at least 10% of patients who are otherwise eligible. In elderly patients, thrombolytic therapy is associated with an in-creased risk of intracranial bleeding, and the morbidity and mortality rates have been high.9·10 In the Second Interna-tional Study of Infarct Survival,10 although thrombolytic therapy was associated with a significant decrease in mortal-ity, the in-hospital mortality rate for patients 70 years or older was 16% in the treatment group (streptokinase and aspirin) and 24% in the placebo group. In the Gruppo


Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI) study,' patients older than 75 years had an in-hospital mortality rate of 29% in the thrombolytic group and 33% in the control group. The 1-year mortality rates in these groups were 43% and 46%, respectively. In these patients, benefits from thrombolytic therapy may be substantial in comparison with conservative treatment; thus, advanced age is only a relative contraindication. Because of the increased risks, however, alternative revascularization strategies are important.

The use of coronary angioplasty in elderly patients with myocardial infarction has been reported in several series. At the Mid America Heart Institute, Lee and coworkers35 de-scribed the outcome of 105 patients older than 70 years who underwent primary coronary angioplasty for acute myocar-dial infarction. Angioplasty was successful in 91% of the patients, and the hospital mortality rate was 18%. Vascular complications occurred in 2%, and the 1-year survival rate was 73%. A similar report from the University of Michi-gan36 indicated an overall success rate of 66% with coronary angioplasty in 35 patients older than 70 years; the hospital mortality rate was 35%, and the vascular complication rate was 14%. In a preliminary report from the Primary Angioplasty Revascularization group,24 the mortality rate was 8% in patients older than 70 years. These results are comparable to the data from the major randomized thrombolytic trials. Whether primary coronary angioplasty should be the principal strategy for early recanalization in these patients can be ascertained only through an appropriate randomized, prospective trial.

A retrospective study showed that patients who had myo-cardial infarction and bundle-branch block or ST-segment depression and who received no thrombolytic therapy had a fivefold increase in mortality rate in comparison with pa-tients who met standard criteria and received thrombolytic therapy.32 In the GISSI study,9 patients with bundle-branch block received no benefit from thrombolytic therapy; in contrast, patients with left bundle-branch block in the Sec-ond International Study of Infarct Survival10 had decreased mortality. No survival benefits were demonstrated in pa-tients with ST-segment depression or normal ST segments in either trial. The lack of clear benefit in these groups could reflect the heterogeneity of the populations involved. Thus, diagnostic emergency angiography followed by emergency angioplasty, if indicated, is an important therapeutic option in patients with a history compatible with myocardial infarction but without diagnostic electrocardiograms.

Patients who have previously undergone coronary artery bypass grafting have also been excluded from most major thrombolytic trials. Because of the potentially large thrombotic burden present in vein grafts, primary coronary angioplasty has been advocated as a means of reperfusion for

acute infarct-related vein grafts. Kahn and colleagues37 re-ported the results of primary coronary angioplasty in 72 patients who had previously undergone coronary artery by-pass grafting. In this group, the infarct-related artery was a saphenous vein graft in 48 patients (67%). The success rate was 85% in these patients and 100% in patients with a native infarct-related artery. The overall in-hospital mortality rate was 10%.

Randomized Trials.—In 1986, O'Neill and associates38

reported the results of a trial in which 56 patients with acute myocardial infarction were randomly assigned to either pri-mary coronary angioplasty or intracoronary administration of streptokinase. Recanalization was achieved in 85% and 83% of the two groups, respectively; the residual stenosis was less severe in the angioplasty group than in the thrombolytic group (43% versus 83%; P<0.001). Serial contrast ventriculography showed a considerable increase in the global ejection fraction of patients in the angioplasty group in comparison with those in the thrombolytic group. Thus, angioplasty seemed to be more effective for alleviat-ing the underlying coronary stenosis and may have been beneficial in preserving ventricular function. Unfortunately, the study was limited by relatively small numbers, lack of complete angiographie follow-up, and comparison with intracoronary lysis, which is no longer a commonly used strategy.

One of the problems in assessing the relative merits of primary coronary angioplasty and thrombolytic therapy is that different patient populations have been studied with each technique. In addition, controlled data for angioplasty are more limited than are data for thrombolytic therapy, which has been the focus of controlled studies in more than 100,000 patients worldwide. The large patient numbers in the thrombolytic trials have allowed the use of mortality as an end point. Because of the small numbers involved in the randomized trials of primary coronary angioplasty and thrombolysis, end points other than mortality were selected. Possible alternatives include global or regional left ventricu-lar function, recurrent ischemie events, or quantification of myocardial salvage. Ventricular function is an insensitive end point because it does not depend only on size of infarct. Loading conditions, medications, degree of catecholamine stimulation, and function of the noninfarcted myocardial segment can all substantially affect ventricular function. Recurrent ischemia probably reflects the degree of residual coronary stenosis and is not a direct measure of myocardial salvage and therefore should be considered a secondary end point.

Recently, the radionuclide technetium-99m sestamibi has been used to measure the amount of myocardium salvaged as a result of immediate reperfusion therapy. This radionuclide can be injected intravenously in the emergency department


before reperfusion therapy and, because redistribution does not occur, the patient can undergo scanning hours after reperfusion for assessment of the extent of myocardial hypoperfusion ("myocardium at risk") that was present at the time of the initial examination. Follow-up images obtained later during hospitalization provide a measure of final size of infarct, and the change between the initial and later images indicates the amount of myocardial salvage. Because this strategy considers the wide variation in myocardium at risk, myocardial salvage determined by serial technetium-99m sestamibi imaging may be a more sensitive end point than regional or global left ventricular function for immediate reperfusion trials. In a pilot study performed at our institu-tion, Behrenbeck and colleagues39 demonstrated a decrease in mean size of defect from 48 to 29% of the left ventricle for patients in whom direct coronary angioplasty was success-ful. In a separate group of patients with persistent coronary occlusion during myocardial infarction, size of defect re-mained unchanged. Using this technique, the investigators identified factors associated with increased myocardial sal-vage.40 Anterior infarctions had larger areas of myocardium at risk than did inferior infarctions and thus larger poten-tial areas of salvage. They also found that the severity of hypoperfusion present within the area at risk was inverse-ly related to the amount of myocardium salvaged. This factor may represent the influence of collateral flow on the effects of reperfusion, as demonstrated previously in animal models.

Recently, the Mayo Clinic reported the final results of a randomized trial of intravenously administered thrombolytic therapy versus primary coronary angioplasty in acute myo-cardial infarction; myocardial salvage quantified by serial technetium-99m sestamibi ràdionuclide scanning was an end point.41 All patients 80 years or younger with at least 30 minutes but no more than 12 hours of chest pain associated with ST-segment elevation in two contiguous leads or ST depression in leads V! through V3 were eligible. Of the 108 patients enrolled in the study, data were complete in 103. Primary coronary angioplasty was successful in 43 of 45 patients (96%). Two patients had patent infarct-related ar-teries. Thrombolytic therapy with recombinant tissue-type plasminogen activator (rt-PA) (Duteplase, in the same dos-age as used in the Third International Study of Infarct Sur-vival) was administered to 56 patients. The extent of myo-cardium at risk was similar: 30% of the left ventricle in the rt-PA group and 27% in the angioplasty group. Myocardial salvage was also similar between the two groups : 15 % of the left ventricle in the rt-PA group and 13% in the angioplasty group. Mechanical revascularization was used before dis-missal, however, for 20 of the 56 patients (36%) in the thrombolytic group (coronary angioplasty in 16 and coro-nary artery bypass grafting in 7, including 3 in whom

angioplasty was unsuccessful) and for 7 (16%) in the angioplasty group (coronary angioplasty in 1 and coronary artery bypass grafting in 6). In the subsets of patients with anterior or inferior infarcts, neither therapy was advanta-geous. In each of the treatment groups, two patients died. No difference in left ventricular ejection fraction was noted at dismissal or at 6 weeks after infarction between the two groups (Fig. 2). Cost analysis revealed no significant differ-ences between the strategies. Patients in the angioplasty group, however, had briefer hospital stays (P = 0.01), fewer readmissions within 6 months (P = 0.04), and lower 6-month follow-up costs (P = 0.03) than did those in the rt-PA group. Thus, the strategies of initial primary angioplasty or thrombolytic therapy followed by further revascularization, if needed, resulted in a similar degree of myocardial salvage. Primary angioplasty is associated with less recurrent ischemia and therefore fewer subsequent revascularization procedures.

Results from a randomized trial in the Netherlands of intravenously administered streptokinase versus primary angioplasty seem to confirm the fact that the latter is associ-ated with less recurrent ischemia.42 The principal end points in that trial were recurrent ischemia during hospitalization, left ventricular ejection fraction, and coronary patency. In the study, 72 patients received 1.5 million U of streptoki-nase, and 70 underwent primary coronary angioplasty. Re-current ischemia was present in 38% of the patients treated with streptokinase and in 9% of those treated with angioplasty. Left ventricular function at dismissal as as-sessed by ejection fraction was higher in the angioplasty group than in the thrombolytic group (51% versus 45%; Fig. 2), as was angiographie patency of the infarct-related artery (91% versus 68%). Additional revascularization procedures were performed in 42% of the patients in the thrombolytic group and in 14% of the angioplasty group.

The Primary Angioplasty in Myocardial Infarction trial27

analyzed the use of rt-PA versus primary coronary angioplasty; the principal end points were combined mortal-ity and recurrent in-hospital ischemia rates in 395 patients. The rate of nonfatal reinfaretion or death within 6 weeks was 12% in the thrombolytic group and 5.1% in the angioplasty group (P = 0.02). The overall mortality rates between the groups were not significantly different (2.6% in the angioplasty group and 6.5% in the thrombolytic group; P = 0.06). Subgroup mortality analysis revealed a benefit of angioplasty in high-risk patients (those who had anterior infarcts, were older than 70 years, or had heart rates of more than 100 beats/min at admission). Recurrent ischemia was also more frequent in the thrombolytic group than in the angioplasty group (28% versus 10%; P<0.05). In the Pri-mary Angioplasty in Myocardial Infarction trial, all patients received diltiazem hydrochloride, a drug with no proven


80

p=0.004

Mayo Netherlands

Lysis

PTCA ■.· - 1

Ύΐ*'

Mayo PAMI

Lysis

PTCA

Fig. 2. Left ventricular ejection fraction in randomized trials of coronary angioplasty versus thrombolysis in acute myocardial infarction. A, At dismissal. B, At 6 weeks after infarction. PAMI = Primary Angioplasty in Myocardial Infarction; PTCA = percutaneous transluminal coronary angioplasty.

benefit in Q-wave myocardial infarction, but the protocol did not necessitate ß-adrenergic blockers.

The rate of stroke in the thrombolytic group in this trial was 3.5%, whereas it was 1.1 to 1.5% in the GISSI and Second International Study of Infarct Survival trials.9·10 Four deaths in the thrombolytic group were attributed to intracra-nial hemorrhage. The rates of death and reinfarction in the thrombolytic group (12.0%) were higher than in the conser-vative group in the Thrombolysis in Myocardial Infarction II (TIMI II) Study (6.3%).43 Thus, although differences existed in each of these study populations, the thrombolytic group seemed to have more adverse outcomes than might have been expected. As such, extrapolating these data to larger populations is difficult.

A synthesis of the trials of primary angioplasty compared with thrombolysis necessitates assessment of the patient populations studied, the methods used, and the end points considered. Each study compared primary angioplasty with thrombolysis. All three studies included patients who were not included in earlier thrombolytic trials. The Primary Angioplasty in Myocardial Infarction and the Mayo Clinic trials included patients older than 75 years. All the studies included patients with signs of myocardial infarction up to 12 hours after the onset of symptoms. Each study used lytic agents and dosing regimens that had verified efficacy. Al-though each trial stated exclusion of patients with cardio-genie shock, the Netherlands trial included nine patients in Killip class 3 or 4 and had a high percentage of patients with three-vessel disease (31%).

The principal end points of these studies differed. In the Primary Angioplasty in Myocardial Infarction trial, the pro-spectively analyzed end point was recurrent ischemia or death. The Netherlands trial used recurrent ischemia before dismissal, left ventricular ejection fraction, and vessel pa-tency. The Mayo Clinic trial used myocardial salvage. None

of these trials was designed to detect differences in mortality or in-hospital reinfarction. In fact, none of these studies alone had more than 25% power to detect an overall decrease of 2% in mortality.

In light of the similarities of the populations studied and the study designs, we performed a meta-analysis of the three studies in which in-hospital mortality and reinfarction are used as end points (Table 2). This analysis suggests a decreased risk of mortality or reinfarction with primary angioplasty and that larger randomized trials might detect such differences.

The data from these trials provide some unifying conclu-sions. With the use of sensitive measures of myocardial salvage, both strategies seem equivalent. The apparent dis-crepancy in ejection fraction data (Fig. 2) may be due to the benefits of angioplasty in the more critically ill patients in the Netherlands trial. Primary angioplasty is associated with less recurrent ischemia and further need for revascularization. Certain high-risk subgroups may also benefit from angioplasty rather than from thrombolytic therapy. Meta-analysis of these data suggests potential ben-efits of angioplasty in terms of death or reinfarction. This issue can be clarified only by large-scale, prospective, ran-domized trials and comparison with new strategies for the administration of thrombolytic agents (such as prehospital or rapid dosing). In addition, these trials represent the best efforts of experienced investigators. Generalization of these results to a larger group of clinicians might be difficult.

Currently, the greatest advantages of primary angioplasty for acute myocardial infarction are immediate revas-cularization for patients in whom thrombolytic therapy is contraindicated and a decrease in the number of recurrent ischemie events during hospitalization. Such a strategy, however, necessitates a complex logistic approach—an ex-perienced catheterization team must be on call 24 hours a


Table 2.—Meta-Analysis of the Randomized Trials of Primary Angioplasty Versus Thrombolysis

in Acute Myocardial Infarction*t

Trial

PAMI Netherlands Mayo

Total

PAMI Netherlands Mayo

Total

PTCA Ly

No. of patients

195 70 47

312

195 70 47

312

Events N n n f

No. % patients

In-hospital mortality^ 5 2.6 200 0 0.0 72 2 4.3 56 7 2.2 328

In-hospital reinfarction^ 5 2.6 200 0 0.0 72 1 2.1 56 6 1.9 328

sis

Events

No.

13 4 2

19

13 9 3

25

%

6.5 5.6 3.6 5.8

6.5 12.5 5.4 7.6

*PAMI = Primary Angioplasty in Myocardial Infarction; PTCA = percutaneous transluminal coronary angioplasty.

fThe method used to estimate a common odds ratio was to combine the three hypergeometric likelihood functions and use the maxi-mal likelihood estimate. Confidence limits were determined by setting the likelihood ratio χ2 equal to the 0.05 critical value. P values were based on the Mantel-Haenszel test.

ÌThe odds ratio for in-hospital mortality with thrombolysis versus angioplasty is 2.68 (95% confidence limits, 1.16 and 6.92; P = 0.023).

§The odds ratio for in-hospital reinfarction with thrombolysis ver-sus angioplasty is 4.22 (95% confidence limits, 1.82 and 11.46; P = 0.0008).

day and patients must be transferred rapidly to the catheterization laboratory. The cost of building, equipping, and staffing these centers should not be underestimated. Moreover, because candidates for thrombolysis represent only 16 to 37% of patients'with myocardial infarction,912·32·44

primary angioplasty might be the only available option for acute revascularization in a large population of patients.

IMMEDIATE ADJUNCTIVE CORONARY ANGIOPLASTY The major rationale for the strategy of intravenously admin-istered thrombolytic therapy followed by immediate adjunc-tive coronary angiography is that in patients in whom thrombolytic, therapy fails or in those who have severe re-sidual stenosis, angioplasty might be an alternative treat-ment. This approach has been studied in three large, pro-spective, randomized trials.43·45·46 These studies, however, had important differences that must be appreciated for ad-equate interpretation and understanding of the results. In the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) I study,46 all patients received 150 mg of rt-PA intravenously and then were directly transferred to the catheterization laboratory. Of the 386 patients original-ly enrolled in the study, 197 had successful thrombolysis

(TIMI grade 2 or 3 flow) with severe residual stenosis (50% or more) in the infarct-related artery and were random-ized to either immediate adjunctive angioplasty or elective coronary angioplasty 7 to 10 days after infarction. Patients in whom reperfusion was not achieved were excluded from randomization and underwent rescue angioplasty. The pri-mary end point of this study was global left ventricular function.

In the TIMI II A trial43 and the European Cooperative Study Group (ECSG) trial,45 patients received rt-PA intrave-nously (150 or 100 mg in the TIMI trial and 100 mg in the ECSG trial) in the emergency department and were random-ized to undergo immediate catheterization followed by angioplasty or delayed catheterization at 18 to 48 hours (TIMI trial) or conservative therapy (ECSG trial). An as-sessment of global left ventricular function was the major end point of these studies.

The mean left ventricular ejection fraction was somewhat higher in the patients in TAMI I than in the other two studies (Fig. 3) because only patients with patent infarct-related arteries were eligible for randomization. No differences in left ventricular function were noted, however, between the immediate adjunctive therapy and the conservative therapy groups. Although these studies were not appropriately sized to detect a mortality difference by treatment, all three showed a trend toward increased mortality in the immediate adjunctive angioplasty group, and the differences were sta-tistically significant in the ECSG study (Fig. 4). The need for emergency bypass operation and the frequency of bleed-ing complications were increased in the immediate adjunc-tive intervention group in each study. Reocclusion and recurrent ischemia occurred at similar frequencies in the immediate adjunctive angioplasty and conservative groups

<£

If s

a 50-

40-

30

20

10-

o-

■ Immediate ■ Conservative

TAMI I TIMI HA ECSG

Fig. 3. Left ventricular function in immediate and conservative therapy groups in three trials of thrombolysis and coronary angioplasty: Thrombolysis and Angioplasty in Myocardial Infarction (TAMI /), Thrombolysis in Myocardial Infarction (TIMI II A), and European Cooperative Study Group (ECSG).


6-

i; TAMI 1 TIMI HA ECSG

■ Immediate

Fig. 4. Mortality in immediate and conservative groups in three trials of thrombolysis and coronary angioplasty: Thrombolysis and Angioplasty in Myocardial Infarction (TAMI /), Thrombolysis in Myocardial Infarction (TIMI II A), and European Cooperative Study Group (ECSG).

in all three studies. Thus, the routine performance of imme-diate adjunctive cardiac catheterization after thrombolytic therapy was associated with a greater risk of bleeding and a greater need for bypass operation without a demonstrable improvement in left ventricular function.

These conclusions are limited, however, by several im-portant factors. First, the immediate adjunctive angioplasty arms of the ECSG and TIMI Π A trials included more high-risk patients than did the group assigned to conservative therapy. In the ECSG trial, the invasive strategy included seven patients in cardiogenic shock, whereas the non-invasive arm included only one. Second, almost 30% of the patients randomized to "early angioplasty in the TIMI II A trial underwent coronary angiography but not angioplasty. Third, these three trials used the same thrombolytic agent; thus, the results may not necessarily be applicable to other agents. Despite these limitations, the evidence against the routine performance of immediate adjunctive angioplasty after uncomplicated thrombolysis is substantial and has in-fluenced the treatment of acute myocardial infarction world-wide.

As a result of the coupling of coronary angiography and coronary angioplasty in these studies, the benefits of only coronary angiography without routine angioplasty to iden-tify thrombolytic failures and to determine the extent of coronary artery disease have not been examined. Angioplasty of a patent infarct-related artery (TIMI grade 2 or 3) may be avoided in a stable patient, especially because approximately 15% of infarct-related lesions contain large quantities of thrombus that may undergo continued lysis and become angiographically insignificant 7 to 10 days after infarction.46

Adverse clinical outcomes in patients who have received combination therapy with a thrombolytic agent and coronary angioplasty may have a pathologic basis (Fig. 5). Autopsy specimens from patients who have received combination thrombolytic and angioplasty therapy have demonstrated hemorrhage into portions of the arterial wall at the site of dilation. Waller and associates47 noted severe hemorrhage surrounding the sites of coronary angioplasty in four of four patients who died after receiving combination therapy, but they could not identify similar bleeding in nine patients who died after treatment with only primary coronary angioplasty.

RESCUE CORONARY ANGIOPLASTY Thrombolytic therapy has yielded variable reperfusion rates; they range from 55 to 85% and depend on the route and agent used, the time from the onset of chest pain, and other less understood variables.810 For patients in whom the infarct-related artery remains occluded, rescue angioplasty may have merit because mortality rates in such patients are in-creased.48·49 None of the prospective, randomized trials of intravenous thrombolysis followed by immediate adjunctive coronary angioplasty, however, were able to evaluate a strat-egy of rescue angioplasty; the TAMI I trial excluded such patients from randomization. Because the patients assigned to conservative therapy in the TIMI and ECSG trials did not undergo immediate angiography, analysis of this important subgroup of patients in whom thrombolytic therapy failed was precluded.

In 1986, a retrospective study from the University of Michigan50 compared the results of angioplasty in 13 pa-tients whose infarct-related artery remained occluded de-spite thrombolytic therapy with the results in 13 patients who had successful results of thrombolytic therapy and residual stenosis of 70 to 99%. Among the patients in whom thrombolytic therapy failed, coronary angioplasty resulted in improved global left ventricular function and regional wall motion, and the 10-day ejection fraction in both groups was similar (59%). Thus, in this small group of patients, rescue angioplasty seemed to salvage myocardium to a degree simi-lar to that found with early reperfusion. A similar study5' involving 34 patients demonstrated that patients who under-went rescue angioplasty after thrombolytic therapy failed had a lower ejection fraction at dismissal (36%) than did those who had successful results of reperfusion therapy (50%). The overall survival rate of 89% 4 years after rescue angioplasty, however, suggested a beneficial role of late reperfusion independent of myocardial salvage.

The initial thrombolytic agent used may influence the outcome of rescue angioplasty. A comparison52 between the TAMI I trial, which used rt-PA, and the TAMI II trial, which used a combination of rt-PA and urokinase, showed a higher success rate with rescue angioplasty (96% versus 69%; P =


Fig. 5. Photomicrographs of cross sections from left anterior descending artery of 74-year-old woman with acute anterior myocardial infarction who underwent intracoronary administration of streptokinase and immediate angioplasty. A, At level of angioplasty procedure, intimai tear (along left side of artery) led to adjacent intramedial dissection and focal adventitial hemorrhage. B, Extension of intramedial dissection tract led to formation of large hematoma (at top of artery) and subsequent severe extrinsic luminal compression (at bottom of artery), distal to site of balloon dilation. (Hematoxylin-eosin; A, x20; B, x50.) (Photograph courtesy of Dr. William D. Edwards, Division of Anatomic Pathology, Mayo Clinic.)

0.017), trends toward a lower reocclusion rate (9% versus 15%; P = 0.11), and a lower mortality rate (0% versus 10.4%; P = 0.075) in patients who received combination thrombolytic therapy. Results in patients who underwent rescue angioplasty in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial after receiving single or combination thrombolytic therapy might clarify these findings.53 The rationale for combination therapy is to combine the in-creased early patency rates associated with the "selective" agents with the decreased reocclusion rates of the "nonselec-tive" agents.

In the TAMI phase 5 trial,54 595 patients were randomly assigned to one of three thrombolytic drug regimens (rt-PA, urokinase, or a combination of these agents) and to either immediate cardiac catheterization and potential rescue angioplasty or routine predismissal catheterization and angioplasty. Predismissal patency rates were slightly higher in the immediate catheterization group than in the routine group (94% versus 90%; P = 0.07). The aggressive strategy was associated with improved wall motion in the infarcì region, fewer adverse outcomes, and no substantial increase in the use of blood products. The ability of this trial to study the benefits of rescue angioplasty was limited, however, because the deferred group did not undergo immediate angiography. Such a multicenter trial comparing rescue angioplasty with conservative therapy of occluded infarct-related arteries is currently under way: the Randomized Evaluation of Salvage Angioplasty With Combined Utiliza-tion of Endpoints (RESCUE).

The safety of rescue coronary angioplasty for inferior myocardial infarctions has recently been questioned. Gacioch and Topol55 reported a significant increase in the requirement for cardiopulmonary resuscitation and trends toward increases in the occurrence of ventricular tachycardia or ventricular fibrillation, prolonged hypotension, in-hospi-tal death, and hypoxic brain damage in patients undergoing rescue angioplasty of the right coronary artery in comparison with the left anterior descending coronary artery. Possible mechanisms include the Bezold-Jarisch reflex, distal embolization of thrombus, or presence of acute right ven-tricular infarction. A multicenter retrospective evaluation56

also found increased complications (ventricular fibrillation, second- and third-degree heart block, and acute vessel reocclusion) with rescue angioplasty of the right coronary artery.

A major limitation of the clinical strategy of rescue angioplasty has been the failure of clinical markers to iden-tify patients with successful reperfusion after thrombolytic therapy; thus, all patients must undergo immediate angiography to determine the small number of patients with persistent reocclusion. In the TAMI trials,57 complete reso-lution of ST elevations was highly predictive of successful reperfusion but was applicable to only a small number of patients undergoing thrombolytic therapy. Chest pain com-pletely resolved in only 29% of patients but was associated with a patency rate of 84%. Of interest, neither supraventricular nor ventricular arrhythmias were predictive of reperfusion. In a similar study from Germany,58 a com-bined analysis of three noninvasive markers (reduction in ST


elevation, occurrence of reperfusion arrhythmias, and early peak creatine kinase activity) proved to be both highly sensi-tive (100%) and specific (90%) for patency of the coronary artery. Creatine kinase activity, however, can be determined only after myocardial necrosis. In a study of 82 patients, Shah and colleagues59 demonstrated that the combination of a rapid decrease in pain and ST-segment elevation (moni-tored continuously) was a reliable marker of reperfusion.

Several investigational methods to identify reperfusion prospectively include dynamic electrocardiographic moni-toring and analysis of creatine kinase isoforms. Continuous on-line monitoring of QRS and ST vectors determined reperfusion correctly in 15 of 16 patients and the lack of reperfusion in 4 of 5.60 Early analysis of creatine kinase MM isoforms has shown similar promise.61 Neither method has been tested on a large number of patients.

DEFERRED ADJUNCTIVE CORONARY ANGIOPLASTY Two large studies have compared the strategy of deferred adjunctive angioplasty after myocardial infarction to prevent recurrent ischemia with the strategy of performing coronary angiography and angioplasty for evidence of recurrent ischemia. In the TIMI II trial,62 3,262 patients received rt-PA and were randomized to angiography and prophylactic angioplasty 18 to 48 hours after infarction or to a conserva-tive strategy of reserving angioplasty only for patients with recurrent ischemia. Only 54% of the invasive group under-went angioplasty, as did 13% of the conservative group. No differences were noted in the primary end point of reinfarction or death at 6 weeks of follow-up (6.9% in the invasive group and 7.4% in the conservative group) or the secondary end point of left ventricular ejection fraction. After 1 year of follow-up, rates of mortality and reinfarction (9.4% in the invasive group and 9.8% in the conservative group) were similar in the two groups despite an increased frequency of rehospitalization and coronary arteriography in the conservative group.63-64

The SWIFT (Should We Intervene Following Thrombolysis?) trial65 randomized 800 patients with similar study design but used anistreplase as the thrombolytic agent. After 1 year of follow-up, mortality rates and left ventricular function were similar between the two groups, as in the TIMI II trial. Similar to the results of TIMI II, the conservative group had a greater incidence of recurrent ischemia, as evi-denced by the higher rates of angiography and revascularization during follow-up. Thus, deferred adjunc-tive angioplasty does not seem to decrease mortality substan-tially or to improve left ventricular function when compared with a strategy of angiography and revascularization for spontaneous or exercise-induced ischemia ("watchful wait-ing"). The effect of deferred coronary angiography on the

subsequent need for further cardiac procedures remains un-clear.

CONCLUSION Coronary angioplasty may have a central role in the immedi-ate management of acute myocardial infarction. Although primary coronary angioplasty has not been shown to be more effective than thrombolytic therapy in salvaging myocar-dium, it results in an equivalent amount of myocardial sal-vage and seems to limit the recurrent ischemia that often occurs after reperfusion therapy. Currently, primary coro-nary angioplasty is the treatment of choice in the large group of patients in whom thrombolytic therapy is contraindicated. Primary angioplasty may be particularly helpful in elderly patients, in those who have undergone prior coronary artery bypass grafting, and in those in cardiogenic shock. Routine immediate adjunctive angioplasty after thrombolytic therapy has been well studied and has not been shown to be of substantial benefit. Nonrandomized data, however, suggest that rescue angioplasty may be helpful for patients in whom thrombolytic therapy has failed. Until rapid, sensitive, and specific noninvasive markers of coronary artery patency are available, a sensible approach is to perform angiography immediately in all high-risk patients (patients in whom failed thrombolysis can be expected to cause excess morbidity and mortality). Among the remaining patients who receive thrombolytic therapy, a strategy of angiography for those with spontaneous or exercise-induced ischemia seems to be logical.

ACKNOWLEDGMENT We express gratitude to Charanjit S. Rihai, M.D., and Kent R. Bailey, Ph.D., for the statistical aspects of the meta-analysis in Table 2.

REFERENCES 1. Reimer KA, Lowe JE, Rasmussen MM, Jennings RB. The wavefront

phenomenon of ischemie cell death. 1. Myocardial infarcì size vs duration of coronary occlusion in dogs. Circulation 1977; 56:786-794

2. Reimer KA, Jennings RB. The "wavefront phenomenon" of myocar-dial ischemie cell death. II. Transmural progression of necrosis within the framework of ischemie bed size (myocardium at risk) and collateral flow. Lab Invest 1979;40:633-644

3. De Wood MA, Spores J, Notske R, Mouser LT, Burroughs R, Golden MS, et al. Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction. N Engl J Med 1980; 303:897-902

4. Rentrop P, Blanke H, Karsch KR, Kaiser H, Köstering H, Leitz K. Selective intracoronary thrombolysis in acute myocardial infarction and unstable angina pectoris. Circulation 1981;63:307-317

5. Fletcher AP, Alkjaersig N, Smyrniotis FE, Sherry S. The treatment of patients suffering from early myocardial infarction with massive and prolonged streptokinase therapy. Trans Assoc Am Phys 1958; 71:287-296


6. European Cooperative Study Group for Streptokinase Treatment in Acute Myocardial Infarction. Streptokinase in acute myocardial infarction. N Engl J Med 1979;301:797-802

7. White HD, Norris RM, Brown MA, Takayama M, Maslowski A, Bass NM, et al. Effect of intravenous streptokinase on left ventricu-lar function and early survival after acute myocardial infarction. N Engl J Med 1987;317:850-855

8. I.S.A.M. Study Group. A prospective trial of intravenous streptoki-nase in acute myocardial infarction (I.S.A.M.): mortality, morbidity, andinfarctsizeat21 days. N Engl J Med 1986;314:1465-1471

9. Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI). Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986;1:397-401

10. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988; 2:349-360

11. AIMS Trial Study Group. Long-term effects of intravenous anistreplase in acute myocardial infarction: final report of the AIMS study. Lancet 1990;335:427-431

12. Wilcox RG, von der Lippe G, Olsson CG, Jensen G, Skene AM, Hampton JR (for the ASSET Study Group). Trial of tissue plasmino-gen activator for mortality reduction in acute myocardial infarction: Anglo-Scandinavian Study of Early Thrombolysis (ASSET). Lancet 1988; 2:525-530

13. Grüntzig AR, Senning Â, Siegenthaler WE. Nonoperative dilatation of coronary-artery stenosis: percutaneous transluminal coronary angioplasty. N Engl J Med 1979;301:61-68

14. Swan HJC. Thrombolysis in acute myocardial infarction: treatment of the underlying coronary artery disease [editorial]. Circulation 1982; 66:914-916

15. Meyer J, Merx W, Schmitz H, Erbel R, Kiesslich T, Dörr R, et al. Percutaneous transluminal coronary angioplasty immediately after intracoronary streptolysis of transluminal myocardial infarction. Cir-culation 1982; 66:905-913

16. Hartzler GO, Rutherford BD, McConahay DR, Johnson WL Jr, McCallister BD, Gura GM Jr, et al. Percutaneous transluminal coronary angioplasty with and without thrombolytic therapy for treatment of acute myocardial infarction. Am Heart J 1983; 106:965-973

17. Holmes DR Jr, Smith HC, Vlietstra RE, Nishimura RA, Reeder GS, Bove AA, et al. Percutaneous transluminal coronary angioplasty, alone or in combination with streptokinase therapy, during acute myocardial infarction. Mayo Clin Proc 1985;60:449-456

18. Erbel R, Pop T, Henrichs K-J, von Olshausen K, Schuster CJ, Rupprecht H-J, et al. Percutaneous transluminal coronary angioplasty after thrombolytic therapy: a prospective controlled randomized trial. J Am Coll Cardiol 1986; 8:485-495

19. O'Keefe J Jr, Rutherford BD, McConahay DR, Ligon RW, Johnson WL Jr, Giorgi LV, et al. Early and late results of coronary angioplasty without antecedent thrombolytic therapy for acute myo-cardial infarction. Am J Cardiol 1989;64:1221-1230

20. Brodie BR, Weintraub RA, Stuckey TD, LeBauer J, Katz JD, Kelly TA, et al. Direct angioplasty for acute myocardial infarction: results in candidates and non-candidates for thrombolytic therapy [abstract]. Circulation 1989; 80(Suppl 2):II-624

21. Rothbaum DA, Linnemeier TJ, Landin RJ, Steimetz EF, Hillis JS, Hallam CC, et al. Emergency percutaneous transluminal coronary angioplasty in acute myocardial infarction: a 3 year experience. J Am Coll Cardiol 1987; 10:264-272

22. Kimura T, Nosaka H, Ueno K, Nobuyoshi M. Role of coronary angioplasty in acute myocardial infarction [abstract]. Circulation 1986; 74(Suppl 2):II-22

23. Marco J, Caster L; Szatmary L, Fajadet J. Emergency percutaneous transluminal coronary angioplasty without thrombolysis is initial therapy in acute myocardial infarction. Int J Cardiol 1987; 15:55-63

24. O'Neill WW, Brodie B, Knopf W, Ivanhoe R, O'Keefe J, Taylor G, et al. Initial report of the Primary Angioplasty Revascularization

(PAR) Multicenter Registry [abstract]. Circulation 1991; 84(Suppl 2):II-536

25. Kahn JK, Rutherford BD, McConahay DR, Johnson WL, Giorgi LV, Shimshak TM, et al. Catheterization laboratory events and hospital outcome with direct angioplasty for acute myocardial infarction. Circulation 1990; 82:1910-1915

26. Grines C, Califf R, Brodie B, Ivanhoe R, Knopf W, Taylor G, et al. Bleeding complications associated with direct angioplasty for acute myocardial infarction: report of Primary Angioplasty Research (PAR) group [abstract]. J Am Coll Cardiol 1992; 19(Suppl A):137A

27. Grines CL, Browne KF, Marco J, Rothbaum D, Stone G, O'Keefe J, et al. A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction. N Engl J Med 1993; 328:673-679

28. Simonton CA, Mark DB, Hinohara T, Rendali DS, Phillips HR, Peter RH, et al. Late restenosis after emergent coronary angioplasty for acute myocardial infarction: comparison with elective coronary angioplasty. J Am Coll Cardiol 1988;11:698-705

29. Tison E, Bommeaux A, Lablanche JM, Bauters C, Leroy F, Bertrand ME. Long term risk/benefit of PTCA of infarct related vessel [ab-stract]. J Am Coll Cardiol 1991; 17(Suppl A):266A

30. Lee L, Erbel R, Brown TM, Laufer N, Meyer J, O'Neill WW. Multicenter registry of angioplasty therapy of cardiogenic shock: initial and long-term survival. J Am Coll Cardiol 1991; 17:599-603

31. Hibbard MD, Holmes DR Jr, Bailey KR, Reeder GS, Bresnahan JF, Gersh BJ. Percutaneous transluminal coronary angioplasty in pa-tients with cardiogenic shock. J Am Coll Cardiol 1992; 19:639-646

32. Cragg DR, Friedman HZ, Bonema JD, Jaiyesimi IA, Ramos RG, Timmis GC, et al. Outcome of patients with acute myocardial infarction who are ineligible for thrombolytic therapy. Ann Intem Med 1991; 115:173-177

33. Ellis SC, O'Neill WW, Bates ER, Walton JA, Nabel EG, Topol EJ. Coronary angioplasty as primary therapy for acute myocardial infarction 6 to 48 hours after symptom onset: report of an initial experience. J Am Coll Cardiol 1989;13:1122-1126

34. Bedotto JB, Kahn JK, Rutherford BD, McConahay DR, Giorgi LV, Johnson WL, et al. Failed direct coronary angioplasty for acute myocardial infarction: in-hospital outcome and predictors of death. J Am Coll Cardiol 1993; 22:690-694

35. Lee TC, Laramee LA, Rutherford BD, McConahay DR, Johnson WL Jr, Giorgi LV, et al. Emergency percutaneous transluminal coronary angioplasty for acute myocardial infarction in patients 70 years of age and older. Am J Cardiol 1990;66:663-667

36. Holland KJ, O'Neill WW, Bates ER, Pitt B, Topol EJ. Emergency percutaneous transluminal coronary angioplasty during acute myo-cardial infarction for patients more than 70 years of age. Am J Cardiol 1989;63:399-403

37. Kahn JK, Rutherford BD, McConahay DR, Johnson W, Giorgi LV, Ligon R, et al. Usefulness of angioplasty during acute myocardial infarction in patients with prior coronary artery bypass grafting. Am J Cardiol 1990;65:698-702

38. O'Neill W, Timmis GC, Bourdillon PD, Lai P, Ganghadarhan V, Walton J Jr, et al. A prospective randomized clinical trial of intracoronary streptokinase versus coronary angioplasty for acute myocardial infarction. N Engl J Med 1986;314:812-818

39. Behrenbeck T, Pellikka PA, Huber KC, Bresnahan JF, Gersh BJ, Gibbons RJ. Primary angioplasty in myocardial infarction: assess-ment of improved myocardial perfusion with technetium-99m isonitrile. J Am Coll Cardiol 1991;17:365-372

40. Christian TF, Schwartz RS, Gibbons RJ. Determinants of infarct size in reperfusion therapy for acute myocardial infarction. Circulation 1992; 86:81-90

41. Gibbons RJ, Holmes DR, Reeder GS, Bailey KR, Hopfenspirger MR, Gersh BJ (for the Mayo Coronary Care Unit and Catheterization Laboratory Groups). Immediate angioplasty compared with the ad-ministration of a thrombolytic agent followed by conservative treat-ment for myocardial infarction. N Engl J Med 1993;328:685-691


42. Zijlstra F, de Boer MJ, Hoorntje JCA, Reiffers S, Reiber JHC, Suryapranata H. A comparison of immediate coronary angioplasty with intravenous streptokinase in acute myocardial infarction. N Engl J Med 1993; 328:680-684

43. TIMI Research Group. Immediate vs delayed catheterization and angioplasty following thrombolytic therapy for acute myocardial infarction: TIMI II A results. JAMA 1988;260:2849-2858

44. Karlson BW, Herlitz J, Edvardsson N, Emanuelsson H, Sjölin M, Hjalmarson A. Eligibility for intravenous thrombolysis in suspected acute myocardial infarction. Circulation 1990;82:1140-1146

45. Simoons ML, Arnold AER, Betriu A, deBono DP, Col J, Dougherty FC, et al. Thrombolysis with tissue plasminogen activator in acute myocardial infarction: no additional benefit from immediate percuta-neous coronary angioplasty. Lancet 1988;1:197-203

46. Topol EJ, Califf RM, George BS, Kereiakes DJ, Abbottsmith CW, Candela RJ, et al. A randomized trial of immediate versus delayed elective angioplasty after intravenous tissue plasminogen activator in acute myocardial infarction. N Engl J Med 1987;317:581-588

47. Waller BF, Rothbaum DA, Pinkerton CA, Cowley MJ, Linnemeier TJ, Orr C, et al. Status of the myocardium and infarct-related coronary artery in 19 necropsy patients with acute recanalization using pharmacologie (streptokinase, r-tissue plasminogen activator), mechanical (percutaneous transluminal coronary angioplasty) or combined types of reperfusion therapy. J Am Coll Cardiol 1987; 9:785-801

48. Dalen JE. Intravenous thrombolytic therapy in acute myocardial infarction—six month followup: the NHLBI Thrombolysis in Myo-cardial Infarction (TIMI) trial [abstract]. J Am Coll Cardiol 1987; 9(Suppl A):60A

49. 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;312:1073-1078

50. Fung AY, Lai P, Topol EJ, Bates ER, Bourdillon PDV, Walton JA, et al. Value of percutaneous transluminal coronary angioplasty after unsuccessful intravenous streptokinase therapy in acute myocardial infarction. Am J Cardiol 1986;58:686-691

51. Holmes DR Jr, Gersh BJ, Bailey KR, Reeder GS, Bresnahan JF, Bresnahan DR, et al. Emergency "rescue" percutaneous transluminal coronary angioplasty after failed thrombolysis with streptokinase: early and late results. Circulation 1990; 81(Suppl 4):IV51-IV56

52. Topol EJ, Califf RM, George BS, Kereiakes DJ, Rothbaum D, Can-dela RJ, et al. Coronary arterial thrombolysis with combined infusion of recombinant tissue-type plasminogen activator and urokinase in patients with acute myocardial infarction. Circulation 1988; 77:1100-1107

53. GUSTO Investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl JMed 1993;329:673-682

54. Califf RM, Topol EJ, Stack RS, Ellis SG, George BS, Kereiakes DJ, et al. 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;83:1543-1556

55. Gacioch GM, Topol EJ. Sudden paradoxic clinical deterioration during angioplasty of the occluded right coronary artery in acute myocardial infarction. J Am Coll Cardiol 1989;14:1202-1209

56. Abbottsmith CW, Topol EJ, George BS, Stack RS, Kereiakes DJ, Candela RJ, 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; 16:770-778

57. Califf RM, O'Neill W, Stack RS, Aronson L, Mark DB, Mantell S, et al. Failure of simple clinical measurements to predict perfusion status after intravenous thrombolysis. Ann Intern Med 1988; 108:658-662

58. Hohnloser SH, Zabel M, Kasper W, Meinertz T, Just H. Assessment of coronary artery patency after thrombolytic therapy: accurate prediction utilizing the combined analysis of three noninvasive mark-ers. J Am Coll Cardiol 1991;18:44-49

59. Shah PK, Cercek B, Lew AS, Ganz W. Angiographie validation of bedside markers of reperfusion. J Am Coll Cardiol 1993;21:55-61

60. Dellborg M, Swedberg K (for the TEAHAT study group). Dynamic QRS-complex and ST-segment vectorcardiographic monitoring in acute myocardial infarction [abstract]. Circulation 1989; 80(Suppl 2):II-355

61. Seacord LM, Abendschein DR, Nohara R, Hartzler G, Sobel BE, Jaffe AS. Detection of reperfusion within 1 hour after coronary recanalisation by analysis of isoforms of the MM creatine kinase isoenzyme in plasma. Fibrinolysis 1988;2:151-156

62. TIMI Study Group. Comparison of invasive and conservative strate-gies after treatment with intravenous tissue plasminogen activator in acute myocardial infarction: results of the Thrombolysis in Myocar-dial Infarction (TIMI) Phase II Trial. N Engl JMed 1989; 320:618-627

63. Williams DO, Braunwald E, Knatterud G, Babb J, Bresnahan J, Greenberg MA, et al. One-year results of the Thrombolysis in Myocardial Infarction (TIMI) phase II trial. Circulation 1992; 85:533-542

64. Rogers WJ, Babb JD, Bairn DS, Chesebro JH, Gore JM, Roberts R, et al. Selective versus routine predischarge coronary arteriography after therapy with recombinant tissue-type plasminogen activator, heparin and aspirin for acute myocardial infarction. J Am Coll Cardiol 1991; 17:1007-1016

65. SWIFT (Should We Intervene Following Thrombolysis?) Trial Study Group. SWIFT trial of delayed elective intervention v conservative treatment after thrombolysis with anistreplase in acute myocardial infarction. BMJ 1991;302:555-560

Documents

Coronary Angioplasty in Acute Myocardial Infarction: Primary, Immediate Adjunctive, Rescue, or Deferred Adjunctive Approach?