533
One-Year Results of the Thrombolysis in
Myocardial Infarction Investigation (TIMI)
Phase II Trial
David 0. Williams, MD; Eugene Braunwald, MD; Genell Knatterud, MD;
Joseph Babb, MD; John Bresnahan, MD; Mark A. Greenberg, MD; Albert Raizner, MD;
Alan Wasserman, MD; Thomas Robertson, MD; Richard Ross, MSc; and TIMI Investigators
Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017
Background. The Thrombolysis in Myocardial Infarction (TIMI) Phase II Trial randomized
3,339 patients to either an invasive (INV, n = 1,681) or a conservative (CON, n = 1,658) strategy
after intravenous recombinant tissue-type plasminogen activator (rt-PA) for acute myocardial
infarction.
Methods and Results. The patients assigned to the INV strategy routinely underwent cardiac
catheterization, and when anatomically appropriate, percutaneous transluminal coronary
angioplasty (PTCA) or coronary artery bypass grafting 18-48 hours after infarction. CON
patients had these procedures only in response to the occurrence of spontaneous or provoked
ischemia. One-year follow-up data are available in 3,316 patients (99.3%). The primary trial
end point, death and nonfatal reinfarction, occurred in 14.7% of INV patients and in 15.2% of
CON patients (p=NS). When analyzed individually, there was no difference (p=NS) in death
(INV, 6.9%; CON, 7.4%) or recurrent infarction (INV, 9.4%; CON, 9.8%) between the two
groups. Anginal status at 1 year was also similar. Cardiac catheterization and PTCA were
performed more often in INV (98.0% and 61.2%, respectively) compared with CON (45.2% and
20.5%, respectively) patients. At 1 year, the cumulative number of patients who underwent
coronary bypass surgery (INV, 17.5%; CON, 17.3%) was similar in the two groups.
Conclusions. The INV and CON strategies resulted in similar favorable outcomes at 1 year of
follow-up. In particular, the rates of mortality and reinfarction were not different and were
impressively low in both groups. One possible advantage of the INV strategy was detected in
subgroup analyses. In patients with a history of myocardial infarction, the data are suggestive
that l-year mortality was lower in INV patients (10.3%) than in CON patients (17.0%)
(p=0.03). (Circulation 1992;85:533-542)
T he Thrombolysis in Myocardial Infarction
(TIMI) Phase II Trial is a randomized multicenter clinical investigation that was designed to compare two management strategies for
patients with acute myocardial infarction (AMI)
treated with thrombolytic therapy. The invasive strategy (INV) involved the routine performance of cardiac catheterization and coronary revascularization
by means of percutaneous transluminal coronary
angioplasty (PTCA) or coronary artery bypass graftFrom the Division of Cardiology, Department of Medicine,
Rhode Island Hospital, Program in Medicine, Brown University,
Providence, R.I., and TIMI Sites (see "Appendix").
Address for correspondence: David 0. Williams, MD, Division
of Cardiology, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903.
Supported by research contracts and grants from the National
Heart, Lung, and Blood Institute, Bethesda, Md.
Received October 8, 1990; revision accepted October 8, 1991.
ing (CABG). The conservative strategy (CON) used
catheterization and revascularization only when
prompted by episodes of spontaneous or provoked
ischemia. At 6 weeks of follow-up, there was no
apparent benefit of one strategy over the other when
judged according to the occurrence of certain important clinical end points including death, nonfatal
reinfarction, and the extent of left ventricular dysfunction.1 Because the potential benefits of one
strategy, however, might not be detected within 6
weeks after AMI, TIMI II patients have been followed in an effort to determine whether differences
in outcome, based on initial strategy assignment,
might become evident. Accordingly, the purpose of
this report is to provide information on all patients
randomized and to describe the results of the TIMI
II Trial at 1 year of follow-up. The specific aims are
to determine the incidence of certain clinical events
534
Circulation Vol 85, No 2 February 1992
and the chronology of these events in the randomized cohort and to analyze outcome for selected
clinical subgroups.
See p 839
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Methods
Details of the TIMI II Trial have been described
previously.1 In brief, consenting patients <76 years of
age with greater than 30 minutes of chest pain
characteristic of myocardial ischemia, diagnostic
electrocardiographic ST segment elevation, presentation within 4 hours of pain onset, and no contraindications to thrombolytic therapy received a 6-hour
infusion of recombinant tissue-type plasminogen activator (rt-PA) alteplase, (Activase®) and were randomly assigned to either the INV or CON strategies.
Patients also received heparin and aspirin. Those
assigned to the INV strategy underwent routine
cardiac catheterization including left ventricular and
coronary cineangiography within 18-48 hours of
randomization and PTCA if catheterization findings
demonstrated appropriate anatomy. Aspirin was part
of recommended study treatment for all invasive
strategy patients before PTCA. CABG was recommended for INV patients if coronary anatomy was
too complex or hazardous for PTCA. Patients assigned to the CON strategy underwent these procedures only in response to either spontaneous or
provoked myocardial ischemia. Patients eligible for
enrollment in the trial of ,3-blocker therapy (TIMI II
B), were randomized to either the immediate or
delayed administration of metoprolol. One-year results were presented previously2 and will not be
discussed.
Research nurse coordinators from each participating clinical site were trained, tested, and certified in
the performance of collection, recording, and transfer of data to the coordinating center. For each
patient, outcome was determined at the time of
hospital discharge, 6 weeks after enrollment, and at 1
year from the time of recruitment. Patient status was
determined by a formal clinic visit at 6 weeks and 1
year and by telephone contact at 3 and 6 months.
Compilation, editing, and analysis of data were performed by the coordinating center.
End Points
In TIMI II, the primary end point for comparing
the invasive and conservative strategies was survival
free of recurrent myocardial infarction at 42 days.1
The present analysis extends the TIMI II results in a
secondary analysis to 1 year of follow-up.
In this analysis, survival data are based on all-cause
mortality, including fatal myocardial infarction. Patients were also monitored for clinical events including myocardial ischemia. Recurrent chest pain in the
hospital refers to chest pain that occurred with or
without myocardial infarction at least 18 hours after
study entry but during the hospital stay. Severe
ischemic event in patients after discharge refers to
chest pain occurring with or without myocardial
infarction for which the patient was admitted to the
hospital. Myocardial infarction was diagnosed when
the patient had prolonged chest pain with characteristic electrocardiographic changes and/or confirmatory cardiac enzymes. Events reported by the research nurse coordinators were classified by the
Mortality and Morbidity Classification Committee.
Members of this committee were cardiologists who
were not TIMI clinical center investigators; events
were classified without knowledge of treatment assignment and according to criteria established before
the classification of these events began. The Mortality and Morbidity Classification Committee reviewed
and classified all reported myocardial infarction
events. The classification criteria were different for
events within 18 hours from study entry to allow only
new events to be classified as reinfarction. In this
analysis, reinfarction data are based on all new
myocardial infarction after the qualifying infarction
and including new, fatal myocardial infarctions.
Strokes include all events since randomization, both
during the initial hospitalization and after the initial
hospitalization. Only neurological events occurring
during the initial hospitalization were reviewed by two
neurologists who were not TIMI clinical center investigators and have been described in detail.3
Statistical Methods
For discrete data variables, comparisons of proportions of patients having the given attribute were
made with a x2 test.4 For continuous data variables,
comparisons of mean values were made with a twotailed Student's t test.5 Cumulative event rates were
estimated using the product-limit (Kaplan-Meier)
method,6 and comparisons in the event distributions
over time were made using the log-rank statistic.
These analyses were performed using Statistical
Analysis System (SAS) programs.7 All analyses are
based on a data file (including all follow-up information) established January 1991. To adjust for multiple
testing, a value of p<0.01 was specified as indicating
statistical significance for the treatment comparisons
with respect to the primary end point (combined
mortality and reinfarction 6 weeks after thrombolytic
therapy). For comparisons of other end points, probability values between 0.01 and 0.001 provide some
evidence of differences between treatments, and
probability values <0.001 provide strong evidence of
such differences. All tests of differences were
planned as two-tailed tests in the TIMI II design.
The effects of treatment strategy, selected baseline
characteristic, and the interaction of treatment strategy and baseline characteristic were evaluated using
a Cox proportional hazards regression model. A test
of the hypothesis that the interaction effect is zero
was performed to determine whether the difference
in events between the two treatment strategies was
the same for patients with and without the characteristic. Cox regression models were also used to
estimate relative risks and confidence intervals for
Williams et al One-Year Results of TIMI Phase II Trial
535
Comparison of Randomized Cohorts
The primary response variable for the TIMI LI Trial
was the combined end point of death and nonfatal
reinfarction. From time of enrollment to 52 weeks,
there was no difference between INV and CON
patients in the incidence of death and reinfarction
(Table 2). The relative risk of the combined end point
for invasive strategy patients compared with conservative strategy was 0.98 (99% confidence interval, 0.781.24). When analyzed as individual end points, the
incidence of death and of AMI were impressively low
for both groups at 1 year and were not significantly
different. The 1-year cumulative mortality in the INV
group was 6.9% and for the CON patients it was 7.4%
(relative risk, 0.93; 99% confidence interval, 0.671.30). The cumulative incidence of recurrent AMI at 1
year was 9.4% and 9.8%, respectively (relative risk,
0.97; 99% confidence interval, 0.73-1.30).
Similar patterns were noted for death and reinfarction in the two groups (Figures 1-3). Most events
occurred within 6 weeks after the infarction that
qualified the patient for TIMI. For the INV patients,
most events occurred during hospitalization. Early
during hospitalization, reinfarction was more common
in INV patients (p=0.005 through 1 week).
At the 1-year follow-up visit, there was no difference in the proportion of patients experiencing angina or in the severity of angina based on the
Canadian Cardiovascular Society Angina Classification System. During the first year of follow-up, however, more patients in the CON group were rehospitalized for angina than in the INV group (19.6%
1-year end points. These analyses were performed
using BioMedical Data Package (BMDP) programs.8
Results
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The preliminary report on the first 6 weeks of
follow-up' was based on data for patients recruited
before June 5, 1988, or 3,162 of the 3,339 enrolled at
the end of recruitment. As before, there were no
important differences between the 1,681 assigned to the
INV strategy and the 1,658 assigned to the CON
strategy (Table 1). Patients in both strategies were for
the most part men who were experiencing their first
myocardial infarction, <70 years of age, and approximately two thirds had at least one clinical characteristic
indicative of increased risk for infarct-related mortality.
Approximately half had anterior wall infarction.
The vital status of all patients 6 weeks after entry
was known; however, three patients in the invasive
strategy and three patients in the conservative strategy could not be contacted after hospital discharge to
obtain information on nonfatal events. Thus, the
follow-up for nonfatal events at 6 weeks was available
for 99.8% of patients in both strategies.
At 1 year, the vital status of 11 patients in the
invasive group and 12 in the conservative group could
not be ascertained. Accordingly, follow-up for mortality was complete for 99.3% of patients in both strategies. A small number of patients for whom vital status
was known did not have complete information on
nonfatal events available (19 in the invasive group and
16 patients in the conservative group). Thus, follow-up
for nonfatal events at 1 year was 98.2% and 98.3% in
the invasive and conservative strategies, respectively.
TABLE 1. Baseline Characteristics in TIMI Phase II
Conservative
Invasive
n
Age (mean years)
Race (white)
Sex (male)
Not low risk
Age >70 years
Prior MI
Anterior MI
Rales .1/3 lung fields
Hypotension and sinus tachycardia
Atrial fibrillation or flutter
Pulmonary edema
Cardiogenic shock
Other risk factors
History of angina
History of CHF
History of hypertension
History of diabetes mellitus
Ongoing chest pain at rt-PA initiation
Time from onset of pain to study entry (mean hours)
MI, myocardial infarction; CHF, congestive heart failure.
1,681
1,477
1,382
1,106
208
233
850
63
93
34
18
26
918
53
655
217
1,489
1,681
(n =1,681)
%
56.8
87.9
82.2
65.8
12.4
13.9
50.6
3.8
5.5
2.0
1.1
1.6
54.7
3.2
39.0
12.9
88.6
2.6
(n= 1,658)
n
1,658
1,471
1,360
1,120
181
235
880
71
94
39
16
24
880
39
624
222
1,463
1,658
%
56.8
88.7
82.0
67.6
10.9
14.2
53.1
4.3
5.7
2.4
1.0
1.4
p
0.95
0.44
0.89
0.28
0.19
0.80
0.15
0.43
0.86
0.52
0.76
0.81
53.1
2.4
37.6
13.4
88.2
2.7
0.35
0.16
0.43
0.68
0.76
0.44
536
Circulation Vol 85, No 2 February 1992
TABLE 2. Clinical Events Through 1-Year Follow-up in TIMI Phase II
Invasive
(n = 1,681)
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Cumulative event rates (Kaplan-Meier estimates)
Death (all causes)
21 Days
6 Weeks
1 Year
Reinfarction (fatal and nonfatal)
21 Days
6 Weeks
1 Year
Death and reinfarction
21 Days
6 Weeks
1 Year
Recurrent ischemia
Recurrent chest pain in hospital during first 10 days
Severe ischemic event
21 Days
6 Weeks
1 Year
Death, reinfarction, or recurrent ischemia
Death, reinfarction, or recurrent chest pain in hospital
during first 10 days
Death, reinfarction, or severe ischemic event
21 Days
6 Weeks
1 Year
Stroke
21 Days
6 Weeks
1 Year
Cumulative procedure rates (Kaplan-Meier estimates)
Cardiac catheterization*
21 Days
6 Weeks
1 Year
PTCA
21 Days
6 Weeks
1 Year
CABG
21 Days
6 Weeks
1 Year
PTCA or CABG
21 Days
6 Weeks
1 Year
versus 14.7%, respectively; p<0.001). Similarly, rehospitalization for cardiac reasons was observed
more commonly in CON patients (38.1%) than in
INV patients (29.6%,p<0.001). There was no differ-
Conservative
(n = 1,658)
n
S
83
88
116
4.9
5.2
6.9
68
77
123
4.1
4.6
7.4
0.25
0.43
0.59
109
114
153
6.7
7.0
9.4
98
108
157
6.1
6.7
9.8
0.43
0.67
0.81
177
187
247
10.5
11.1
14.7
153
168
251
9.2
10.1
15.2
0.18
0.31
0.83
415
25.5
467
29.8
0.05
215
241
394
13.0
14.7
24.3
219
272
442
13.5
16.8
27.6
0.81
0.14
0.04
460
27.8
510
32.0
0.06
275
306
477
16.4
18.2
28.5
269
327
527
16.2
19.7
31.9
0.83
0.36
0.05
23
25
32
1.4
1.5
2.0
20
21
25
1.2
1.3
2.0
0.67
0.57
0.37
1,598
1,601
1,610
97.1
97.4
98.0
444
523
722
27.5
32.5
45.2
989
993
1,003
60.2
60.5
61.2
202
229
326
12.5
14.2
20.5
188
206
281
11.6
12.7
17.5
146
184
275
9.1
11.5
17.3
1,130
1,145
1,182
69.0
69.9
72.3
333
396
566
20.7
24.6
35.5
n
S
p
ence in the total days of rehospitalization between
the two groups. The incidence of stroke during
follow-up in the two groups was the same (2.0%) at 1
year.
Williams et al One-Year Results of TIMI Phase II Trial
537
TABLE 2. Continued.
Invasive
Conservative
(n=1,681)
(n= 1,658)
%
n
n
%
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Canadian heart angina class
Six weeks
Patients with follow-up visit
1,436
85.4
1,420
Canadian Cardiovascular Society Angina classt
Class 0
1,123
78.2
1,093
Class I
198
13.8
201
Class II
80
5.6
86
Class III
25
1.7
27
Class IV
10
0.7
13
One year
Patients with follow-up visit
76.4
1,285
1,260
Canadian Cardiovascular Society Angina classt
Class 0
969
75.5
972
Class I
196
15.3
200
Class II
86
6.7
64
Class III
23
1.0
13
Class IV
10
0.8
10
Missing
1
1
PTCA, percutaneous transluminal coronary angioplasty; CABG, coronary artery bypass grafting.
*Patients requiring catheterization in the conservative strategy.
tDenominators for these percentages are the numbers of patients with follow-up visits.
p
85.6
77.0
14.2
6.1
1.9
0.9
0.91
76.0
0.21
77.2
15.9
5.1
1.0
0.8
As expected from the trial design, early (within 21
days) cardiac catheterization was performed in
nearly all (97.2%) INV patients and less commonly
(27.5%, p<0.001) in CON patients. Only 0.9% of
additional INV patients underwent cardiac catheterization during 1 year of follow-up in contrast to the
CON cohort in whom the cumulative incidence of
cardiac catheterization by 1 year had increased to
45.2%. Second catheterizations were performed in
24.9% of INV patients and in 25.8% of CON patients
within 1 year after study entry (p=0.65). In the
conservative strategy, those patients who developed
myocardial ischemia spontaneously or during exer-
cise testing or had reinfarction or hemodynamic
deterioration were to undergo catheterization and
revascularization if the anatomy was suitable.
Study protocol called for PTCA to be performed if
the coronary anatomy was suitable early during hospitalization for patients assigned to INV strategy.
Through the first 3 weeks after entry (Table 2),
PTCA was performed in 60.2% of INV patients
compared with 12.5% of CON patients (p<0.001).
By 6 and 52 weeks, respectively, 14.2% and 20.5% of
CON patients had undergone PTCA, whereas only
1% of additional INV patients underwent the procedure. Thus, PTCA was performed much more fre-
CUMULATIVE RATES OF DEATH OR REINFARCTION THROUGH ONE YEAR
TIMI 11
CUMULATIVE RATES OF DEATH THROUGH ONE YEAR
TIMI 11
20
15
INVASIVE
CONSERVATIVE
z
010
5L
5
-
7-----
cz
-. INVASIVE
-
CONSERVATIVE
u.
0
FIGURE 1. Graph of cumulative Kaplan-Meier event rates
for death or reinfarction according to strategy assessment from
entry through 52 weeks.
8
16
24
32
40
48
56
WEEKS AFTER STUDY ENTRY
WEEKS AFTER STUDY ENTRY
FIGURE 2. Graph of cumulative Kaplan-Meier event rates
for death according to strategy assignment from entry through
52 weeks.
538
Circulation Vol 85, No 2 February 1992
CUMULATIVE RATES OF REINFARCTION THROUGH ONE YEAR
TIMI 11
20j
INVASIVE
CONSERVATIVE
z
15
-------
---------------------
1
1
:1
at 1 year (interaction,p=0.03). Patients with a history
of AMI assigned to the INV strategy had a lower
42-day mortality (6.0%) compared with those assigned to the CON strategy (11.5%, p=0.04). Oneyear mortality in patients with prior AMI was 10.3%
and 17.0% in the INV and CON groups, respectively
(p=0.03). These suggestive differences were not
changed by analyses to adjust for other baseline
characteristics. Revascularization by either PTCA or
CABG was performed in 74.8% of patients with prior
AMI assigned to the INV strategy compared with
41.0% of those in the CON group.
09FF
1
40
48
56
16
24
8
32
Discussion
WEEKS AFTER STUDY ENTRY
Considerable effort was devoted to the planning of
TIMI II so that it would be directly applicable to
clinical practice in managing patients with AMI.
TIMI II was a trial designed to compare two treatment strategies rather than a specific therapy or
intervention. The assigned strategies were implemented early in the patient's course, similar to the
clinical setting wherein a plan for subsequent hospital care for an AMI patient begins immediately
following presentation.
The invasive strategy was developed on the presumption that thrombolytic therapy may be effective
in establishing reperfusion but could leave uncorrected a severe residual atherosclerotic narrowing of
the coronary artery responsible for the infarction.
This "partially treated" condition could render the
patient susceptible to reinfarction because of early
reclosure of the coronary artery or recurrent ischemia related to persistent significant partial obstruction.9410 PTCA after thrombolytic therapy offered the
potential benefit of relieving residual atherosclerotic
narrowing'1 and thus reducing the likelihood of
recurrent ischemia-related events.
To provide PTCA the greatest opportunity to
demonstrate efficacy and safety after thrombolytic
therapy, this procedure was performed only when
coronary anatomy was suitable for PTCA as judged
by the results of cardiac catheterization and angiography. Accordingly, patients with patent yet significantly stenosed infarct arteries with coronary anatomic characteristics that did not preclude PTCA
were selected for the procedure. Such patients could
be considered as those who might receive the greatest benefit from the procedure because they had
achieved reperfusion but had severe residual coronary narrowing. Patients with coronary anatomy
known to be associated with an increased risk of
PTCA related untoward events, for example, left
main disease or its equivalent, were excluded and
referred for CABG.1213 In addition, patients with
totally occluded arteries at 18-48 hours did not
undergo PTCA unless recurrent ischemia had occurred. Not performing a PTCA in such patients
reduced the chance of a PTCA-related adverse event
in patients in whom the likelihood of benefit from
PTCA is low. Thus, by design, PTCA was not performed in each patient assigned to the INV strategy
0
FIGURE 3. Graph of cumulative Kaplan-Meier event rates
for reinfarction according to strategy assignment from entry
through 52 weeks.
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quently in the INV patients, almost five times as
much during the period of initial hospitalization.
Periprocedural (within 24 hours) mortality for PTCA
in the INV group was 0.6%, with a reinfarction rate
of 4.5%. The number of CON patients undergoing
PTCA from 6 weeks to 1 year was small (6.3%). More
patients in the INV group had CABG by 3 weeks
(11.6%) than in the CON group (9.1%, p=0.01). At
6 weeks and at 1 year, the cumulative number of
patients who received CABG was similar in the two
groups (CON, 11.5% and 17.3%; INV, 12.7% and
17.5%, respectively).
Of the 972 INV patients who had PTCA during the
first 6 weeks from enrollment and survived to 6
weeks, 104 (10.8%) had an additional revascularization procedure within the 1-year follow-up. A second
PTCA was performed in 66 (6.8%), whereas 46
(4.8%) had CABG, of which eight had both procedures. Of 224 CON patients who had PTCA within 6
weeks, a second PTCA was performed in 18 (8.1%),
whereas CABG was carried out in 12 (5.4%) during
follow-up. There was no difference in the proportion
of INV versus CON patients who required a second
revascularization procedure.
Nonrandomized Subset Analysis
The cumulative 1-year event rates for death and
reinfarction were analyzed in various subsets of
INV and CON patients. There was no difference in
the occurrence of death or reinfarction between
INV and CON strategy patients when analyzed in
terms of sex, age greater or less than 70 years,
anterior or nonanterior infarction location, time to
t-PA therapy greater or less than 2 hours, low-risk
or not-low-risk class, presence or absence of shock,
catheterization performed or not performed during
hospitalization, or CABG performed or not performed during hospitalization.
A difference in outcome was noted between patients with and without prior myocardial infarction at
42 days (interaction, p =0.004) but was not as strong
Williams et al One-Year Results of TIMI Phase II Trial
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but rather in those in whom the greatest potential
benefit was anticipated.
The 1-year mortality of the INV and CON groups
was not significantly different. Thus, the INV strategy
did not enhance survival in an important way in
comparison with the CON strategy. However, the
mortality rates of the INV and CON groups were
both low. Hence, the similarity between INV and
CON patients was not attributable to INV patients
fairing worse than expected; rather, the CON patients did well. In fact, the 1-year mortality rate
(7.4%) of CON patients was lower than that previously reported in other studies of patients treated
with intravenous t-PA (10.5%),14 streptokinase
(10.5-17.2%),14-16 or anisoylated plasminogen streptokinase activator complex (10.8%).17 Although substantial differences between TIMI II and these other
trials exist, none of the other trials incorporated the
standardized use of cardiac catheterization, PTCA,
or surgery, an integral component of the CON strategy in TIMI II. The favorable results of the TIMI II
CON group could not be attributed to the selection
of less-ill patients because 67% of patients had
features of increased risk and patients with pulmonary edema or cardiogenic shock were not excluded.'
The rates of reinfarction and death or reinfarction at
1 year were also similar in both groups. With 1,650
patients in each group, there would be 80% power to
detect a clinically important reduction of 27% or
more in event rates when the higher rate was 15%
(a=0.01 by two-sided test).
Early during hospitalization, reinfarction was more
common in the INV group. Although not statistically
different, the rate of reinfarction in the CON group
was slightly higher at 1 year (9.8% versus 9.4%) in
comparison with the INV group. Because reinfarction was more frequent in the INV group during the
early period but the cumulative rate was lower at 1
year, one might speculate that the rate at which
reinfarction occurred over the course of 1 year might
in fact be lower in the INV group compared with the
CON group. The observed incidence of reinfarction
from 6 weeks to 1 year in the INV group was 2.9%
and in the CON group 3.3% (p=NS). Of additional
note is that because the reinfarction rate in the INV
group occurred early during the hospitalization, it
may have been associated with procedural aspects of
acute cardiac catheterization and PTCA. Should
further technological advances reduce the incidence
of complications associated with these procedures,
true benefit in reducing the incidence of reinfarction
in the INV arm might become evident.
For patients assigned to the CON strategy, the
incidence of death or recurrent AMI beyond 6 weeks
was low. This observation is of particular interest in
respect to the CON group because the majority of
patients (72.5%) did not undergo either in-hospital
cardiac catheterization or revascularization. Had the
CON strategy been inadequate in identifying appropriate patients for revascularization, one might have
expected an increased incidence of events beyond 6
539
weeks. The low rate of late events suggests that using
the occurrence of spontaneous or provokable ischemia as an indication for more aggressive evaluation
is a reasonable screening mechanism to identify
patients at increased risk for recurrent infarction.
Follow-up beyond 1 year will be helpful in confirming
these results.
In the INV group, PTCA was performed in about
60% of patients during the hospitalization and in a
few additional patients thereafter. It was expected
that all patients would not undergo in-hospital
PTCA. This procedure is acknowledged as not being
applicable to all patients with coronary disease, and
there are situations in which PTCA is clearly known
to be hazardous. In fact, application of PTCA routinely to patients with AMI has been associated with
a mortality in excess of that after thrombolytic therapy alone.18
In comparison with the INV group, PTCA was
performed in only 12.5% of CON patients within 2
weeks and 14.2% by 6 weeks, substantially less than
that of the INV group. Additional PTCA beyond 6
weeks was performed in only 6.3% of CON patients.
By design, some use of PTCA was anticipated in the
CON group because the protocol called for this
procedure to be performed in response to evidence
of ischemia. Nevertheless, there was nearly a threefold difference at 1 year in the use of PTCA in INV
compared with CON groups. From these observations, for the types of patients studied in TIMI II and
for the dose regimen of t-PA used, one out of seven
patients will need PTCA before hospital discharge.
Although there are many more patients in whom
PTCA could be done, performing the procedure in
such patients appears to offer no additional benefit.
PTCA after 21 days was performed more often in
patients in the CON group than in the INV group.
This small but significant difference in additional
procedures may have been in response to episodes of
late ischemia because more CON patients (19.6%)
than INV patients (14.7%) were rehospitalized for
angina during the 1-year follow-up. This explanation
may also apply for the 8.2% of additional patients in
the CON group who underwent CABG from 21 days
to 1 year.
Regardless of initial strategy assignment, most
(76%) TIMI II patients did not report angina pectoris at the 1-year visit. Only 2.6% of the INV and 1.8%
of the CON groups had severe (Canadian class III or
IV) angina. These results are similar to prior observational data in which PTCA was performed in
coronary disease patients with angina as an indication. The recent NHLBI Registry described an incidence of freedom from angina at 1 year of 76%.19
TIMI II was designed to test the hypothesis that an
aggressive strategy was superior to a more conservative one in patients treated with intravenous rt-PA in
the early hours of AMI. Superiority of the INV
strategy was not detected for the large cohort of
patients studied. Because it is conceivable, however,
that a certain subset of AMI patients could benefit
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from a more aggressive approach, additional "hypothesis-generating" analyses of selected subgroups
were performed. For nearly all characteristics evaluated, no differences in outcome were observed between INV and CON groups.
However, a lower 6-week mortality that was not as
marked at 1 year was observed in INV versus CON
for patients with a history of myocardial infarction.
This finding cannot be ascribed to features of the
trial design and may reflect a true treatment effect of
the INV strategy. A definitive explanation of why
such patients would benefit from an INV approach
cannot be derived from the data base of this trial. On
protocol angiography, INV patients with prior myocardial infarction did have a greater prevalence of
multivessel disease than INV patients without prior
myocardial infarction (60.2% versus 28.3%, respectively, p<0.001). Also for INV patients, the left
ventricular function was more compromised in those
with prior myocardial infarction than without (mean
ejection fractions of 42.1% and 48.3%, respectively;
p<0.001). Routine PTCA in such a group could be
beneficial because surgical revascularization has
been shown to enhance survival in patients with
advanced coronary artery disease, particularly in
those with impaired left ventricular function.20-22
Although no trial has yet demonstrated that PTCA
can enhance survival in comparison with medical
therapy, PTCA is acknowledged as a very potent and
effective alternative means of relieving coronary narrowing and normalizing coronary circulatory dynamics. Offering routine revascularization to patients
with more advanced disease may prove to be valuable
after rt-PA for AMI. It is important to note, however,
the limitations of retrospective subset analysis. At
best, these data suggest that a benefit of routine
PTCA in patients with prior AMI may exist. Additional investigation is required to confirm whether
this hypothesis is correct.
Conclusions
INV and CON strategies after intravenous t-PA in
AMI result in similar favorable 1-year outcomes. The
favorable outcome of the CON group was achieved
without excessive late PTCA or CABG and is indicative of a rather stable patient population. The initial
conclusion of TIMI II, namely that an INV strategy
assessed in terms of mortality and reinfarction is not
superior to a CON strategy, remains valid.
Appendix
TIMI
Phase II Trial
Participants in the
Study chairman: E. Braunwald, MD, Harvard University, Boston. Coordinating center: Maryland Medical Research Institute, Baltimore (principal investigator: G.L. Knatterud, PhD; coinvestigators: M.L.
Terrin, MD, MPH; S. Forman, MA; D.T. Harris; R.
Ross, MSc; P.C. Wilkins, BS; M. Frederick, PhD;
P.L. Canner, PhD; M. Carroll; J. Depkin, BS; J.
Dotson; C. Fiery; M. Johnson; C. Kelly; P. Noble, BS;
B. Thompson, PhD; W.R. Bell, MD; and L. Scherlis,
MD). Radiographic core laboratory: University of
Washington, Seattle (principal investigator: H.T.
Dodge, MD; coinvestigators: B.G. Brown, MD, PhD;
J.W. Kennedy, MD; F.H. Sheehan, MD; B. Bisson;
and E. Bolson, MS). Radionuclide core laboratory:
Yale University, New Haven, Conn. (principal investigator: B. Zaret, MD; coinvestigator: F. Wackers,
MD; D.S. Kayden, MD; K. Davis, RTNM; and R.
Green, RTNM). Coagulation core laboratory: University of Vermont, Burlington (principal investigator: K. Mann, PhD; coinvestigators: D. Stump, MD;
D. Collen, MD; E. Bovill, MD; and R. Tracy, PhD).
Electrocardiographic core laboratory for qualifying
electrocardiograms: George Washington University,
Washington, DC (principal investigator: A.M. Ross,
MD; coinvestigators: G.B. Bren, MD; and A.G.
Wasserman, MD). Electrocardiographic core laboratory for exercise electrocardiograms: St. Louis University, St. Louis, Mo. (principal investigator: B.R.
Chaitman, MD; coinvestigators: R.D. Wiens, MD; L.
Shaw, MS; M. Haueisen, BS; and L.T. Younis, MD,
PhD). National Heart, Lung, and Blood Institute
Program Office: National Institutes of Health, Bethesda, Md. (principal investigator: E.R. Passamani,
MD; coinvestigators: T.L. Robertson, MD; G. Lan,
PhD; R. Solomon, MHS; and G. Sopko, MD). Pathology core laboratory: National Institutes of
Health, the Clinical Center, Bethesda, Md. (principal
investigator: W.C. Roberts, MD; coinvestigator: J.
Kalan, MD). Percutaneous transluminal coronary
angioplasty quality control laboratory: Brown University, Providence, R.I. (principal investigator: D.O.
Williams, MD; coinvestigators: R. Riley, MD; H.
White, MD; B. Sharaf, MD; F. Fedele, MD; E.
Thomas, MD; T. Drew, MD; J. Joelson, MD; and D.
Hardink, RN). Drug distribution center: Cooperative
Studies Program, Veterans Administration Medical
Research Service, Albuquerque, N.M. (principal investigator: C. Colling, RPh, MD; coinvestigators: C.
Haakenson, RPh, MS; and M. Sather, RPh, MS).
Clinical Centers
Albert Einstein College of Medicine-Monteflore
Medical Center, New York (principal investigator:
H.S. Mueller, MD; coinvestigators: M.A. Greenberg,
MD; R. Grose, MD; G. Gordon, MD; J.D. Goldfischer, MD; M. Bensman, MD; J. Cooper, MD; B.
Ventura, RN; K. Hemingway, RN; M. Stein, RN; P.
Michaud-Edelstein, RN; L. Henson, RN; J. Durkin,
RN; and P. Murphy, RN); Baylor College of Medicine, Houston, Tex. (principal investigator: R. Roberts, MD; coinvestigators: P. Nelson, RN; S. Minor,
MD; C. Pratt, MD; A. Raizner, MD; W.L. Winters,
MD; M.S. Verani, MD; J.M. Lewis, MD; J. Heibig,
MD; N. Kleiman, MD; and M.K. VanderMolen,
RN); Baystate Medical Center, Springfield, Mass.
(principal investigator: M.J. Schweiger, MD; coinvestigators: R.E. Gianelly, MD; T. Marantz, MD; M.
Porway, MD; E. Brickman, RN; F. Blank, RN; and J.
Mitchell, RN); Boston University Medical Center,
Williams et al One-Year Results of TIMI Phase II Trial
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Boston (principal investigator: T.J. Ryan, MD; coinvestigators: C.S. Apstein, MD; J.B. Cadigan III, MD;
D.P. Faxon, MD; A.K. Jacobs, MD; M.A. Kellett Jr.,
MD; B.J. Polansky, MD; N.A. Ruocco, MD; T.A.
Sanborn, MD; T. Varricchione, RRT; D.A. Weiner,
MD; N. Battinelli, RN; and B. Hankin, RN); Bridgeport Hospital, Bridgeport, Conn. (principal investigator: J.D. Babb, MD; coinvestigators: Z.A. Adefuin,
MD; M. Driesman, MD; J. Meizlish, MD; and D.
Yasick, RN); Brown University, Providence, R.I.
(principal investigator: D.O. Williams, MD; coinvestigators: T.M. Drew, MD; R.S. Riley, MD; H.J.
White, MD; D. Shefcyk, MD; J. Joelson, MD; E.
Thomas, MD; B. Sharaf, MD; F. Fedele, MD; M.
Nathanson, MD; G. McKendall, MD; D. Becker,
MD; D.L. Hardink, RN; M. Macedo, RN; G. Weeks,
MD; R. Mich, MD; and E. Berger, MD); Columbia
University, New York (principal investigator: E.
Powers, MD; coinvestigators: A. Berke, MD; L.
Johnson, MD; A.B. Nichols, MD; D.S. Reison, MD;
A. Schwartz, MD; R. Watson, MD; E. Escala, RN;
H.S. Wasserman, MD; and M. Apfelbaum, MD);
Cornell Medical Center, New York (principal investigators: J.S. Borer, MD; and T.L. Schreiber, MD;
coinvestigators: D.H. Miller, MD; J.W. Moses, MD;
I. Tamari, MD; B. Charash, MD; B. Gerling, MD;
D.A. Silvasi, RN; and A. McNulty, RN); George
Washington University, Washington, DC (principal
investigator: A.M. Ross, MD; coinvestigators: G.B.
Bren, MD; R.I. Katz, MD; R.H. Leiboff, MD; P.J.
Varghese, MD; A.G. Wasserman, MD; M. Magee,
RN; G. Carvallo, RN; J. Mendelson, RN); Harvard
University, Boston (principal investigator: D.S. Baim,
MD; coinvestigators: D. Diver, MD; S. Herson, MD;
J.E. Markis, MD; R.G. McKay, MD; B. Lorell, MD;
C. (Brewer) Senerchia, RN, MS; G.A. Carey, RN;
and J. Schweiger, RN); Maine Medical Center, Portland (principal investigator: C.T. Lambrew, MD;
coinvestigators: W.D. Alpern, MD; R.A. Anderson,
MD; D.J. Cutler, MD; J.P. Driscoll, MD; M. Kellett,
MD; J.C. Love, MD; P.R. Minton, MD; R.L. Morse,
MD; P.K. Shaw, MD; P.W. Sweeney, MD; S. Vermilya, RN; P. Birmingham, RN; and N. Mclntire, RN);
Mayo Foundation, Rochester, Minn. (principal investigator: J.H. Chesebro, MD; coinvestigators: D.R.
Bresnahan, MD; B.J. Gersh, MD; F.A. Miller, MD;
M.B. Mock, MD; H.C. Smith, MD; R. Frye, MD;
D.L. Hayes, MD; I. Clements, MD; W.K. Freeman,
MD; J.A. Rumberger, MD; R. Gibbons, MD; R.
Nishimura, MD; R. Rodeheffer, MD; R. Click, MD;
J. Oh, MD; L. Sinak, MD; D. Klees, LPN; L. Meyers,
LPN; R. Vliestra, MD; J. Bresnahan, MD; D.
Holmes Jr., MD; and G. Reeder, MD); New York
Medical College, Valhalla, N.Y. (principal investigator: M.V. Herman, MD; coinvestigators: M.B. Weiss,
MD; M. Cohen, MD; J. Levy, MD; M. Feld, MD; R.
Grief, MD; J.H. Stein, MD; R. Wallach, MD; A.M.
Kanakaraj, RN; V. Rosal-Greif, RN; and Y. Sait,
PA); New York University, New York (principal
investigator: F. Feit, MD; coinvestigators: J.N. Slater,
MD; A. Simon, RN; J. Breed, RN; M.S. Nachamie,
541
MD; W.J. Cole, MD; I.C. Schulman, MD; M.J. Rey,
MD; M. Attubato, MD; and S. Shapiro, RN); North
Shore University, Manhasset, N.Y. (principal investigator: J. Morrison, MD; coinvestigators: V. Padmanabhan, MD; P. Reiser, MD; L. Ong, MD; S.
Green, MD; A. Tortolani, MD; M.L. Andresen, RN;
T. Imhof, RN; L. Genovese, RN; and M. Ward, RN);
Northwestern University, Evanston, Ill. (principal
investigator: R. Davison, MD; coinvestigators: T.
McDonough, MD; B. Kramer, MD; S. Meyers, MD;
P. Niemyski, RN; M. Parker, RN; K. Kaplan, MD; D.
Fintel, MD; M. Salinger, MD; D.C. Hueter, MD; G.
Wilner, MD; C. Berkowitz, MD; and K. Duun, RN);
St. Louis University, St. Louis, Mo. (principal investigator: B.R. Chaitman, MD; coinvestigators: M.G.
Vandormael, MD; M.J. Kern, MD; W.P. Hamilton,
MD; J.G. Dwyer, MD; T. Thornton, RN; J. Anthony,
RN; K. Galan, RN; M. Major, RN; and G. Huber,
RN); University of Alabama, Birmingham (principal
investigator: W.J. Rogers, MD; coinvestigators: J.G.
Arciniegas, MD; W.A. Baxley, MD; R.C. Bourge,
MD; T.M. Bulle, MD; T.B. Cooper, MD; L.S. Dean,
MD; R. Hess, DO; W.A.H. MacLean, MD; S.E.
Papapietro, MD; C. Saenz, MD; A.W.H. Stanley,
MD; M.T. Simpson, MD; K. Bynum, RN; T. Eubanks, RN; and L. Maske, RN); University of Massachusetts, Worcester (principal investigator: J.
Gore, MD; coinvestigators: J.S. Alpert, MD; J.R.
Benotti, MD; J. Leppo, MD; I.S. Ockene, MD; J.F.
Rippe, MD; B.H. Weiner, MD; J. Dalen, MD; J.M.J.
Gaca, MD; S.P. Ball, RN; J. Corrao, RN; and C.
Mahan, RN); University of Minnesota, Minneapolis
(principal investigator: M. Hodges, MD; coinvestigators: W.T. Hession, MD; S.W. Sharkey, MD; D.
Wysham, MD; I. Goldenberg, MD; A. Adicoff, MD;
R. Brandenburg Jr., MD; F.L. Gobel, MD; L. Nordstrom, MD; R. Van Tassel, MD; C. White, MD; R.
Wilson, MD; A. Ettinger, RN; L. Palmquist, RN; C.
Siebold, RN; N. Carruthers, RN; and C. Farmer,
RN); University of Texas, Dallas (principal investigator: J. Willerson, MD; coinvestigators: L.D. Hillis,
MD; G.J. Dehmer, MD; D.L. Brown, MD; M. Winniford, MD; B.G. Firth, MD; M.M. Carry, MD; B.
Toates, RN; S. Cochran, RN; P. Surratt, RN; and J.
Moore, RN, MSN); Washington University, St.
Louis, Mo. (principal investigator: P.A. Ludbrook,
MD; coinvestigators: A.J. Tifenbrunn, MD; N.A.
Ricciotti, RN, MSN; A.S. Jaffe, MD; and B.E. Sobel,
MD); William Beaumont Hospital, Royal Oak, Mich.
(principal investigator: R. Ramos, MD; coinvestigators: G. Timmis, MD; V. Gangadharan, MD; S.
Gordon, MD; C. Tollis, RN; and E. Worden, RN);
Yale University, New Haven, Conn. (principal investigator: L.S. Cohen, MD; coinvestigators: C.K. Francis, MD; J. Alexander, MD; D. Copen, MD; M.
Cleman, MD; H. Cabin, MD; M. Remetz, MD; L.
Decklebaum, MD; J. Gerard-Amatruda, RN; D.
Penn, RN; A. Miller, RN; and C. Piselli, RN).
TIMI Phase II Committees
Operations committee: E. Braunwald, MD (chairman), G. Knatterud, PhD; E. Passamani, MD; T.
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Robertson, MD; and R. Solomon, MHS; Executive
committee: E. Braunwald, MD (chairman); B. Chaitman, MD; J. Chesebro, MD; H. Dodge, MD; G.
Knatterud, PhD; K. Mann, PhD; H. Mueller, MD; E.
Passamani, MD; R. Roberts, MD; W. Rogers, MD;
B. Sobel, MD; D. Stump, MD; D.O. Williams, MD;
and B. Zaret, MD; Hemorrhagic event review committee: J. Chesebro, MD (chairman); A. Berke, MD;
E. Bovill, MD; F. Feit, MD; J. Gore, MD; L.D. Hillis,
MD; C. Lambrew, MD; R. Leiboff, MD; J. Markis,
MD; L. Offen, MD; C. Pratt, MD; S. Sharkey, MD;
G. Sopko, MD; and M. Terrin, MD; Mortality and
morbidity classification committee: M. Weisfeldt,
MD (chairman); W. Baker, MD; M. Cowley, MD; K.
Kent, MD; E. Lichstein, MD; T. Robertson, MD; L.
Scherlis, MD; and M. Terrin, MD; Safety and data
monitoring committee: F. Klocke, MD (chairman); J.
Bailar, MD; R. Conti, MD; D. DeMets, PhD; V.
Fuster, MD; T. Killip, MD; H. Roberts, MD; L.
Walters, PhD; Ex-officio members: E. Braunwald,
MD; G. Knatterud, PhD; E. Passamani, MD; and T.
Robertson, MD; Steering committee: members of the
steering committee are the study chairman and the
principal investigators from the TIMI clinical centers,
core laboratories, coordinating center, and National
Heart, Lung, and Blood Institute program office.
References
1. TIMI Research Group: Comparison of invasive and conservative strategies after treatment with intravenous tissue plasminogen activator in acute myocardial infarction: Results of the
Thrombolysis in Myocardial Ischemia (TIMI) II Trial. N Engl
JMed 1989;320:618-627
2. Roberts R, Rogers WJ, Mueller HS, Lambrew CT, Diver DJ,
Smith HC, Willeson JT, Knatterud GL, Forman S, Passamani
E, Zaret BL, Wackers FJT, Braunwald E, for the TIMI
Investigators: Immediate versus deferred 13-blockade following thrombolytic therapy in patients with acute myocardial
infarction: Results of the Thrombolysis in Myocardial Infarction (TIMI) II-B Study. Circulation 1991;83:422-437
3. Gore JM, Sloan M, Price TR, Randall AMY, Boville E, Collen
D, Forman S, Knatterud GL, Sopko G, Terrin ML, TIMI
Investigators: Intracerebral hemorrhage, cerebral infarction,
and subdural hematoma after acute myocardial infarction and
thrombolytic therapy in the Thrombolysis in Myocardial
Infarction Study: Thrombolysis in Myocardial Infarction Phase
II, Pilot and Clinical Trial. Circulation 1991;83:448-459
4. Fleiss JL: Statistical Methods for Rates and Proportions, ed 2.
New York, John Wiley & Sons, Inc, 1989, pp 19-32, 56-82,
165-173
5. Snedecer JW, Cochran WG: Statistical Methods, ed 6. Ames,
Iowa, Iowa State University Press, 1967, pp 91-116
6. Kaplan KL, Meier P: Nonparametric estimation from incomplete observations. JAm Stat Assoc 1958;53:457-481
7. SAS Institute, Inc: sA5 Users Guide: Statistics, ed 5. Cary NC,
SAS Institute, Inc, 1985, pp 401-432, 529-557, 795-800
8. Dixon WJ (ed): BMDP Statistical Software. Berkeley, Calif,
University of California Press, 1985, pp 576-594
9. Harrison DG, Ferguson DW, Collins SM, Skorton DJ, Ericksen EE, Kioschos JM, Marcus ML, White CW: Rethrombosis
after reperfusion with streptokinase: Importance of geometry
of residual lesions. Circulation 1984;69:991-999
10. Schmidt SB, Varghese PJ, Bloom S, Yackee JM, Ross AM:
The influence of residual coronary stenosis on size of infarction after reperfusion in a canine preparation. Circulation
1986;73:1354-1359
11. Williams DO, Ruocco NA, Forman S, TIMI Investigators:
Coronary angioplasty after recombinant tissue-type plasminogen activator in acute myocardial infarction: A report from the
Thrombolysis in Myocardial Infarction (TIMI) Trial. J Am
Coll Cardiol 1987;10:45B-SOB
12. Ellis SG, Roubin GS, King SB III, Douglas JS, Weintraub WS,
Thomas RG, Cox WR: Angiographic and clinical predictors of
acute closure after native vessel coronary angioplasty. Circulation
1988;77:372-379
13. Ellis SB, Roubin GS, King SB III, Douglas JS, Shaw RE,
Stretzer SH, Myer RK: In-hospital cardiac mortality after
acute closure after coronary angioplasty: Analysis of risk
factors from 8,207 procedures. J Am Coll Cardiol 1988;11:
211-216
14. Dalen JE, Gore JM, Braunwald E, Borer J, Goldberg RJ,
Passamani ER, Forman S, Knatterud G, TIMI Investigators:
Six- and twelve-month follow-up of the Phase I Thrombolysis
in Myocardial Infarction (TIMI) Trial. Am J Cardiol 1988;62:
179-185
15. Gruppo Italiano Perlo Studio Della Streptochi-nasi Nell'
infarto Miocardico (GISSI): Long term effects of intravenous
thrombolysis in acute myocardial infarction: Final report of
the GISSI Study. Lancet 1987;2:871-874
16. ISIS-2 Collaborative Study Group: Randomized trial of intravenous streptokinase, oral aspirin, or both or neither among
17,187 cases of suspected acute myocardial infarction: ISIS-2.
Lancet 1988;2:349-360
17. AIMS Trial Study Group: Effect of intravenous APSAC on
mortality after acute myocardial infarction: Preliminary report
of a placebo-controlled clinical trial. Lancet 1:545-549
18. Simoons ML, Betriu A, Col J, von Essen R, Lubsen J, Michel
PL, Rutsch W, Schmidt W, Thery C, Vahanian A, Willems
GM, Arnold AER, de Bono DP, Dougherty FC, Lambertz H,
Meier B, Raynaud P, Ganz GA, Surruys PW, Uebis R, Van de
Werf F, Wood D, Verstraete M: Thrombolysis with tissue
plasminogen activator in acute myocardial infarction: No
additional benefit from immediate percutaneous coronary
angioplasty. Lancet 1988;1:197-202
19. Detre K, Holubkov R, Kelsey S, Bourassa M, Williams D,
Holmes D Jr, Dorros G, Faxon D, Myler R, Kent K, Cowley
M, Cannon R, Robertson T, Coinvestigators of the NHLBI
Percutaneous Transluminal Coronary Angioplasty Registry:
One-year follow-up of the 1985-1986 National Heart, Lung,
and Blood Institute Percutaneous Transluminal Coronary
Angioplasty Registry. Circulation 1989;80:421-428
20. The Veterans Administration Coronary Artery Surgery Bypass
Surgery Cooperative Study Group: Eleven-year survival in the
Veterans Administration randomized trial of coronary artery
bypass surgery for stable angina. N Engl J Med 1984;311:
1333-1339
21. Killip T, Passamani E, Davis K, CASS Principal Investigators
and Associates: Coronary Artery Surgery Study (CASS): A
randomized trial of bypass surgery: Eight years' follow-up and
survival in patients with reduced ejection fraction. Circulation
1985;72(suppl V):V-102-V-109
22. Varnauskas E, European Coronary Surgery Study Group:
Survival, myocardial infarction, and employment status in a
prospective randomized study of coronary bypass surgery.
Circulation 1985;72(suppl V):V-90-V-101
KEY WORDS * acute myocardial infarction * thrombolysis
rt-PA * coronary angioplasty * coronary artery disease
cardiac catheterization
-
One-year results of the Thrombolysis in Myocardial Infarction investigation (TIMI)
Phase II Trial.
D O Williams, E Braunwald, G Knatterud, J Babb, J Bresnahan, M A Greenberg, A Raizner, A
Wasserman, T Robertson and R Ross
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Circulation. 1992;85:533-542
doi: 10.1161/01.CIR.85.2.533
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