Acute myocardial infarction treated with intracoronary streptokinase: A report of the society for cardiac angiography

APRIL 1, 1985

The American

Journal

of CARDIO,LOGY@ VOLUME 55 NUMBER 8

CORONARY HEART DISEASE

Acute Myocardial Infarction Treated with lntracoronary Streptokinase: A Report of the Society for Cardiac Angiography * J. WARD KENNEDY, MD, GOFFREDO G. GENSINI, MD, GERALD C. TIMMIS, MD, and CHARLES MAYNARD,

MA

The Society for Cardiac Angiography maintains a regtstry of intracoronary streptokinase therapy (IC-SK) in pagents with acute myocardial infarction. Between July 1981 and August 1984,1,029 patients were entered into the registry. The baseline and clinical charactertstks of patients were determined, the early results of therapy were evaluated, and baseline characteristics of those in whom reperfusion was achieved were compared with those in whom it was not. Multivariate discriminant analysis was used to kfentify the predictors of reperfusion and hospital mortality. The overall rate of reperfusion was 71.2 %. Reperfusion was positively associated with hypotension, absence of cardtogenlc shock and

early treatment. The hospital mortality rate for all patients was 8.2% and was higher for women and the elderly. The hospital mortality was significantly lower among patients in whom reperfusion was achieved compared with those in whom it was not (5.5% vs 14.7%, p
During the last 5 years there has been a striking change in the early management of acute myocardial infarction

(AMI) as a result of several important clinical and laboratory investigations. During the mid-1970s there were efforts to limit infarct size with the use of various drugs. Although these interventions may have had a sound physiologic basis and been of some benefit, they were not successful in reducing the mortality rate of AMI.’ At the same time, experimental studies in animals clearly demonstrated that coronary reperfusion after varying periods of coronary occlusion resulted in salvage of ischemic myocardium.2,3 In a few clinical centers, coronary artery reperfusion using coronary artery by-

*l3egMtycomnlltteeforthesocletyforcerdicAnglogaphy:Goffredo

Gemini, MD,chakmen;Mahdi AWassam, MD,JosephR.Dorchak,M>, Robart M. @aen, MD, John Hirshfeld. MD, Sarah Johnson, MD. J. Ward Kennedy, MD, Kenneth M. Kent, MD, Stephen B. King, MD, Ronald J. Krone, MD, Gcrdon A. Logan, MD, Michael D. Moscovich, MD, Richard K. Myier, MD, Thomas J. Noto, MD, Sven Paulin, MD, August0 Pichard, MD, Fred Schoonmaker, MD, Gerald C. Timmis, MD, and George W. Vetrovec, MD. Manuscript received and accepted Janwy 7,1985. Address for reprints: Society for Cardiac Angiography, 9500 Euclid Avenue, Cleveland, Ohio 44106. 871

872

INFARCTION

TABLE I

TREATED

WITH STREPTOKINASE

Variables Used in Linear Discriminant

Analysis

2:

Time from onset of symptoms to hospital admission Time from onset of pain to streptokinase therapy History of myocardial infarction Prior bypass surgery History of congestive heart failure Ongoing chest pain Hemodynamically stable Hypotension Cardiogenic shock Direct-current cardioversion Moribund Balloon pump Number of diseased vessels Location of thrombus Reperk&on Death in hospital

pass surgery within the first 6 hours after the onset of AM1 resulted in unexpectedly low mortality and apparent improvement in long-term survival.4*5For many years the role of coronary artery thrombosis in the pathogenesis of AM1 was controversial. This controversy ended when early coronary arteriography in patients with AM1 almost always revealed coronary artery thrombus.6 In this scientific climate, the initial reports of successful thrombolysis with the use of intracoronary streptokinase (IC-SK) in patients with AM1718were quickly followed by a number of reports describing the results of the new therapy.s-12 More recently, additional reports about the results of IC/SK have been published.l3-l6 To collect additional information about thrombolytic therapy, the Society for Cardiac Angiography began an intracoronary streptokinase registry. Between July 1,1981, and August 1,1984,1,029 patients were registered by 35 laboratories. In this report, we present the clinical and hemodynamic characteristics of these patients, the efficacy of thrombolytic therapy relative to coronary reperfusion, and the hospital morbidity and mortality rates. There are no results from control patients with which to compare these results. We therefore compare the patients in whom IC-SK resulted in reperfusion with those in whom the therapy was unsuccessful. In making these comparisons, we do not assume that patients in whom reperfusion is not achieved have the same characteristics as an untreated control group. We recognize the limitations of observational, uncontrolled studies in the evaluation of new forms of therapy. We also believe that it is difficult or impossible to study high-risk subgroups of patients with controlled, randomized trials. Because there may be important differences in the risk and benefit of IC-SK therapy for various subgroups of patients, a registry that includes enough patients in these subgroups may contribute important information that may not be available from other sources. Thus, we believe that this multiinstitutional registry study will complement information obtained from controlled trials. Methods This streptokinase registry is a voluntary activity of the Society in which members report clinical, angiographic and short-term outcome information on patients with AMI who

TABLE II

Patient Enrollment in Society for Cardiac Angiography Streptokinase Registry

Laboratory St. Vincent’s, New York, NY Straub Clinic, Honolulu, HI Vanderbilt University, Nashville, TN Lancaster General, Lancaster, PA St. Joseph’s, Syracuse, NY Mt. Sinai, Miami, FL St. Luke’s, New York, NY Burgess Hospital, Kalamazoo, Ml St. Louis University, St. Louis, MO St. Luke’s, Denver, CO Mercy Hospital, Charlotte, NC Wm. Beaumont, Royal Oak, MI Crouse Irving Hospital, Syracuse, NY Emery University Hospital, Atlanta, GA U.S.C. Medical Center, Los Angeles, CA Med. COILof Virginia, Richmond, VA Naval Hospital, San Diego, CA St. Joseph’s, Burbank, CA Lovelace Clinic, Albuquerque, NM Bryan Memorial Hospital, Lincoln, NE Toranomon, Tokyo Bridgeport Hosp., Bridgeport, CT 13 other institutions Total no. of pts

No. of Pts Enrolled 120 34

1,029

have been treated with IC-SK. Participating laboratories agreed to register consecutive patients in a prospective manner. Because some laboratories had acquired experience with thrombolytic therapy before July 1981, these laboratories

wereencouragedto enter patients in a retrospectivemanner so as to include all patients previously treated in their laboratories. Data collection forms were developed and distributed. They were submitted to a central data analysis laboratory, where the information was checked for consistency and completeness

and entered into a computer data bank. Data collected included age,sex, prior myocardial infarction, history of congestiveheart failure and prior coronaryartery bypasssurgery. The presence or absence of chest pain immediately before cardiac catheterization was recorded. The patient’s hemodynamic status was categorized as stable, hypotensive (blood pressure less than 90 mm Hg systolic), or cardiogenic shock. The cardiogenic shock syndrome was not rigidly defined. Patients in pulmonary edema but not in shock and those in a moribund state were identified. The use of precatheteriza-

tion precordial shockfor the treatment of ventricular fibrillation and ventricular tachycardia and the use of intraaortic balloon pump were also noted. The location of AM1 based on the electrocardiographic and angiographic findings was recorded. Each patient was classified as having either an anterior or inferior infarction. Lateral infarctions were classified as anterior and posterior infarctions were classified as inferior. From the coronary arteriograms, patients were classified as having l-, 2- or 3-vessel,or left main coronary artery disease. Disease was considered present if there was at least 50?6diameter narrowing of a major coronary artery. Most patients received intracoronary nitroglycerin before the administration of streptokinase, and the result of this therapy, designed to detect the presence of coronary artery spasm, was recorded. The use of a guidewire for thrombus perforation was noted. Reperfusion after IC-SK therapy was recorded as present or absent and not graded as partial or complete. Evidence of reocclusion during hospitalization was recorded. The patient’s clinical status at the time of hospital discharge was reported and included death, the development of Q-wave

April

TABLE III

1, lY83

1Ht

AMtKlGAN

JUUKNAL

W

C;AKUIULUtiY

volume

33

IIS

Clinical Status Before Catheterization

?ime to hosp (min) Time to angio (min) lschemic pain Hemodynamic status Stable Hypotensive (SBP <90) Cardiogenic shock Pulmonary edema Defibrillation Moribund Balloon pump

Total

AMI

MI

p Value

1,029 119f201 240 f 413 95.3%

467 124f250 241 f 273 96.1%

551 114 f 236 238 f 504 94.7%

0.009 NS

86.4% 10.9%

85.4% 10.6% 5.1% 4.3% 7.5% 3.2% 1.7%

87.4% 11.2% 3.7% 1.1% 7.4% 0.5% 0.9%

NS

ii::7 0.3 7.4% 1.9% 1.3%

AMI = anterior myocardial infarction; angio = angiography; hosp = hospitalization; myocardial infarction; NS = not significant; SBP = systolic blood pressure (mm Hg).

infarction, presence of stable or unstable angina and the use of anticoagulant and antiplatelet agents. Patients who underwent surgical revascularization or balloon dilatation of the coronary artery after streptokinase therapy were identified. Finally, the complications of therapy were recorded. Becausemultiple factors determine if a vessel will reperfuse with IC-SK, or if the patient will survive an AMI, we have performed multivariate discriminant analysis of the predictors of reperfusion and mortality. This analysis has been used with 3 groups of patients: Group Z-all patients. This group includes the 1,029 patients for whom vital status was known and the 1,011patients for whom reperfusion status was known. Group II-patients with anterior infarcts (n = 467). Group III-patients with inferior infarcts (n = 544). Statistical methods: Patient characteristics were screened univariately using the chi-square statistic for discrete variables and the t test for continuous variables. Multivariate statistical methods were used to identify baseline factors that are important in determining reperfusion and hospital mortality. Stepwise linear digcriminant analysis was used to distinguish the group that survived from the group that died and the group in which reperfusion was achieved from the group in which it was not. In this study, variables related to patient cardiac history, time of treatment, clinical status before cardiac catheterization and coronary anatomy were used to identify the predictors of reperfusion and mortality (Table I). Linear discriminant analysis was used to select the variables that best distinguished the 2 groups of interest.lT The principle of linear discriminant analysis is to select the combination of variables which most completely separatesthe two groups. The process is carried out in a stepwise manner so that the relative importance of each variable selected for the model is identified. The processstops when the remaining, unselected variables do not add significant predictive power to the model (p >0.05). The relative importance of each variable selected is indicated by the F statistic. Variables with F value 14.0 (p <0.05) are included in this report. Results

During the period July 1981 through August 1,1984, 1,029 patients were entered into the registry. Thirty-five catheterization laboratories enrolled 1 to 208 patients (Table II). There were 824 men and 205 women, mean age 5’7 f 10 years. Of the 1,029 patients, 17.8% had a history of AM1 and 3.1% had previous coronary artery bypass surgery. The average time from onset of symptoms of AM1 to hospitalization was 119 f 201 minutes

Ii:

E 0.002 0% NS IMI = inferior

and the average time from symptoms to the onset of therapy was 240 f 413 minutes. Table III is a list of the precatheterization status (by location of infarction) of the patients entered into this registry. All but 5% of the patients were having ischemic pain at the time they went to the catheterization laboratory. Most of the patients (86.4%)were hemodynamicahy stable, 10.9%were hypotensive and 4.4%of them were in cardiogenic shock. Defibrillation was required before catheterization in 7.4% of patients. Only a few patients had pulmonary edema, were moribund or were receiving intraaortic balloon pump treatment. There were significantly more patients with inferior than with anterior AM1 (p = 0.009). Comparison of patients with anterior infarction to those with inferior infarction indicated few differences in baseline clinical characteristics. Remarkably, the incidence of hypotension was similar in both groups. Although infrequent in both groups, pulmonary edema was more common in those with anterior AM1 than in those with inferior AMI, 4.3% vs 1.1% (p = 0.061). Reperfusion occurred in 71.2%of the patients (Table IV). The rate of reperfusion was not different between men and women or between those who were hemodynamically stable vs those who were unstable. Reperfusion was less likely if the patient was not having chest pain (p = 0.0004), was in cardiogenic shock (p
INFARCTIONTREATEDWITH STREPTOKINASE

074

TABLE IV

Hospital Mortality

All Men Women Ag~;tb) 60-69 70-74 275 Stable i-l;p$tsion

l

Edema’ Cardioversion’ [deebrillation) RCA gher l

n

% Reperfused

Total

Reperfused

Not Reperfused

p Value

1,029 624 205

71.2% 73.3% 69.6%

8.2% 7.1% 12.7%

5.5% 5.1% 7.0%

14.7% 11.6% 25.8%

<0.0001 0.001 0.0002

593 309 3; 664 107

73.9% 73.1% 63.1% 65.6% 72.8% 84.8%

2

EF. 0

3.2% 12.0% 18.2% 37.5% 5.1% 5.6% 66.7% 38.2 %

2.5% 6.8% 16.3% 28.6% 3.6% 4.5% 42.1% 31.8%

5.2% 25.9% 21.4% 54.5% 6.1% 12.5% 84.0% 54.5%

4:: 424 127 19

:t : 7 75:3; 63.8% 72.2%

6.3% 12.1% 4.0% 7.9% 10.5%

9.3% 6.4% 2.9% 2.5% 15.4%

5.9% 21.2% 6.8% 17.4% 0.0%


Shock patients not included. = left CirCUt?‘tf~eX artery; LAD = left anterior descending coronary artery; NS = not significant; RCA = right coronary artery.

CX

TABLE V

Patient Characteristics

by Status of Reperfusion’ n

Total

57 f 10 1,014 Age04 240 f 413 928 Time to treatment (min) Duration of infusion (min) 57 f 23 835 235 f 102 862 Total dose (1,000 IU) LVEDP before (mm Hg) 21.1 f 8.4 638 18.2% 1,011 % to CABG % to PTCA 7.3% 1,011 Reperfusion status could not be determined for 18 patients. CASG = COTCWINY arterv bvoass sumerv: LVEDP = left ventricutar enddiitolic coronary angioplasty. - -’

Reperfusion

No Reperfusion

57f 10 209 f 137 57 f 22 234 f 103 21.6 f 6.3 21.1% 8.5%

57f 11 331 f 780 57 f 27 232 f 101 19.8 f 8.5 10.4% 4.3%

p Value ON:01 Ii: 0.017 <0.0001 0.024

l

and were more likely to have subsequent coronary artery bypass surgery (21.1% vs 10.4%, p
pressure; NS = not significant; PTCA = percutaneous transluminat

among patients 60 to 69 years of age. For the 309 patients between 60 and 69 years of age, the reperfusion rate was 73.1%, and those in whom reperfusion was successful had a mortality rate of 6.8%, whereas those in whom reperfusion failed had a mortality of 25.9% (p
April 1.1985

indication of its relative importance (Table VI). Group I includes all 789 patients for whom all of the 18 variables used in the analysis were available. In group I, shock, age, location of infarction and history of infarction are related to hospital mortality; and ongoing chest pain, shock, hypotension, time to angiography and history of congestive heart failure are related to reperfusion. Group II includes patients with anterior AMI. In this group only shock and age, and shock and time to angiography are related to hospital mortality and reperfusion, respectively. Group III includes the patients with inferior AMI. In these patients, shock is not related to mortality or reperfusion as it is in groups I and II, and the F values for the predictors of mortality are much lower than those in groups I and II. Discussion Limitations of the registry: In this report, using data from a registry, we have attempted to define the efficacy of IC-SK for the treatment of patients with AMI. The large number of patients (1,029) permits the analysis of various important subgroups of patients. The registry has limitations: (1) It contains no untreated, control patients with which to compare the results achieved in treated patients. (2) Patients were not followed up beyond hospital discharge. (3) Incomplete data collection reduces the numbers of patients available for multivariate analysis of hospital mortality and reperfusion. The efficacy of IC-SK therapy must finally be determined from the results of large randomized trials. Randomized trials, however, are restricted to populations in whom randomization is acceptable to both patients and physicians. This makes the inclusion of high-risk patients, as those in shock, difficult if not impossible. Determinants of reperfusion: We have examined the information available in this registry to determine the factors that influence the likelihood of coronary artery reperfusion. Univariately, the most important

THE AMERICAN

TABLE VI

JOURNAL

OF GARUIOLwtiY

volume

33

(115

Results of Linear Discriminant Analysis

Group I-All Mortality (n = 789) Variable Shock Age Location of MI History of MI

Patients Reperfusion (n = 789)

F at Entry

Variable

F at Entry

186.7 112.9 82.5 64.7

Ongoing Pain Shock Hypotension Time to Angiography History of CHF

13.9 13.0 10.8 9.5 8.8

Group II-Anterior Ml Mortality (n = 358) Reperfusion (n = 358) Variable Shock Age

F at Entry

Variable

F at Entry

165.5 103.6

Shock Time to Angiography

14.7 9.9

Group Ill-Inferior MI Mortality (n = 431) Reperfusion (n = 431) Variable

F at Entry

Variable

F at Entry

23.7 19.7 15.5

Ongoing Pain Balloon Pump Hypotension

8.9 7.2 6.6

Balloon Pump History of MI Age

CHF = congestive heart failure; Ml = myocardial infarction.

factor in reperfusion is the time from the onset of chest pain to the onset of therapy; in fact, there was a mean difference of 88 minutes between those in whom reperfusion was achieved and those in whom it was not. Others have observed a relation between time and reperfusion.18 The left ventricular end-diastolic pressure measured before streptokinase infusion was also related to reperfusion in that the group of patients in whom reperfusion failed had a slightly lower pressure. However, the relation between left ventricular end-diastolic pressure and reperfusion is weak, and we cannot explain it in physiologic terms. There is also a much lower likelihood of reperfusion in patients in cardiogenic shock. This may be a result of the early death of some of these patients before streptokinase infusion could be

60 55 50 t

4s

2

40

G

3s

FIGURE 1. Relation of age, reperfusion and mortality

z

rate. NR = not reperfused; NS = not significant: R = reperfused.

2

30 Bs

Ll

z z

I

P-NS

r 76 1111 za

20 15 P-NS

10 5 R

NR 20-59

R

NR 60-60

R

NR

70+

AGE

876

INFARCTION

TREATED

WITH STREPTOKINASE

successful, but the data do not allow us to evaluate this hypothesis. The presence of ongoing chest pain is also related to reperfusion in that reperfusion is more likely in patients with continuing pain. This variable probably interacts with time to angiography, because in the multivariate analysis only ongoing pain enters the model. Finally, reperfusion was more likely to be successful in hypotensive patients who were not in shock (84.8%, p = 0.007) than in other patients in this study. Patients in cardiogenic shock were the least likely to achieve reperfusion (43.2%). The reason for improved reperfusion in hypotensive patients is not clear. Hypotensive patients who were not in shock were treated earlier (187 f 96 minutes) than okher patients who were not in shock (244 f 436 minutes), but this difference was not statistically significant (p = 0.20). Reperfusion and mortality: Overall, reperfusion is associated with a marked reduction in hospital mortality (5.5% vs 14.7%) for the entire population of patients. This reduction in mortality is greater for women (7% ~~25.8%)than for men (5.1%vs 11.6%),but it is also significantly related to the patient’s age. The decrease in mortality is greatest for those in the 60- to 69-year age group. In classifying patients as stable, hypotensive or in cardiogenic shock, it becomes clear that those who benefit most from coronary artery reperfusion have the most impaired hemodynamic state. On the other hand, those in whom reperfusion is not achieved do not appear to have been injured from therapy, because they have a hospital mortality rate similar to patients receiving conventional therapy.igJO Reperfusion is least likely to occur in patients who are in shock. Occasionally, this may be a result of early death of the patient before streptokinase therapy has had time to be effective, or it may be a result of interruption of therapy by acute deterioration of the patient’s hemodynamic status or by superimposed ventricular arrhythmias. The absence of information with respect to these factors does not permit an analysis of their roles in explaining the reduced likelihood of reperfusion in patients in shock. We also attempted to assessthe impact of pulmonary edema and direct-current cardioversion on hospital mortality. Both of these clinical events are frequently associatedwith cardiogenic shock. Since there is interest in the importance of pulmonary edema and cardiac arrhythmias requiring direct-current cardioversion in patients without shock, these patients have been analyzed separately. Only 25 patients in our study had pulmonary edema, and the mortality is high in both reperfused and nonreperfused patients (31.8%vs 54.5%, difference not significant). In the 72 patients who required cardioversion, the mortality tended to be higher among patients in whom reperfusion was achieved than among those in whom it was not (9.3% vs 5.9%, difference not significant). Others have reported a reduction in hospital mortality in patients receiving E-SK therapy. In a registry of 224 patients, Weinstein21 reported a hospital mortality of 4.5% in 176 patients in whom reperfusion was achieved and an 18%mortality in 48 patients in whom

it was not. There was 14.6%mortality in a group of 178 patients who received conventional coronary care. Timmis et a122reported a 4.7% mortality in 84 patients who received IC-SK and an 11.8% mortality in a consecutively enrolled group of patients who received conventional therapy. Coronary anatomy and mortality: The location of the occluded vessel resulting in AMI, or what is often referred to as the “infarct vessel,” is an important determinant of mortality. Because the highest mortality rate is present in patients with left anterior descending coronary artery thrombosis, it is not surprising that the benefits of reperfusion are greatest in this group (8.4% vs 21.2%). For patients with right coronary artery occlusions, mortality in the patients in whom reperfusion was not achieved is 2.3 times higher than that in the patients in whom it was, but this difference is not statistically significant. Finally, patients with circumflex occlusions in whom reperfusion was not achieved had a 7 times higher mortality compared with those in whom it was (2.5% vs 17.4%). This very large difference in hospital mortality in this subgroup is unexpected, and the reasons for it are not clear. Finally, we are encouraged by the relatively low incidence of serious complications in these patients. The complications in this study are similar in type and frequency to those that occurred in a large randomized study13 and lower than those reported from another registry.21 In the randomized trial, serious arrhythmia was the most frequent complication, as in this study, and had a similar incidence in treatment and control patients. Bleeding, which occurred in only 1.3%,was less often reported in this registry. Death is not included as a procedural complication in this report because of the difficulty in determining whether death was a result of AMI, the catheterization and angiographic procedure, streptokinase therapy or reperfusion. In conclusion, this study provides additional information about the efficacy of coronary reperfusion in patients with AMI. Reperfusion was accomplished in 71.2% of 1,029 patients, and when it occurred it was associated with a low mortality rate. The patients who have the greatest benefit from reperfusion included those at increased risk, including women, patients with cardiogenic shock and those with left anterior descending and circumflex coronary artery thrombosis. Although the mortality is reduced in all age groups with coronary reperfusion, this difference is only significant in those patients between ages 60 and 69 years. By multivariate analysis of baseline clinical and hemodynamic variables, we have shown that although hospital mortality is related to the severity of the patient’s condition before treatment, success of reperfusion is only weakly related to baseline variables, and the presence of hypotension is unexpectedly a predictor of successful reperfusion. Most randomized studies, clinical reports from single institutions and multi-institutional registry studies indicate that reperfusion is associated with low hospital mortality for patients with AMI. This large registry study confirms these findings and further identifies

April 1.1965

subgroups of patients who are most likely to benefit from coronary reperfusion. Intracoronary thrombolytic therapy is cumbersome and difficult to apply early in the course of AMI. High-dose, short-term intravenous infusion of streptokinase or new thrombolytic agents such as tissue-type plasminogen activator may soon provide an intravenous alternative to IC-SK therapy.23-27 The results of this trial indicate reperfusion is associated with a large reduction in overall hospital mortality from AMI, while those in whom reperfusion fails do not benefit. Early recognition of failure to reperfuse and alternate therapy with percutaneous transluminal coronary angioplasty or revascularization surgery may be the best course for these patients. If this is an effective strategy, intravenous treatment must be followed by rapid assessment of the presence and adequacy of coronary reperfusion. Although noninvasive methods may be used for this purpose, immediate coronary angiography and urgent angioplasty may be the best approach for high-risk patients. References 1. international Collaborative

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2. Constantinl C, Corday E, Lang TW, Meerbaum S, Brasch J, Kaf&m l., Rubbm S, Gofd H, Osher J. Revascularization after 3 hours of coronary arterial occlusion: effects on regional cardiac metabolic function and Infarct size. Am J Cardiol 1975;36:252-284. 3. Relmer KA, Lowe JE, Rasmussen MM, Jennlnge RB. The wavefront phsnomenon of ischemic cell death. I. fdvocardial infarct size vs duration of coronary occlusion in dogs. Circulatioh 1977;58:786-794.

4. DeWood MA, Spores J, Notske RN, Lang HT, Shiekls JP, Sfmpron CS, Rudy LW, Grunwakl R. Medical and surgical management of myocardial infarction.

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5. Cheanvechai C, Effler DB, Loop FD, Groves LK, Sheldon WC, Rezaul M, Sones FM. Emergency myocardiai revascularization. Am J Cardiol 1973; 32:901-908.

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8. Rentrop KP, Blanke H, Karsch KR, Kreuzer H. initial experience

with transluminal recanalizatfon of the recentfy occluded infarct&ted wronary arterf In acute mvocardial infarction: comoarison wfth wnventiirnallv treated patients. Ciin Caidioi 1979;2:92-105. ’

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12. Reduto LA, Freund GC, Gaeta JM, Smelling RW, Lewfs B, Gould KL. Coronary artery reperfusion in acute myocardii infarction: beneficiii effects of intracoronary streptokinase of left ventiicufar safvage and performance. Am Heart J 1981;102:1168-1177. 13. Kennedy JW, Rltchle JL, Davis KB, Fritz JK. Western Washington randomized triii of intracoronary streptokinase in acute myocardlai infarction. N Engl J Med 1983;309:1477-1481.

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with tissue-type

plasminogen

activator.

27. Van de Werl F, Bermm SR, Fox KAA, de Geest H, Hoyng CF, Sobel BE, Collen D. Coronary thrombolysis with intravenously adiniiristered human tissue-tvoe

olasminooen

activator

oroduced

bv recombinant

DNA tech-