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(Circulation. 1995;91:2335-2344.)
© 1995 American Heart Association, Inc.
Articles |
Comparison of Surgical and Medical Group Survival in Patients With Left Main Equivalent Coronary Artery Disease
Long-term CASS Experience
Presented in part at the American College of Cardiology 42nd Scientific Session, Anaheim, Calif, March 16, 1993, and published as an abstract (J Am Coll Cardiol. 1993;21:152A).
From the St Louis (Mo) University Health Sciences Center (E.A.C., G.C.K., B.R.C.); the University of Washington (K.B.D., S.D.C.), Seattle; the National Heart, Lung, and Blood Institute (G.S.), Bethesda, Md; the Mayo Clinic and Mayo Foundation (H.S.), Rochester, Minn; and the University of Alabama Medical Center (H.A.T.), Birmingham.
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Abstract |
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 Top Abstract IntroductionMethods Results Discussion References |
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Background Combined severe proximal left anterior descending and proximal left circumflex coronary artery disease, or left main equivalent (LMEQ) disease, defines a prognostic high-risk angiographic subset of patients with chronic ischemic heart disease. While numerous observational and randomized clinical trials showed prolonged survival in surgically compared with medically treated patients with left main coronary artery disease, relatively few observational studies compared surgical and medical therapies in patients with LMEQ disease. The present report of 912 patients with LMEQ disease in the Coronary Artery Surgery Study (CASS) Registry extends the originally published 5-year surgical and medical group survival analysis to more than 16 years of follow-up and permits analysis of LMEQ patient subgroups.
Methods and Results The CASS Registry contains 912 patients
with LMEQ disease, defined as combined stenoses of 
70% in the
proximal left anterior descending coronary artery before the first
septal perforator and proximal circumflex coronary artery before the
first obtuse marginal branch, initially treated with either surgical or
nonsurgical therapy. The 15-year cumulative survival estimates were
44% for the 630 patients in the surgical group and 31% for the 282
patients in the medical group. Median survival in the surgical group
was 13.1 years (12.7 to 14.1 years, 95% confidence limits) compared
with only 6.2 years (4.8 to 7.9 years) in the medical group
(difference, 6.9 years; P<.0001). Median survival was also
significantly longer in the surgical group stratified by age, sex,
anginal class, left ventricular (LV) function, and coronary anatomy.
However, coronary artery bypass graft (CABG) surgery did not
significantly prolong median survival in patient subgroups with (1)
normal LV systolic function, even if a significant right coronary
artery stenosis (70%) also was present, and (2) mildly abnormal
(LV score, 6 to 10) LV systolic function. The 15-year cumulative
survival in patients with normal LV systolic function in the surgical
and medical groups was 63% and 54%, respectively. Median survival was
>15 years in both the surgical and medical groups (P=NS).
In patients with normal LV systolic function and right coronary artery
stenosis 70%, the 15-year cumulative survival was also similar in
the surgical and medical groups (63% and 53%, respectively). Median
survival was >15 years in both the surgical and medical groups
(P=NS). The 15-year cumulative survival estimates in all
subgroups were affected by convergence of the surgical and medical
group survival curves caused by a disproportionate increase in late
surgical group mortality. Overall, 26% of patients in the medical
group ultimately underwent CABG surgery. If all medical group patients
had survived long enough, about 65% would be estimated to have had
surgery by 15 years. When the CASS Registry patients with LMEQ disease
who participated in the randomized trial or who were randomizable were
analyzed, CABG surgery did not prolong the 15-year cumulative survival
estimates compared with nonsurgical therapy for randomized (71% versus
67%, respectively) and for randomizable patients (62% versus 92%,
respectively) with an LV ejection fraction 50%.
Conclusions This report, which extends follow-up of more than 16
years in CASS Registry patients with LMEQ disease, shows that CABG
surgery prolongs life in most clinical and angiographic subgroups.
However, median survival was not prolonged by CABG surgery in patients
with normal LV systolic function, even if a significant right coronary
artery stenosis (70%) also was present or in patients with an LV
ejection fraction 50% who participated in the CASS randomized trial
or who were randomizable. These results extend our understanding of the
natural history of LMEQ disease and permit a more accurate estimate of
long-term surgical and medical group survival. These long-term results
should allow clinicians to make more informed decisions about the best
choice of treatment available for patients with similar clinical and
angiographic features.
Key Words: coronary disease • bypass • surgery
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Introduction |
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TopAbstractIntroductionMethods Results Discussion References |
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The prognosis for patients with chronic ischemic heart disease is determined primarily by the number of diseased vessels and the left ventric-ular (LV) systolic function,1 2 3 4 5 6 7 8 the severity of their angina pectoris,9 10 and objective indexes of exercise capacity and inducible ischemia.7 11 12 13 The importance of coronary artery bypass graft (CABG) surgery in reducing symptoms, improving quality of life, and increasing exercise tolerance in the majority of patients with significant coronary artery disease who have failed medical therapy is well established.14 In addition, randomized clinical trials showed that CABG surgery prolongs survival compared with medical therapy in patient subgroups who have three-vessel coronary artery disease and an LV ejection fraction of <50%.15 16 17 18 European investigators extended the survival benefit of surgical therapy to patients with three-vessel coronary artery disease and an LV ejection fraction of
50%.19 20 Observational studies directly comparing surgical and medical therapies in patients with significant left main coronary artery disease (LMCD) first showed that CABG surgery lessens symptoms and significantly prolongs survival.21 22 23 24 25 26 Prolonged survival of surgically treated patients compared with those treated medically with LMCD in observational21 22 23 24 25 26 and randomized18 19 20 27 28 29 30 trials prompted investigation into other specific subsets of coronary anatomy. Significant combined disease of the left anterior descending and circumflex coronary arteries proximal to the origin of their major branches, clinically labeled "left main equivalent" (LMEQ) coronary artery disease, has been considered as important as LMCD because of the similar potential degree of myocardial jeopardy from the equivalent stenoses. Although LMEQ disease defines an angiographic high-risk patient subset,31 32 patients with LMEQ disease and LMCD have been reported to have different prognoses.31 32 33 34 35
Prolonged survival in patients with LMEQ disease after CABG surgery
compared with medical therapy has been evaluated in few
trials.33 36 Chaitman et al36 reported
on the
5-year cumulative survival of more than 900 patients with LMEQ disease
in the Coronary Artery Surgery Study (CASS) Registry who were initially
treated with CABG surgery or medical therapy. Overall, CABG surgery
significantly prolonged the 5-year cumulative survival compared with
medical therapy (85% versus 55%, respectively). CABG surgery also
significantly prolonged the cumulative survival in this group of
patients when stratified by important clinical and angiographic
variables. However, when CASS patients with LMEQ disease who
participated in the randomized trial or who were randomizable were
analyzed, CABG surgery did not prolong the 5-year cumulative survival
compared with medical therapy in patients with an LV ejection fraction
of 50%.
The present report extends these initial observations to more than 16 years of follow-up. This is the longest follow-up of the largest cohort of patients with LMEQ disease initially treated with CABG surgery and nonsurgical therapy and is clinically relevant for two reasons. First, a longer duration of follow-up allows for an increased number of events, which then provides greater power to differentiate between treatment groups. Second, the duration of the specific treatment strategy over time can be evaluated and compared with the duration of the therapeutic benefit.
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Methods |
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TopAbstractIntroductionMethods Results Discussion References |
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Patient Population
The CASS Registry, an NHLBI-funded study, contains data from 24 958 patients who underwent coronary angiography for suspected or proven coronary artery disease at 14 participating centers in the United States and one in Canada between 1974 and 1979. The registry contains 912 patients with LMEQ disease, defined as combined stenoses of 70% in the proximal left anterior descending coronary artery before the first septal perforator and proximal circumflex coronary artery before the first obtuse marginal branch, who did not have CABG surgery before enrollment, who had less than 30% left main stenosis, and who had no congenital cardiac abnormalities or concomitant procedures at the time of CABG surgery (ie, aneurysm resection or valve surgery). All registry patients with LMEQ disease, including those who participated in the randomized trial (40 patients) and those who were randomizable (65 patients), are included in the current study report. The 912 patients (282 medical, 630 surgical) are slightly more than the 903 patients (264 medical, 639 surgical) in the previous report,36 primarily because of minor changes in the classification of the CASS database.
Clinical and Angiographic Variables
The definitions of
clinical variables used in the CASS were
described previously.37 Angina pain was classified
according to the Canadian Cardiovascular Society grading system as
follows: class I, chest pain only with prolonged or strenuous exertion;
class II, chest pain with rapid or moderate walking (>2 blocks) or
stair climbing (>1 flight), in cold or wind, or under emotional
stress; class III, chest pain with minimal walking or stair climbing;
and class IV, chest pain with any level of physical activity or even at
rest.38 Unstable angina was defined as angina of recent
onset or crescendo angina within 2 months of angiography or acute
coronary insufficiency. A history of myocardial infarction required
that the patient had been informed by a physician of a definite
infarct. The congestive heart failure (CHF) score included the number
of positive responses (zero to four) to a history of heart failure, use
of diuretic drugs, use of digitalis, and the presence of pulmonary
rales on the admission physical examination.
Coronary angiography was
performed by either the brachial or femoral
technique. Several views of each coronary artery were analyzed. The
extent of arterial stenoses, defined as the maximal percent reduction
in the luminal diameter, was recorded for each of 27 coronary segments.
In this study, combined stenoses of 70% reduction in the luminal
diameter of the proximal left anterior descending coronary artery
before the first septal perforator and the proximal circumflex coronary
artery before the first obtuse marginal branch defined LMEQ disease.
Stenoses of 70% were also considered significant for all other
coronary segments.
Left ventriculography was performed in the 30°
right anterior oblique
view. The left ventriculogram was divided into five segments
(anterobasal, anterolateral, apical, diaphragmatic, and posterobasal).
The systolic contraction of each segment was evaluated visually and
scored numerically as follows: 1, normal; 2, moderate hypokinesis; 3,
severe hypokinesis; 4, akinesis; 5, dyskinesis; and 6, aneurysmal. The
LV score was derived from the sum of the scored segments and was 5 in
patients with normal LV systolic function. The ejection fraction was
calculated by the area-length method39 in 662 patients
with technically adequate LV angiograms. Table 1
summarizes the baseline clinical and angiographic characteristics of
the 630 surgical group patients and the 282 medical group patients.
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CABG Surgery
The surgical techniques and variables in the
CASS were reported
previously.40 41 All patients in the surgical group
received saphenous vein grafts, internal thoracic artery grafts, or
both. The average number of grafts was 3.2±0.9 (SD) per patient. A
left internal thoracic artery graft was used in 16.1% of patients at
the time of their initial surgery. The percent of patients who received
one, two, three, or four or more grafts (distal anastomoses) at the
time of their initial CABG surgery was 1%, 16%, 51%, and 32%,
respectively. Operative mortality, defined as death within 30 days of
surgery, was 3.4%.
Data Acquisition
Follow-up data on each patient were obtained
by a standardized
questionnaire administered at yearly intervals after entry. Detailed
description of the cause of death was obtained for death from 1974 to
1982. As of February 24, 1993, the vital status of 100% of patients
was known. The minimum and maximum range of follow-up at this date was
8.6 and 16.6 years, respectively. In nonsurvivors, the circumstances of
death were determined from hospital records or by telephone interview
with the treating physician or family members.
Assignment to Treatment Group for Analysis
Classification of
registry patients into surgical and medical
groups is not easily defined, a common problem in all published
observational studies.32 Medical group patients were
defined as those who did not undergo CABG surgery or who had late
surgery. In the first year after enrollment, the number of days in
which 95% of the CABG operations were performed was determined for
each hospital (average time, 4 months). Patients who underwent CABG
surgery within this interval or within 90 days after enrollment were
defined as surgical group patients. Survival for surgical group
patients began on the day of surgery. Survival time for medical group
patients was dated from the average time to surgery for the particular
hospital.
The 40 patients with LMEQ disease who participated in the randomized trial were analyzed according to treatment group assignment.
Statistical Considerations
Survival in various subgroups was
computed with Kaplan-Meier
survival curves over 15 years and by calculation of median survival
times. Median survival time was estimated as the time point at which
the Kaplan-Meier survival curves crossed 50%. CIs for medians were
calculated by a nonparametric asymptotic method,42 and
statistical significance was determined by a median test for censored
data.43 The log-rank statistic and the Cox
proportional-hazards model were not used for surgical-medical group
comparisons because the surgical and medical group survival rates
decreased nonproportionally.
The rates of CABG surgery over time after enrollment angiography were estimated by Kaplan-Meier time-to-event analyses. Randomized patients were excluded from the analyses of CABG surgery rates because their assignment to surgery was determined by a random process. Patients who died were removed from the group at risk (censored) at the time of death.
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Results |
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TopAbstractIntroductionMethods Results Discussion References |
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Comparison of Baseline Clinical and Angiographic Characteristics (Table 1
) Of the 912 predominantly male patients with LMEQ disease, 630 (69%) initially underwent CABG surgery, and 282 (31%) were initially treated nonsurgically, a treatment based on physician and patient preferences. Patients in the surgical group had more severe angina (64% class III or IV) compared with the medical group (43%, P<.001). Fewer patients had a history of CHF in the surgical group compared with the medical group (10% versus 26%, P<.0001). Similarly, the mean CHF score was lower in the surgical group compared with the medical group (0.5±0.85 versus 0.97±1.2, P<.0001). Only 4.9% of the surgical group had a CHF score of 3 or 4 compared with 17.4% of the medical group. The surgical group had better LV systolic function (LV score, 8.8; LV ejection fraction, 58.4%) compared with the medical group (11.5, 47.7%; P<.0001).
Long-term Cumulative Survival
The 15-year cumulative survival
of the 630 patients treated with
initial CABG surgery was 44% versus 31% in the 282 nonsurgically
treated patients (Fig 1). The mortality rate in the
surgical group was initially low but gradually increased relative to
the rate in the medical group. Although the magnitude of cumulative
survival difference between the surgical and medical groups was
relatively small after 15 years, the median survival in the surgical
group was 13.1 years (12.7 to 14.1 years, 95% confidence limits)
compared with only 6.2 years (4.8 to 7.9 years) in the medical group
(difference, 6.9 years; P<.0001).
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Influence of Clinical Variables
CABG surgery significantly
prolonged median survival in all
patient subgroups stratified by age, sex, and angina class (Table
2). Advanced age and female sex were associated with
poor survival in the medical group. Median survival was only 4.6 years
in the medical group in patients 65 years of age at the time of
randomization and in female patients (Table 2).
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Influence of Angiographic Variables
LV Function
The 15-year cumulative survival in surgical and medical group
patients was significantly affected by the LV systolic function (Fig
2). The 15-year cumulative survival rates for patients
with normal LV systolic function (LV score, 5) in the surgical and
medical groups were 63% and 54%, respectively; for these patients,
median survival was >15 years in both groups (P=NS) (Table
3). Similarly, the 15-year cumulative survival in
patients with mild impairment of their LV systolic function (LV score,
6 to 10) was 46% in both groups (Fig 2); median survival was
13.8
years in the surgical group and 11.6 years in the medical group
(P=.59) (Table 3).
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However, there were
significant differences in survival for patients
with greater impairment of LV systolic function. The difference in
median survival between the surgical and medical groups increased with
more severe LV dysfunction to 5.0 years for patients with an LV score
of 11 to 14 (P=.0014) and to 6.1 years for patients with an
LV score 15 (both P<.0001) (Table 3). The
patients with
the worst LV function had the poorest prognosis in both treatment
groups; only 22% of surgical group patients and 10% of medical group
patients with severe hypokinesis (LV score 15) were alive after 15
years of follow-up (Fig 2).
Right Coronary
Artery Stenosis
A right-dominant or balanced circulation was present
in 91%
of the surgical group and 95% of the medical group patients. The
15-year cumulative survival (Fig 3) decreased in both
surgical and medical group patients with 70% stenosis of the
dominant or balanced right coronary artery (RCA) (41% and 28%,
respectively); median survival was 13.0 years in the surgical group and
only 4.6 years in the medical group (difference, 8.4 years;
P<.0001) (Table 3). Median survival for LMEQ
disease
patients with RCA stenosis <70% was >15 years in the surgical group
and 10 years in the medical group.
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LV Function and RCA
Stenosis
Patients with a right-dominant or balanced circulation and an
RCA
stenosis 70% had a longer survival if they had normal LV function
(Fig 4). For these patients, the median survival was
>15 years in both groups (P=NS) (Table 3).
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Results in the Randomized CASS Patients
The patients who
participated in the randomized CASS trial
represent a small percent of the CASS Registry with LMEQ
disease (4.4%). To be eligible for the randomized CASS trial, patients
had to meet the following criteria: (1) operable coronary artery
disease, (2) age 
65 years, (3) angina class I or II, (4) LV ejection
fraction 35%, (5) minimum of 3 weeks after a myocardial infarction,
(6) no symptoms of unstable angina for at least 2 months, (7) absence
of concomitant medical illness that would substantially increase
mortality within 5 years of enrollment, and (8) LMCD 70%.
Of the 40
LMEQ disease patients who participated in the randomized
trial (38 had LV ejection fraction data), 29 were randomly assigned to
CABG surgery and 11 to nonsurgical therapy. CABG surgery did not
improve the 15-year cumulative survival compared with nonsurgical
therapy (71% versus 67%, respectively) in these patients with an LV
ejection fraction 50% (Fig 5).
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The 65 randomizable
patients in the CASS Registry with LMEQ disease
fulfilled all inclusion criteria for the randomized trial but were not
randomized because of patient or physician preference (53 had LV
ejection fraction data); 42 randomizable LMEQ disease patients had CABG
surgery and 23 were initially treated nonsurgically. As with the
randomized patients, CABG surgery did not prolong the 15-year
cumulative survival compared with nonsurgical therapy (62% versus
92%, respectively) in these patients with an LV ejection fraction
50% (Fig 6).
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Incremental CABG Surgery
Of patients initially treated
nonsurgically, 26% had at least one
CABG operation at some point during follow-up; 15% of the surgical
group and 3% of the medical group have had more than one CABG
operation (Table 4). Five percent of the surgical group
and 2% of the medical group had coronary angioplasty (Table 4).
After
the first year, about 3.8% of the medical group patients had surgery
each year. If all nonsurgical patients had survived long enough, about
65% would be estimated to have had surgery by 15 years (Fig 7).
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Mortality Analysis
Of the 489 patients who died in the study,
225 had completed
mortality forms. In the surgical and medical groups, 95 and 130 deaths,
respectively, were recorded. Deaths resulting from myocardial
infarction and sudden death occurred more frequently in the medical
group, while noncardiovascular deaths were recorded more frequently in
the surgical group.
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Discussion |
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TopAbstractIntroductionMethods Results Discussion References |
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The present study reports on the longest follow-up of the largest cohort of patients with combined severe proximal left anterior descending and circumflex coronary artery disease. The prognostic importance of significant proximal left anterior descending coronary artery stenoses has been well documented.44 45 46 47 48 49 50 51 In the European Coronary Surgery Study, a lower 6-year cumulative survival was reported for medically treated patients with double-vessel disease, including the proximal left anterior descending artery, compared with medically treated patients with double-vessel disease who did not have proximal left anterior descending artery disease.46 Additionally, both observational and randomized trials showed that for some subgroups of patients with significant proximal left anterior descending artery disease, CABG surgery significantly prolongs survival compared with medical therapy.46 50 52
LMEQ disease defines a high-risk angiographic subset of patients.31 32 Previously published reports suggest that the "equivalence" of prognosis in LMEQ disease to LMCD is an "unproven hypothesis"53 54 55 despite similar clinical and angiographic characteristics in patients with LMCD and LMEQ disease.31 32 34 Hutter54 put forth the concept that the prognostic importance of any coronary stenosis is related to the amount of myocardium in "jeopardy" from an occlusive event. Therefore, although the potential degree of myocardial jeopardy from equivalent degrees of luminal stenoses is similar for LMCD and LMEQ disease patients, their prognoses are thought to be significantly different.
Comparison Between CASS Registry LMEQ and LMCD Patients
Long-term follow-up of CASS Registry LMCD patients is reported
separately.21 Comparisons between CASS Registry LMEQ and
LMCD patients do not control for important clinical and angiographic
variables known to independently affect survival. However, LV systolic
function as assessed both by the LV score and LV ejection fraction and
by the incidence of severe angina (class III or IV) on enrollment in
the registry was similar in the LMEQ and LMCD surgical groups and
medical groups. The 15-year cumulative survival estimates in the LMEQ
and LMCD surgical groups were similar, with an LMCD stenosis severity
stratified by either 50% or 70% (Fig 8). The
15-year cumulative survival estimates in the LMEQ and LMCD medical
groups were similar when an LMCD stenosis severity of 50% was
considered but were significantly lower in the LMCD medical group when
an LMCD stenosis severity of 70% was considered (Fig 8).
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In both LMEQ and LMCD patients, initial CABG surgery improved both
15-year cumulative survival and median survival in most clinical and
angiographic subsets compared with nonsurgical therapy. However, CABG
surgery did not increase survival in either LMEQ or LMCD patients who
had normal LV function (LV score, 5), even if a significant RCA
stenosis (70%) also was present.
Overall, our long-term survival
data comparing two large, stable CASS
Registry databases suggest that the natural histories of LMEQ disease
and LMCD are in fact very similar when compared by treatment group.
However, these results also extend the report of Chaitman et
al32 that 5-year cumulative survival was better in CASS
Registry LMEQ disease patients initially treated medically compared
with CASS Registry LMCD patients initially treated medically when an
LMCD stenosis severity of 70% was considered.
Baseline Characteristics
A greater percentage of patients in
the surgical group had class
III or IV angina. This is not surprising because when the CASS Registry
was initiated in 1974, CABG surgery was an accepted method for
providing relief of ischemic pain syndromes in a substantial majority
of patients with significant coronary artery disease who failed medical
therapy.14 In two CASS Registry studies, improved 5- and
6-year cumulative survival rates were reported in surgically treated
patients with severe angina pectoris (class III and IV) and
three-vessel coronary artery disease.9 10
Nonsurgically treated CASS Registry LMEQ disease patients had a more frequent history of CHF and worse LV systolic function. These data are consistent with a report by Califf et al31 on the clinical presentation and prognostic significance of 282 medically treated LMEQ disease patients.
Angiographic Variables
LV Function
LV systolic
function is an important predictor of survival in
patients with chronic ischemic heart
disease1 2 4 5 6 7 8 15 16 17 18
and in survivors of myocardial infarction.56 In the CASS
Registry, at 12 years of follow-up, medically treated patients with
good LV systolic function (LV ejection fraction 0.50) had cumulative
survival rates of 81%, 70%, and 50% for one-, two-, and three-vessel
disease, respectively.1
LV systolic function is an important predictor of long-term survival in patients with LMEQ disease. Both Califf et al31 and Chaitman et al32 showed by multivariate Cox regression analyses that LV function provides independent prognostic information for medically treated patients with LMEQ disease.
CABG surgery did not
prolong median and long-term survival in LMEQ
disease patients with normal (LV score, 5) or mildly impaired (LV
score, 6 to 10) LV systolic function. In the previous report of CASS
Registry patients with significant LMEQ disease,36
surgical therapy significantly improved the 5-year cumulative survival
compared with medical therapy in patients with an LV ejection fraction
<50% (80% versus 47%, respectively) and in patients with an
ejection fraction 50% (89% versus 74%, respectively), although the
survival benefit was greater in patients with diminished LV
function.
Coronary Pathology
Concurrent RCA
stenosis 70% was present in the majority of
surgical and medical group LMEQ disease patients (83% and 71%,
respectively) on enrollment angiography. Previous reports of patients
with LMEQ disease all show that the majority of patients have
three-vessel
disease.31 32 33 34 35
The highest percentage of
concurrent RCA stenosis 70% was 93%, reported by Tyras et
al33 in their surgically treated LMEQ disease group; the
lowest percentage was 81%, reported by Babb et al.34
Long-term Follow-up
The 15-year cumulative survival in the
912 CASS Registry
patients with LMEQ disease is affected by convergence of the surgical
and medical group survival curves after approximately 8 years, which is
due to a disproportionate increase in the surgical group mortality.
A similar convergence of the surgical and medical group survival curves was also reported and discussed in the CASS Registry LMCD patients.21 Likely explanations for the disproportionate increase in the late surgical group mortality include vein graft conduit attrition and a higher percentage of noncardiovascular deaths in the surgical group.21
Results in the Randomized and Randomizable CASS Patients
As
initially reported in 1986,36 in the subset of
LMEQ disease patients who participated in the randomized CASS trial or
who were randomizable, CABG surgery did not prolong the 5-year
cumulative survival in either group of patients with an LV ejection
fraction 50%. Even at 15 years of follow-up, survival was not
prolonged in the surgical group of CASS Registry LMEQ disease patients
who participated in the randomized trial or who were randomizable.
Medical group survival at 15 years of follow-up in the randomizable
patients was 92%. These data are concordant with a 10-year follow-up
in the CASS randomized trial17 and in randomizable CASS
Registry patients,52 a cohort of relatively young (65
years) patients with class I or II angina pectoris or who were
asymptomatic after myocardial infarction. As a point of comparison, at
10 years of follow-up in the CASS randomized trial,17 in
the subgroup patients with three-vessel coronary artery disease and an
LV ejection fraction 50%, the surgical and medical group survival
rates were 78% and 84%, respectively. In the present study,
despite the small number of CASS Registry LMEQ patients who
participated in the randomized trial (40 patients), survival rates were
76% and 83% for the surgical and medical groups, respectively, at 10
years of follow-up.
Rationale for Surgical-Medical Group Comparisons by Use of Median
Survival
To emphasize important differences in the surgical and
medical
group survival curves, which are often large despite similar survival
estimates at 15 years, we evaluated the 15-year surgical and medical
group survival by comparing the estimated median survival times.
In
this study, the hazard ratio for the surgical group is initially
high for the perioperative period. Then it immediately falls to a low
rate and gradually increases over the 15 years of follow-up. On the
cumulative survival curve (Fig 1), this hazard is reflected by
an
initial decrease in the surgical group survival, which is then followed
by a gradually increasing slope. For the medical group, there is an
initial higher hazard after enrollment angiography (although less than
the hazard associated with CABG surgery), which is then followed by a
constant or slightly decreasing hazard over the 15 years of
follow-up.
Because the hazard for CABG surgery patients is increasing but the hazard for medical group patients is constant or decreasing, these data do not satisfy the proportional-hazards assumption necessary for the log-rank statistic to be easily interpreted or for the Cox survival model to be applicable.
Surgical and Nonsurgical Therapies in the CASS Registry
The
results of CABG surgery and nonsurgical therapy in the CASS
Registry patients with LMEQ disease reflect the prevailing surgical
techniques and medications available between 1974 and 1979 for the
management of chronic ischemic heart disease. Operative mortality was
somewhat higher compared with current standards of practice, and the
current widespread use of the internal thoracic artery has prolonged
long-term graft patency rates compared with saphenous vein graft
conduits.57 58 59 60
Vasodilators and angiotensin-converting
enzyme inhibitors, if available, may have prolonged early medical group
survival because significantly more patients with severe LV systolic
dysfunction were treated
nonsurgically.61 62 63 64 65 66
Coronary angioplasty has become a mainstay for the treatment of
ischemic heart disease in the last decade. While patients with LMEQ
disease are candidates for angioplasty, no published data are currently
available on the long-term efficacy of LMEQ disease angioplasty
compared with either surgical or medical therapies. In a multicenter
trial, sequential Cox proportional-hazards regression analyses showed
that 2-year event-free survival was independently affected by proximal
left anterior descending artery stenoses.44 Recent data
from the Duke University database showed that compared with medical
therapy, CABG surgery improved survival in both two- and three-vessel
disease involving 95% proximal left anterior descending artery
stenosis. However, coronary angioplasty resulted in no survival benefit
compared with medical therapy in patients with single-, double-, and
triple-vessel disease involving 95% proximal left anterior
descending artery stenosis.67
Clinical Implications
Long-term follow-up of CASS Registry
patients with LMEQ disease
extends the reported 5-year survival data that CABG surgery prolongs
life in most patient subgroups with LMEQ disease. However, median
survival was not prolonged by CABG surgery in the following patient
subgroups: (1) normal LV systolic function, even if an RCA stenosis
70% also was present; (2) mildly abnormal (LV score, 6 to 10) LV
systolic function; and (3) CASS Registry LMEQ disease patients with an
LV ejection fraction 50% who participated in the randomized trial or
who were randomizable. Contrary to some previous reports, women treated
with CABG surgery experienced prolonged survival similar to men.
Uncontrolled observations of CASS Registry LMEQ and LMCD patients suggest that the natural histories of the two registry cohorts are similar when compared by treatment group and support the original hypothesis of an "equivalence" between LMEQ disease and LMCD.
Both CABG surgery and coronary angioplasty currently are used to treat LMEQ disease. Ongoing clinical trials will provide data on the long-term safety and efficacy, comparing CABG surgery with coronary angioplasty in the near future. CABG surgery, however, remains the primary revascularization strategy to prolong survival and improve quality of life in patients with significant LMEQ disease.
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Acknowledgments |
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This work was supported by research contracts from the NHLBI, Bethesda, Md.
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Footnotes |
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Reprint requests to Kathryn B. Davis, PhD, CASS Coordinating Center, University of Washington, 107 NE 45th St, Room 530, Seattle, WA 98105.
Received August 10, 1994; revision received November 7, 1994; accepted November 20, 1994.
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