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(Circulation. 1995;92:1101-1109.)
© 1995 American Heart Association, Inc.
Articles |
Effect of Infarct Artery Patency on Prognosis After Acute Myocardial Infarction
From the Mount Sinai Medical Center, Miami Beach, and the University of Miami (Fla) School of Medicine (G.A.L.); the University of Missouri Hospitals and Medical School, Columbia (G.F.); the Brigham and Women's Hospital and Harvard Medical School, Boston, Mass (G.M., M.A.P., E.B.); the University of North Carolina School of Medicine, Chapel Hill (S.C.S.); Georgetown University Hospital and Medical School, Washington, DC (B.J.G.); the University of Texas Health Sciences Center, Houston (C.-C.W., L.M.); the University of Texas Southwestern Medical Center, Dallas (J.D.R.); and the Montreal Heart Institute (J.L.R.).
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Abstract |
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 Top Abstract IntroductionMethods Results Discussion References |
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Background In patients with acute myocardial infarction (MI), early restoration of patency of the infarct-related artery (IRA) leads to preservation of left ventricular function and improved clinical outcome. However, there is evidence that the benefits associated with a patent IRA are out of proportion to the observed improvement in ventricular function and may result not only from salvage of ischemic myocardium but also from the opening of the IRA beyond a narrow postinfarct time window. The objectives of this study were (1) to assess the effect of IRA patency on outcome of patients after acute MI with left ventricular dysfunction while controlling for differences in left ventricular ejection fraction and the extent of coronary disease and (2) to determine the effect of angiotensin-converting enzyme (ACE) inhibitor therapy on patients with patent as well as occluded infarct arteries.
Methods and Results The Survival and Ventricular
Enlargement (SAVE) study consisted of 2231 patients with a documented
MI and a left ventricular ejection fraction 
40%. They
were randomized to the ACE inhibitor captopril (50 mg TID)
or placebo 3 to 16 days after MI and were followed for an average of
3.5 years. Left ventricular ejection fraction, measured
with radionuclide left ventriculography, was repeated at the end of the
follow-up period. The 946 patients in whom the patency of the IRA was
established before randomization form the basis of this study. At
cardiac catheterization averaging 4.2 days after
infarction, 30.7% of patients had an initially occluded IRA. After
revascularization, 162 of the 946 patients (17.1%)
were left with an occluded IRA at the time of randomization. The 162
patients with persistently occluded IRAs and 784 with patent IRAs had
similar clinical baseline characteristics, but those with occluded
arteries had a slightly lower ejection fraction than the 784 patients
with patent infarct arteries (30% versus 32%, P=.01). Cox
proportional-hazards analyses showed that the independent
predictors of all-cause mortality were hypertension (relative risk
[RR] 1.94, P<.001), number of diseased coronary
arteries (RR 1.68, P<.001), occluded IRA (RR 1.49,
P=.039), ejection fraction (RR 1.36, P<.001),
age (RR 1.10, P=.030), and use of ß-adrenergic receptor
blocking agents (RR 0.60, P=.007). Independent predictors of
a composite end point consisting of cardiovascular
mortality, morbidity, or reduction of ejection fraction of 
9 units
were occluded IRA (odds ratio [OR] 1.73, P=.002),
hypertension (OR 1.71, P<.001), number of diseased vessels
(OR 1.38, P<.001), ejection fraction (OR 1.18,
P=.003), use of ß-adrenergic receptor blocking agents (OR
0.67, P=.007), and randomization to captopril (OR 0.70,
P=.009).
Conclusions IRA patency within 16 days after MI predicts a favorable clinical outcome, independent of the number of obstructed coronary arteries or of left ventricular function. The beneficial effect of ACE inhibition is independent of patency status of the IRA. These findings support the need for additional, prospective clinical trials of late reperfusion in MI patients.
Key Words: myocardial infarction • arteries • captopril • ventricles • receptors, adrenergic, beta
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Introduction |
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TopAbstractIntroductionMethods Results Discussion References |
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It is well established that early thrombolytic therapy leads to better left ventricular function and survival in patients with acute myocardial infarction (MI).1 2 3 4 This beneficial effect occurs presumably through the prompt restoration of patency of the infarct-related artery (IRA) and the salvage of jeopardized, ischemic myocardium. Some experimental evidence5 6 7 and clinical observations8 9 10 11 12 13 14 15 16 17 18 also suggest that the benefits of establishing patency of the IRA are not restricted to a narrow postinfarction time window of myocardial salvage. However, there is no clear consensus that a patent IRA is beneficial in patients with completed MI independent of left ventricular function. Although it has been demonstrated that the administration of an angiotensin-converting enzyme (ACE) inhibitor improves the long-term outcome of patients with MI and left ventricular dysfunction19 20 and that ß-adrenergic receptor blocking agents also improve the outcome of post-MI patients,21 22 23 it is not clear whether these beneficial effects are independent of IRA patency.24
The objectives of the present prospectively designed study, carried out on patients with a completed MI and significant residual left ventricular dysfunction, were to (1) assess the effect of IRA patency on clinical outcome while controlling for differences in left ventricular ejection fraction, the extent of coronary artery disease, and other important baseline clinical characteristics; (2) to determine the effect of ACE inhibitor therapy on patients with patent as well as occluded infarct arteries; and (3) to determine whether the benefit of ß-adrenergic receptor blocking agents was independent of IRA patency.
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Methods |
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TopAbstractIntroductionMethods Results Discussion References |
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The Survival and Ventricular Enlargement (SAVE) trial was a double-blind, randomized multicenter trial that tested the hypothesis that chronic therapy with the ACE inhibitor captopril enhances survival and clinical outcome in survivors of acute MI (AMI) with left ventricular dysfunction. Patients were 21 to 80 years old and had a radionuclide left ventricular ejection fraction
40%. Potentially eligible patients underwent
catheterization if they had recurrent ischemia
or a positive exercise test. Randomization to placebo or captopril
occurred 3 to 16 days after a documented AMI. After randomization to
placebo or captopril (to a maximum dose of 50 mg TID), patients were
followed for 2 to 5 years (mean, 3.5 years). All surviving patients
underwent a repeat left ventricular ejection fraction
measurement during the last months of follow-up. Complete aspects of
protocol design as well as the final results of the SAVE study have
been published.19 25 The SAVE Cardiac
Catheterization Core Laboratory was established before
the beginning of SAVE, and an analysis of the importance of
infarct artery patency was a prespecified ancillary study. The
present study focuses on the effect of infarct artery patency on
the following end points: (1) total or all-cause mortality, (2)
cardiovascular mortality, and (3)
cardiovascular mortality or morbidity. This combined end point is a prespecified SAVE study end point that includes the development of severe heart failure requiring hospitalization or the use of an open-label ACE inhibitor, recurrent MI, or a drop in LV ejection fraction of 9 points or greater at the end of the study compared with the measurement of ejection fraction taken at the beginning of SAVE.
Although SAVE did not restrict or mandate specific aspects of management that occurred between the qualifying MI and randomization, if patients had unstable postinfarct angina or low-threshold ischemia, cardiac catheterization was required before randomization. These requirements, as well as clinical preferences across centers, led to a clinically directed cardiac catheterization being obtained between the qualifying MI and randomization in 1301 of the 2231 patients. Moreover, if catheterization identified a need for revascularization therapy, SAVE required that such revascularization be completed before randomization. Thus, this management strategy guaranteed that, at randomization, SAVE patients did not have active or easily provoked ischemia.
Analysis of Coronary Arteriograms
Participating SAVE Centers
submitted 990 angiograms from these
1301 patients for inclusion in this analysis. Three
cardiologists in the SAVE Cardiac Catheterization Core
Laboratory who were experienced in invasive procedures (G.A.L., G.F.,
S.S.) analyzed these 990 angiograms. Coronary arteries
were analyzed on the basis of standard, multiple-view
angiograms. Multiple segments (proximal, mid, and distal) in each
coronary artery and bypass graft were analyzed
according to the angiographic analysis scheme published by the
Coronary Artery Surgery Study.26 Each individual
coronary artery segment was measured by digital electronic
caliper and analyzed for percent reduction in luminal diameter
and antegrade and collateral flow as described below.
Definitions of IRA Occlusion
Infarct location was defined
electrocardiographically by the
SAVE ECG Core Laboratory. In patients with anterior infarctions, the
left anterior descending coronary artery was defined as the
IRA. In patients with inferior or posterior infarctions,
the IRA was defined as either the left circumflex or the right
coronary artery, whichever was occluded or more severely
narrowed on the angiogram. Occlusion of the IRA required the presence
of grade 0 or 1 antegrade flow and grade 0 or 1 collateral flow as
defined by the TIMI investigators.27 The patency status of
the IRA was further modified by the results of
revascularization performed between the SAVE MI and
randomization. Patients who underwent percutaneous
transluminal coronary angioplasty of the IRA before
randomization had the patency status redefined on the basis of final
results of the angioplasty. Patients with occluded IRAs who underwent
successful surgical bypass of an occluded IRA before randomization were
considered to have patent IRAs.
Forty-nine patients with indeterminate MI locations and 3 patients with incomplete coronary angiograms were excluded from the analysis. This led to a cohort of 938 patients (990 minus 52 patients) with known IRA status before revascularization and 946 patients after coronary bypass surgery was performed on 8 patients with indeterminate infarct locations (938 plus 8). All subsequent analyses were carried out on these 946 patients.
Analysis of Left Ventriculograms
The decision to perform left
ventriculography as part of the
catheterization procedure was based on clinical
indications and local practice in each catheterization
laboratory and was not protocol-determined. Left ventriculography was
performed and quantitatively analyzed in 674 of the 946
patients (71.2%). The presence and extent of mitral
regurgitation were graded on a standard scale (0 to
4).28 The left ventriculograms at end diastole
and at end systole were traced and digitized. When extrasystoles were
present, care was taken to analyze a cardiac cycle at least
two beats after the last extrasystole. Computer-assisted
analysis of the traced left ventriculograms provided (1) left
ventricular volumes calculated by the area-length
method29 in the 411 patients in whom calibration for
magnification correction was available; (2) determination of left
ventricular shape by use of the sphericity
index,30 an index of overall left ventricular
shape based on calculating ventricular volume and dividing
it by a hypothetical spherical volume generated by using the longest
axis of the left ventricle as the diameter of a sphere (calculation of
the sphericity index does not require correction for magnification);
and (3) analysis of wall motion by the centerline
method31 ; the percentages of the diastolic
left ventricular circumference that were dyskinetic or
akinetic, hypokinetic, and normal were calculated.
Statistical Analyses
The analysis of baseline characteristics
in mutually
exclusive categories was examined by 
2
statistics, and continuous variables were compared by one-way
ANOVA. The univariate analysis of end points by
infarct artery status was performed with the Cox proportional-hazards
model.32 Multivariate analyses to
determine whether infarct artery status, captopril therapy, and
ß-adrenergic receptor therapy were independent predictors of
all-cause mortality and cardiovascular mortality were
performed with this same method, controlling for important clinical
covariates. A logistic regression analysis33 was
used to analyze the composite end point. Survival curves were
generated by the Kaplan-Meier method.34 Curves were
generated by univariate as well as
multivariate methods to correct for the effects of
other covariates.35
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Results |
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TopAbstractIntroductionMethods Results Discussion References |
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Baseline Characteristics
The 946 patients in whom the IRA status was known and who form the basis for this analysis were compared with the other 1285 patients in the SAVE trial (Table 1
). The former
were in general at lower risk; they were younger, had a higher left
ventricular ejection fraction, were less likely to be
diabetic or to have experienced a previous MI, and were less likely to
have pulmonary congestion during the index (SAVE) infarction
than were the patients who were not catheterized. In addition, they
were more likely to have received thrombolytic therapy and
to have undergone mechanical revascularization.
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Initial Management of the IRA
Cardiac catheterization was
carried out between
the day of infarction and 16 days after infarction (mean, 4.2 days;
median, 3.0 days). At baseline, before myocardial
revascularization, 288 of the 938 patients (30.7%)
in whom the IRA had been identified had an occluded IRA. Patients who
had not received thrombolytic therapy were more likely to
demonstrate occluded IRAs at the baseline cardiac
catheterization before surgical or
transcatheter revascularization than
were patients who had received thrombolysis (184 of 494
[37.2%] versus 104 of 444 [23.4%], P<.001). Of
these
288 patients with an initially occluded IRA, 130 had
revascularization leading to a patent IRA
(coronary angioplasty, 101; coronary bypass, 25; and
coronary bypass after unsuccessful angioplasty, 4), and an
occluded IRA persisted in 158. An initially patent IRA was observed in
650 patients. Coronary angioplasty was performed in 165
patients. In 6 (3.6%), angioplasty of an initially patent IRA led to
an occluded IRA. In 2 of these 6 patients, IRA patency was restored by
coronary bypass operations. Thus, 4 patients with
postangioplasty IRA occlusions were added to the 158 patients with
nonrevascularized IRA occlusions. An additional 8 patients with
indeterminate MI locations and indeterminate status of the IRA had
multivessel coronary bypass graft surgery and were therefore
reclassified as having a patent IRA. These procedures led to the final
group of 946 patients for analysis; 162 (17.1%) had an
occluded and 784 (82.9%) a patent IRA at the time of randomization
into SAVE.
Comparison Between Patients With Patent and Occluded IRAs
Patients with occluded or patent IRAs were similar in age, sex
distribution, and important clinical baseline variables to patients
with patent IRAs (Tables 2 and 3).
However, patients with occluded IRAs were significantly less likely to
have sustained a Q-wave anterolateral MI and to have received
thrombolytic therapy than patients with a patent IRA, and
they had slightly lower baseline radionuclide left
ventricular ejection fractions than did patients with a
patent IRA. Coronary angiography revealed that patients with
occluded IRAs were more likely to have three-vessel coronary
disease (occluded versus patent: 46 of 162, 28.4%, versus 149 of 784,
19.0%; P=.027).
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Although there were no significant
differences between the two groups
with regard to left ventricular volumes (Table 3
), patients
with occluded IRAs had a more spherical systolic left
ventricular shape. Patients with occluded IRAs also were
more likely to have mitral regurgitation on left
ventriculography.
Patient Outcomes
During the follow-up, which ranged from 2 to
5 years and averaged
3.5 years, patients with occluded IRAs demonstrated higher unadjusted
all-cause mortality (occluded versus patent, 24% versus 14%;
P<.001) and cardiovascular mortality
(occluded versus patent, 23% versus 12%; P<.001) than did
patients with patent IRAs (Table 4, Fig 1). The
prespecified composite end point
occurred more frequently in patients with occluded than patent IRAs
(51% versus 37%, P<.001).
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Multivariate Analyses
An occluded IRA was an independent
predictor of all-cause
mortality, cardiovascular mortality, and the composite
"unfavorable cardiovascular outcome" end point.
The components of the multivariate analyses are
detailed in Table 5 and Fig 2.
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Effect of Captopril
In the subset of 946 patients who form
the basis of this
analysis, randomization to captopril was not an independent
predictor of survival as it was for the total SAVE
cohort.14 However, randomization to captopril did show a
significant, independent effect in reducing the incidence of the
composite end point of cardiovascular mortality or
morbidity. Patients with a patent IRA who were randomized to captopril
had a composite end point incidence of 34.3%; the incidence of this
end point was intermediate in patients with a patent IRA who were
randomized to placebo and in patients with an occluded IRA who were
randomized to captopril (38.8% and 40.2%, respectively); patients
with an occluded IRA randomized to placebo had the highest event rate
(62.7%) (Table 5 and Fig 3).
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Effect of ß-Adrenergic Receptor Blockade
Of 784 patients
with patent IRAs, 299 (38.1%) were taking
ß-adrenergic receptor blocking agents before randomization. Of 162
patients with occluded IRAs, 64 (39.5%) were taking ß-adrenergic
receptor blocking agents before randomization.
Multivariate analyses demonstrated that
patients taking ß-adrenergic receptor blocking agents were less
likely than those not taking these agents to have clinical end points
independent of IRA patency (Table 5).
Analysis of Patients With Occluded IRAs Undergoing
Revascularization
The effect of revascularization on the outcome
of patients with an initially occluded IRA was tested by comparing the
baseline characteristics and eventual outcome of 130 patients who
underwent successful revascularization
(angioplasty, 101; unsuccessful angioplasty followed by
coronary bypass, 4; and coronary bypass alone, 25) with
those of 158 patients with persistent occlusion of the IRA. (This
latter number excludes 4 patients with an initially patent IRA that was
later occluded after unsuccessful angioplasty.) There were no
significant differences in the patients' age or sex, other risk
factors, assignment to captopril therapy, and baseline coronary
anatomy; however, patients with an initially occluded IRA that
was opened did have a significantly higher ejection fraction but a
lower overall use of ß-adrenergic receptor blocking agents than did
those patients whose IRAs were not successfully opened (Table
6). Although the difference in ejection fraction between
groups was small, there were large differences favoring the
revascularized group in the incidence of all-cause mortality,
cardiovascular mortality, and the combined end
point.
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Discussion |
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TopAbstractIntroductionMethods Results Discussion References |
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The patency status of the IRA after coronary occlusion is a function of the balance between spontaneous and pharmacologically induced lysis of intracoronary thrombi and of mechanical revascularization on the one hand and of resistance to lysis and spontaneous reocclusion of patent arteries on the other. Therefore, depending on the nature of the patient population, the therapy given, and the timing of catheterization, different investigators have found widely varying patency rates of IRAs.8 36 37 The present study, based on the subgroup of 946 of the 2231 SAVE patients in whom patency status at randomization was known, found 17.1% of patients with occluded IRAs. The principal objective of these analyses was to determine the long-term effects of the actual patency status of the IRA in patients who had recently sustained a documented MI resulting in significant left ventricular dysfunction and who did not have residual active or easily provokable ischemia.
Recent studies have emphasized that in patients with acute MI, early attainment of a patent infarct artery is associated with improved left ventricular function,38 and they support the well-established concept that early myocardial reperfusion limits myocardial necrosis and thereby reduces mortality.39 However, the hypothesis tested by the present study, ie, that a patent IRA improves clinical outcome independent of left ventricular function, has not been tested prospectively. There are, however, retrospectively obtained clinical data that support this idea. Cigarroa et al10 reviewed 179 patients catheterized 1 month after MI and followed for an average of 47 months. Although the ejection fraction at 1 month did not appear to be influenced by the patency status of the IRA, patients with occluded infarct arteries experienced a total mortality of 18%, in sharp contrast to the 0% in patients with a patent infarct artery. Schroder et al12 addressed these questions in patients with AMI enrolled in a trial of thrombolytic therapy. Patients who had demonstrated no evidence of early reperfusion, based on the presence of late-peaking creatine kinase curves, were catheterized 1 month after AMI. The long-term survival of patients with patent infarct arteries was better than would have been expected on the basis of the difference in ejection fraction of the patent and occluded-artery groups. Similarly, Galvani et al18 retrospectively assessed patients with Q-wave infarctions and reported that infarct artery patency and end-systolic volume were independent predictors of survival. Other data reported by the Western Washington study8 and reviewed elsewhere9 13 14 also support the concept that the improvement in survival after thrombolysis is greater than would be expected from the observed improvement in ejection fraction alone.
Large multicenter trials such as the Second International Study of Infarct Survival,2 the LATE study,40 and the meta-analysis provided by the Fibrinolytic Therapy Trialists' Collaborative Group4 have shown that patients receiving thrombolytic therapy beyond the usual time window in which salvage of myocardium might be expected to occur (>6 hours after the onset of symptoms) and who may be presumed to have a higher IRA patency rate than patients who did not receive a thrombolytic intervention experienced improved survival. However, these studies provided no direct information regarding IRA patency or left ventricular function, and we cannot infer from them that late IRA patency is an independent predictor of clinical outcome.
The present study differs from prior studies in that (1) it was designed prospectively at the time the SAVE Catheterization Core Laboratory was conceived in 1988, and an analysis of the importance of infarct-artery patency was a prespecified ancillary study end point; (2) the analysis was restricted to patients with completed infarctions, documented left ventricular dysfunction, and no clinically overt ischemia or heart failure at randomization; (3) patients in whom a variety of different strategies led to the final patency status of the IRA were included, more accurately reflecting present clinical practice; (4) the coronary anatomy and baseline as well as follow-up ejection fractions were available in all patients; and (5) corrections for initial differences in left ventricular function and other baseline variables were made. We observed that patients with patent IRAs had a significantly better prognosis than did patients with occluded arteries. After adjustment for differences in baseline characteristics, including ejection fraction, the patency status of the IRA remained an independent predictor of all-cause mortality, cardiovascular mortality, and the composite end point consisting of cardiovascular mortality, morbidity, and serious reduction of left ventricular ejection fraction.
There are several possible mechanisms by which the patency status of the IRA may affect postinfarct survival independently of myocardial salvage and postinfarction left ventricular function. Jeremy et al41 and Pfeffer et al42 demonstrated that an occluded IRA is associated with greater increases in left ventricular volume, known to be an important predictor of long-term mortality in postinfarction patients.43 Within 1 month of an anterior Q-wave acute MI, patients with occluded IRAs have been shown to have greater left ventricular volumes and more spherical left ventricles than do patients with a patent infarct artery, despite minor differences in ejection fraction.16 44 Topol et al45 administered tissue plasminogen activator or placebo to 197 patients with 6 to 24 hours of symptoms and ST elevations. Left ventricular volumes were assessed by contrast left ventriculography. Placebo patients demonstrated a small but significant increase in left ventricular volume. Patients receiving thrombolysis did not have any change in left ventricular volumes. Nidorf et al17 used quantitative echocardiography to study patients who had undergone coronary reperfusion at different times after MI; those with occluded IRAs demonstrated progressive left ventricular dilatation. However, 13 patients with late coronary angioplasty of an occluded IRA an average of 5 days after infarction demonstrated early dilatation but a later trend toward normalization of left ventricular size. In the present study, the measurement of left ventricular volumes was limited to a single early point in time, and therefore, this study cannot determine whether the measurable clinical benefit of a patent infarct artery is due to prevention of left ventricular remodeling.
The patency status of the IRA may also affect the incidence of postinfarct arrhythmia and thereby prognosis. Patients with occluded IRAs are more likely to demonstrate late potentials46 47 as well as inducible ventricular tachycardia48 49 and therefore to be at higher risk of sudden death. Patients with patent IRAs may also have hibernating myocardium50 51 in proximity to the infarct, whose viability is maintained by the patent vessel. Although it does not contribute to left ventricular performance, hibernating myocardium might be less subject to dyskinesis and deformation than transmurally infarcted myocardium and thereby may reduce left ventricular remodeling and lead to a more favorable outcome.
The presence of mitral regurgitation after acute MI has been reported to be a predictor of poor outcome.52 This study found that patients with occluded IRAs have more spherical left ventricles during end systole and are more likely to have mitral regurgitation. These associated findings suggest that IRA occlusion is associated with subtle geometric alterations in left ventricular shape, which may have functional consequences. In turn, the presence of mitral regurgitation in patients with occluded IRAs may contribute to their poorer prognosis.
Effect of ACE Inhibition and ß-Adrenergic Receptor
Blockade
Several
investigators39 53 54 have demonstrated
that
therapy with ACE inhibitors attenuates left
ventricular volume enlargement after MI. The most prominent
effect of captopril in attenuating left ventricular volume
enlargement occurred in patients who had occluded IRAs.42
An important objective of the present study was to determine
whether the clinical benefits of postinfarction captopril therapy are
dependent on the patency status of the infarct artery.
The SAVE trial demonstrated that the ACE inhibitor reduced all-cause mortality in postinfarct patients with impaired left ventricular function.19 The present analysis, based on a subset of the patients in SAVE, had limited statistical power and did not demonstrate the significant reduction in all-cause mortality that was observed in the overall SAVE trial. However, the event rate and statistical power were higher when the prospectively defined composite end point of cardiovascular mortality, morbidity, and a marked deterioration of left ventricular function was used. This composite end point provided sufficient statistical power to demonstrate that randomization to captopril was an independent predictor of improved overall clinical outcome (RR for the combined end point in patients randomized to captopril, 0.70; P<.001). The finding that ACE inhibitor therapy and IRA patency are independent predictors of clinical outcome suggests that the previously described benefits of ACE inhibition in the total SAVE population may be extended to the subgroups with patent as well as occluded IRAs.
Glamann et al24 reported that patients with an occluded IRA who were taking ß-adrenergic receptor blocking agents had a markedly better prognosis (2% cardiac mortality over 4 years) than did patients with an occluded IRA who were not taking ß-adrenergic receptor blocking agents (30% cardiac mortality). Thus, the present study attempted to ascertain whether the benefit of postinfarct ß-adrenergic receptor blockade was present in patients with a patent IRA. Although the use of ß-blockade in the SAVE study was clinically determined and not randomized, multivariate analyses clearly demonstrated that ß-blockade is beneficial independent of IRA patency and independent of captopril therapy.
Effect of Revascularization of an Initially
Occluded IRA
Although the use of revascularization
therapies in patients whose baseline angiograms demonstrated an
initially occluded IRA was clinically determined and not randomized,
striking differences in clinical outcomes were demonstrated between the
revascularized and nonrevascularized groups. Indeed, these differences,
which included a halving of long-term mortality, occurred in the
setting of a minor, two-point difference in ejection fraction between
groups. Thus, this subgroup analysis underscores the importance
of IRA patency, even when patency has not been spontaneously achieved
but rather is the result of revascularization
therapies.
Limitations of the Present Study and Conclusions
The effects
of the patency status of the IRA in post-MI patients
would optimally be studied by determining coronary
arterial patency early after infarction, excluding patients
who required revascularization on clinical grounds,
randomizing the remaining patients with occluded arteries to mechanical
revascularization or no
revascularization, and restudying patients weeks or
months later to reassess coronary arterial patency.
The present analyses of nonrandomized patients fall short
of this idealized study, since the 946 patients in whom the patency
status of the IRA was established and on whom this analysis is
based were not selected at random. Furthermore, a single
coronary angiogram between the day of infarction and up to 16
days later may misclassify the ultimate chronic patency status of the
infarct artery, since it cannot take into account either spontaneous
late reperfusion or spontaneous asymptomatic late
reocclusion. Nevertheless, despite this imperfect methodology, the
baseline features of these 946 patients, including left
ventricular function, were well characterized, and the
results observed are relevant to this population, which is
representative of a large fraction of patients with
acute MI and moderately depressed left ventricular function
(Table 1). From the analysis of these patients, we may conclude
that both patency of the IRA and treatment with the ACE
inhibitor captopril are independent predictors of favorable
clinical outcome in patients with MI and left ventricular
dysfunction.
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Acknowledgments |
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The SAVE study was funded by a grant from the Bristol Myers Squibb Institute for Pharmaceutical Research. The authors gratefully acknowledge the expert secretarial assistance provided by Lori Martens.
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Footnotes |
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Reprint requests to Gervasio A. Lamas, MD, Division of Cardiology, Mount Sinai Medical Center, 4300 Alton Rd, Miami Beach, FL 33140.
Received January 11, 1995; accepted February 28, 1995.
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References |
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