Download Twenty-Year Survival After Coronary Artery Surgery

Twenty-Year Survival After Coronary Artery Surgery
An Institutional Perspective From Emory University
William S. Weintraub, MD; Stephen D. Clements, Jr, MD; L. Van-Thomas Crisco, MD;
Robert A. Guyton, MD; Joseph M. Craver, MD; Ellis L. Jones, MD; Charles R. Hatcher, Jr, MD
Background—Coronary artery bypass graft (CABG) surgery has been performed frequently for symptomatic coronary
atherosclerotic heart disease for more than 30 years. However, uncertainty exists regarding the relationship between
long-term survival after CABG and readily available clinical correlates of mortality.
Methods and Results—We studied outcome at 20 years by age, sex, and other variables in 3939 patients who had CABG
surgery from 1973 to 1979 in the Emory University System of Healthcare. Twenty-year survival, freedom from
myocardial infarction, and freedom from repeat CABG were 35.6% (95% confidence interval [CI], 33.9% to 37.3%),
66.6% (95% CI, 64.6% to 68.6%), and 59.1% (95% CI, 56.9% to 61.5%). Multivariate correlates of late mortality were
age (hazard ratio [HR], 1.46 per 10 years), female sex (HR, 1.21), hypertension (HR, 1.44), angina class (HR, 1.07 per
class increase of 1), prior CABG (HR, 1.72), ejection fraction (HR, 1.07 per 10-point decrease), number of vessels
diseased (HR, 1.11 per 1-vessel increase), and weight (HR, 1.04 per 10 kg). Twenty-year survival by age was 55%, 38%,
22%, and 11% for age ⬍50, 50 to 59, 60 to 69, and ⬎70 years at the time of initial surgery. Survival at 20 years after
surgery with and without hypertension was 27% and 41%, respectively. Similarly, 20-year survival was 37% and 29%
for men and women.
Conclusions—Symptomatic coronary atherosclerotic heart disease requiring surgical revascularization is progressive with
continuing events and mortality. Clinical correlates of mortality significantly impact survival over time and may help
identify long-term benefits after CABG. (Circulation. 2003;107:1271-1277.)
Key Words: coronary disease 䡲 surgery 䡲 survival 䡲 mortality
C
oronary atherosclerotic heart disease remains the number
one cause of death, disability, and economic loss among
industrialized nations. Although the primary focus of care for
patients with atherosclerosis is prevention of disease progression by risk factor modification, management strategies for
symptomatic patients include both pharmacological therapy
and revascularization by either percutaneous coronary intervention or coronary artery bypass graft (CABG) surgery.
CABG surgery was introduced nearly 35 years ago,1 and it
has become clear that this operation relieves angina pectoris
and likely improves quality of life.2– 4 Long-term survival
after CABG surgery in prospectively evaluated patient groups
has been ⬇33% at 15 years5 and 20% at 22 years,6 although
the numbers of patients reported is limited. Because CABG is
one of the most commonly performed and costly surgical
interventions performed today, it is important to understand
the impact of age and associated patient-specific disease
characteristics on survival.
This study describes survival and the natural course of
disease in a patient population undergoing coronary artery
surgery for standard indications from 1973 to 1979, with both
short and long-term follow-up. This is the largest such cohort
of patients from one institution reported to date that assesses
the impact of age and associated disease correlates (hypertension, congestive heart failure, diabetes mellitus, prior
myocardial infarction, and angina severity) on survival over
such a long time span. We found age was the most significant
contributor to mortality over time. As the number of associated mortality correlates increased, long-term survival decreased dramatically.
Methods
Definitions
Single-vessel disease was defined as ⱖ50% diameter luminal narrowing in either the left anterior descending, left circumflex, or right
coronary artery or a major branch or branches. Double-vessel disease
was the presence of ⱖ50% diameter luminal narrowing in 2 of the 3
major epicardial vessel systems. Three-vessel disease was the presence of ⱖ50% diameter luminal narrowing in all 3 major epicardial
vessel systems or in the left anterior descending and proximal
Received October 18, 2002; revision received November 26, 2002; accepted November 26, 2002.
From the Division of Cardiology, Department of Medicine (W.S.W., S.D.C., L.V.-T.C.), and the Division of Cardiothoracic Surgery, Department of
Surgery (R.A.G., J.M.C., E.L.J., C.R.H.), Emory University School of Medicine, Atlanta, Ga.
Presented in part at the 72nd Scientific Sessions of the American Heart Association, Atlanta, Ga, November 7–10, 1999, and published in abstract form
(Circulation. 1999;100(suppl I):I-93.)
Correspondence to William S. Weintraub, MD, Professor of Medicine, Emory Center for Outcomes Research, 1256 Briarcliff Road, Suite 1N, Atlanta,
GA 30306. E-mail [email protected]
© 2003 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org
DOI: 10.1161/01.CIR.0000053642.34528.D9
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March 11, 2003
TABLE 1.
Clinical Characteristics by Sex
Women
(n⫽627)
Men
(n⫽3312)
P
57⫾9
54⫾9
⬍0.0001
226 (50.9) (n⫽444)
809 (34.8) (n⫽2325)
⬍0.0001
Prior MI. n (%)
227 (50) (n⫽454)
1334 (54.8) (n⫽2436)
0.07
Age, y
Systemic hypertension, n (%)
Diabetes, n (%)
84 (19.1) (n⫽440)
261 (11.3) (n⫽2302)
⬍0.0001
Heart failure, n (%)
28 (6.7) (n⫽417)
104 (4.8) (n⫽2156)
0.14
Class III/IV angina, n (%)
127 (58) (n⫽219)
493 (51.7) (n⫽954)
0.11
7 (1.1)
24 (0.7)
0.44
Prior CABG, n (%)
Weight, kg
65⫾13 (n⫽445)
81⫾12 (n⫽2291)
⬍0.0001
Ejection fraction, %
62⫾13 (n⫽487)
58⫾13 (n⫽2544)
⬍0.0001
⬍0.0001
1-Vessel disease, n (%)
152 (28.0)
561 (19.8)
2-Vessel disease, n (%)
180 (33.2)
929 (32.8)
3-Vessel disease, n (%)
155 (28.6)
1028 (36.3)
0.0007
Left main disease, n (%)
55 (10.1)
313 (11.1)
0.58
Elective surgery, n (%)
0.9
568 (91)
3046 (92)
0.28
Q-wave MI, n (%)
21 (3.37) (n⫽624)
152 (4.68) (n⫽3249)
0.18
Death in hospital, n (%)
7 (1.12) (n⫽625)
32 (0.98) (n⫽3273)
0.91
10.07⫾9.72
8.9⫾6.58
Length of stay, d
0.0002
Values are mean⫾SD or n (%). MI indicates myocardial infarction.
circumflex arteries in left-dominant patients. Left main disease was
the presence of ⱖ50% diameter luminal narrowing in the left main
coronary artery. An emergent procedure was a procedure performed
in the setting of acute ischemia or infarction. Myocardial infarction
as a complication after the procedure was determined by the
development of new Q waves. Variables defined by patient history
were hypertension, diabetes, severity of angina, congestive heart
failure, prior myocardial infarction, and myocardial infarction during
follow-up. Angina was classified by the Canadian Cardiovascular
Society Classification.7 Congestive failure was classified by New
York Heart Association criteria.8
Patient Population and Surgical Methods
Demographics, clinical characteristics, and coronary angiography
data on patients undergoing cardiac surgery in the Emory University
Hospital System have been prospectively collected and entered into
a computerized database since 1972. The population for the present
study was composed of 3939 consecutive patients with ischemic
heart disease entered into the Emory Cardiac Surgery Database
between 1973 and 1979. All fields were defined in a data dictionary.
CABG standard surgical techniques, extracorporeal circulation,
and myocardial protection methods consistent with practice at that
time were used.9
Patient Follow-Up
Follow-up information was obtained from patients or referring
physicians. Follow-up status for each end point was also assessed at
each subsequent hospital admission. Patients not readmitted were
contacted by telephone or letter approximately every 5 years.
Follow-up was available on 3905 of 3939 patients (99%). The
median length of follow-up was 14.2 years and, in survivors, 20
years. Information obtained included occurrence of myocardial
infarction since the initial CABG, subsequent need for an additional
revascularization procedure (percutaneous coronary intervention or
CABG), death (cardiac plus noncardiac), and recurrent angina. All
follow-up information was recorded on standardized forms and
entered into the computerized database. All repeat procedures
performed at Emory University Hospitals were confirmed from the
database. Myocardial infarctions during follow-up were ascertained
largely from the patients, and there may be inherent under-reporting
and over-reporting.
Statistical Analyses
Data are expressed as proportions or as mean⫾SD. Differences in
categorical variables were analyzed by ␹2 or Fisher’s exact tests, and
differences in continuous variables were analyzed by ANOVA.
Multivariate correlates of long-term survival were determined by
Cox model analysis. Missing data were filled in using the method of
Harrel.10 Discrimination of the multivariate analysis for in-hospital
and long-term mortality models were examined using the C index.
Validation and calibration of models were tested by the methods of
Harrel.10 Potential nonlinear effects of each of the continuous
predictor variables were checked using restricted cubic splines.
Interaction terms were examined. Statistical modeling and testing
were performed in S-Plus.
Results
Clinical Characteristics and Outcome by Sex
Baseline clinical and angiographic characteristics of the 3939
patients studied are presented in Table 1. Women, who
represented 16% of the study population, were older (57⫾9
versus 54⫾9 years) and had a higher prevalence of hypertension and diabetes and more severe angina. However, women
had fewer prior myocardial infarctions, better ejection fractions, and more single-vessel and less triple-vessel coronary
artery disease. The presence of clinical congestive heart
failure, double-vessel coronary artery disease, and left main
disease was essentially the same among in both men and
women. There was no difference noted in the acuteness of the
procedure. There was little difference in in-hospital outcome,
with Q-wave myocardial infarctions and death (1.12% for
women, 0.98% for men) nearly equal in the 2 groups; length
of stay was longer among women (10.1⫾9.7 versus 8.9⫾6.6
days; P⫽0.0002).
Weintraub et al
TABLE 2.
Survival After CABG
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Clinical Characteristics by Age
Age Group
⬍50 y (n⫽1066)
50 – 60 y (n⫽1692)
60 –70 y (n⫽1038)
⬎70 y (n⫽143)
P
44⫾5
55⫾3
64⫾3
72⫾2
⬍0.0001
115 (10.8)
245 (14.5)
227 (21.9)
40 (28)
⬍0.0001
Systemic hypertension, n (%)
255 (33.4) (n⫽763)
438 (37.9) (n⫽1155)
289 (39.8) (n⫽727)
54 (43.5) (n⫽124)
0.03
Prior MI, n (%)
421 (52.5) (n⫽802)
661 (54.7) (n⫽1209)
411 (54.6) (n⫽753)
68 (54) (n⫽126)
0.79
Age
Female sex, n (%)
Diabetes, n (%)
74 (9.8) (n⫽756)
134 (11.7) (n⫽1146)
119 (16.6) (n⫽716)
18 (14.5) (n⫽124)
0.0006
Heart failure, n (%)
25 (3.5) (n⫽709)
60 (5.6) (n⫽1076)
35 (5.2) (n⫽671)
12 (10.3) (n⫽117)
0.01
Class III/IV angina, n (%)
124 (47) (n⫽264)
246 (50.6) (n⫽486)
186 (55.4) (n⫽336)
65 (74.7) (n⫽87)
0.0001
Ejection fraction, %
59⫾13 (n⫽812)
59⫾13 (n⫽1280)
60⫾14 (n⫽811)
59⫾14 (n⫽128)
0.22
Prior CABG, n (%)
Weight, kg
7 (0.7)
17 (1)
6 (0.6)
1 (0.7)
0.60
81⫾14 (n⫽765)
79⫾13 (n⫽1147)
75⫾12 (n⫽721)
71⫾12 (n⫽103)
⬍0.0001
1-Vessel disease, n (%)
274 (30.1)
272 (19.1)
150 (16.6)
17 (12.6)
⬍0.0001
2-Vessel disease, n (%)
283 (31.1)
504 (35.4)
279 (30.9)
42 (31.1)
0.06
3-Vessel disease, n (%)
291 (31.9)
509 (35.7)
336 (37.2)
48 (35.6)
0.11
Left main disease, n (%)
63 (6.9) (n⫽911)
139 (9.8) (n⫽1424)
138 (15.3) (n⫽903)
28 (20.7) (n⫽135)
⬍0.0001
Values are mean⫾SD or n (%). MI indicates myocardial infarction.
Clinical Characteristics by Age Group
Patients stratified by age are shown in Table 2. Patients age
50 to 59 years represented the largest number of patients
(1692 patients; 43%), and the fewest were ⬎70 years (143
patients; 3.6%) at the time of initial operation. At each
increasing age group of 10 years (⬍50, 50 to 60, 60 to 70, and
ⱖ70 years), men outnumbered women, although the proportion of women in each age group increased with each decade,
as did the prevalence of hypertension, diabetes, heart failure,
class III/IV angina, and left main coronary artery disease.
Hospital Outcome by Age Group
Table 3 shows surgical status and early clinical outcome
grouped according to age. The prevalence of elective, emergent, and urgent CABG, as well as post-surgical Q-wave
myocardial infarction, was roughly preserved across age
categories. Only death in the hospital and length of stay
significantly increased with age. Mortality rates rose most
dramatically across the age groups (0.09% for ages ⬍50 years
to 2.11% for ages ⬎70 years). Older patients also had longer
hospital stays. No significant age-adjusted effects were seen
among elective, emergent, or urgent CABG procedures.
Correlates of Long-Term Mortality
Consistent with prior studies assessing clinical correlates of
late outcome among patients undergoing surgery 20 years
TABLE 3.
ago,11,12 we found age (Table 4) was the most powerful
contributor to decreased survival probability in our model
(hazard ratio, 1.46 per decade of life); the younger the patient
at the time of operation, the higher the likelihood of long-term
survival. Hypertension, female sex, and prior coronary surgery were also powerful contributors to decreased survival
likelihood. Other risk factors included higher initial angina
class, reduced ejection fraction, number of vessels diseased,
and increased weight. Although the presence of diabetes or
heart failure contributed univariately to mortality risk, neither
showed independent statistical significance. The ability of the
model to discriminate was at best moderate, with a c index of
0.631 (validated at 0.630). The calibration of the model was
excellent (data not shown). A separate model was also
developed with all patients surviving beyond 5 years censored at 5 years. In this model, sex and weight were no longer
independent risk factors. Otherwise, the model was similar,
with the same correlates and similar hazard ratios, 95%
confidence intervals, and probability values.
Survival by Correlates
Overall survival at 1, 5, 10, 15, and 20 years was 97.6% (95%
CI, 97.1 to 98.0), 91.9% (95% CI, 91.5% to 92.4%), 78.4%
(95% CI, 77.1% to 79.8%), 56.5% (95% CI, 54.8% to
Outcome by Age
Age Group
⬍50 y (n⫽1066)
50 – 60 y (n⫽1692)
60 –70 y (n⫽1038)
⬎70 y (n⫽143)
P
Elective
966 (91)
1564 (92)
954 (92)
130 (91)
0.39
Emergent
59 (5.53)
65 (3.84)
43 (4.14)
6 (4.2)
0.19
Urgent
41 (3.85)
63 (3.72)
41 (3.95)
7 (4.9)
0.91
Q-wave MI
54 (5.15) (n⫽1048)
78 (4.7) (n⫽1661)
37 (3.62) (n⫽1022)
4 (2.82 (n⫽142)
0.26
Death in hospital
1 (0.09) (n⫽1056)
19 (1.14) (n⫽1672)
16 (1.56) (n⫽1028)
3 (2.11) (n⫽142)
0.003
8.83⫾7.01
8.82⫾6.32
9.61⫾8.56
10.35⫾7.16
0.002
Length of stay
Values are mean⫾SD or n (%). MI indicates myocardial infarction.
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TABLE 4.
Correlates of Long-Term Mortality
Age (per 10 years)
HR
95% CI
PI
1.46
1.38 to 1.55
⬍0.0001
Female sex
1.21
1.06 to 1.39
0.006
Hypertension
1.17
1.09 to 1.25
⬍0.0001
Angina class (per 1-class increase)
1.07
1.01 to 1.12
0.011
Prior CABG
1.72
1.11 to 2.65
0.014
Ejection fraction (10% decrease)
1.07
1.04 to 1.10
⬍0.0001
No. of vessels diseased (per vessel)
1.11
1.06 to 1.16
⬍0.0001
Weight (per 10 kg)
1.05
1.01 to 1.08
0.0081
HR indicates hazard ratio; CI, confidence interval. C index is 0.631 (validated
at 0.630).
58.2%), and 35.6% (95% CI, 33.9% to 37.3%), respectively.
Survival by age group over time is seen in Figure 1. Survival
curves by age begin to diverge around 7 years after surgery,
and divergence increases significantly at 10 years and beyond. Ten years after surgery, percent survival in each age
group was 85%, 80%, 74%, and 56% for ages ⬍50, 50 to 60,
60 to 70, and ⬎70 years at the time of initial operation.
Twenty years after surgery, percent survival was 51%, 38%,
22%, and 11% for age ⬍50, 50 to 60, 60 to 70, and ⬎70
years, respectively.
Survival to 20 years was 29% in women and 37% in men
(P⬍0.0001; Figure 2). Survival in patients without hypertension was 41%, and in patients with hypertension, 27%
(P⬍0.0001). Survival to 20 years was 40% for patients with
ejection fractions ⬎50%, 25% for ejection fractions 35% to
50%, and 17% for patients with ejection fractions ⬍35%
(P⬍0.0001; Figure 3).
Freedom From Events
Overall 20-year freedom from myocardial infarction and
freedom from repeat CABG were 66.6% (95% CI, 64.6% to
68.6%) and 59.1% (95% CI, 56.9% to 61.5%), respectively.
Freedom from subsequent myocardial infarction was 57% at
⬍50 years, 68% at 50 to 60 years, 74% at 60 to 70 years, and
77% at ⬎70 years. The inverse age relationship is probably
related to the higher mortality with increasing age. Freedom
from subsequent CABG is shown in Figure 4. Like the
analysis of freedom from subsequent myocardial infarction,
freedom from either surgical or percutaneous revascularization was greatest among older age groups. Ten years after
initial CABG surgery, 79%, 87%, 94%, and 99% of patients
aged ⬍50, 50 to 60, 60 to 70, and ⬎70 years, respectively
were free from repeat CABG. At 20 years, 47%, 58%, 74%,
and 92% of patients aged ⬍50, 50 to 60, 60 to 70, and ⬎70
years were free from repeat CABG. Twenty-year freedom
from percutaneous coronary intervention was 69%, 73%,
80%, and 91%, respectively, for patients aged ⬍50, 50 to 60,
60 to 70, and ⬎70 years.
Discussion
In the present study, we showed in a large sample of 3939
patients that there are continuing events over the 20 years
after coronary surgery. Mortality at 20 years is high. The
ability to determine who is at especially high risk was at best
moderate, with a C index of 0.63. Variables that have often
been shown to predict mortality, such as age and ejection
fraction, were predictive in this population. Others, especially
diabetes, were not independently predictive. This may reflect
the fact that this study was drawn from a population ⬎20
years ago and the spectrum of patients undergoing coronary
surgery today may be somewhat different.
Several studies have considered long-term survival to 20
years after coronary surgery. Laurie et al11 studied the
outcome of 1698 patients undergoing CABG between 1968
and 1975. Survival at 20 years was 40% for 1-vessel, 26% for
2-vessel, 20% for 3-vessel, and 25% for left main disease.
Independent correlates of survival were age at operation,
extent of coronary disease, left ventricular function, history of
Figure 1. Twenty-year survival after coronary surgery by age group.
Weintraub et al
Survival After CABG
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Figure 2. Twenty-year survival after coronary surgery by sex.
stroke, and preoperative heart failure. In a much smaller
study, Ulicny et al12 studied the 20-year outcome of 100
patients undergoing CABG between 1970 and 1972. The 5-,
10-, 15-, and 20-year survival rates were 89.8%, 68.4%,
53.1%, and 40.8%, respectively. Myers et at5 evaluated
15-year follow-up after CABG in 8221 patients from the
Coronary Artery Surgery Study (CASS) registry, with a mean
follow-up of 15 years. Survival was 90% at 5 years, 74% at
10 years, and 56% at 15 years. Female sex, small body
surface, ischemic symptoms, and emergency status predicted
early mortality. Heavier weight, prior myocardial infarction,
diabetes, smoking, left main and left anterior descending
artery stenosis, and use of vein grafts only increased late
mortality.
Registries and randomized trials of patients undergoing
CABG have provided a great deal of information regarding
continued patient benefit from this intervention in appropriately
selected patients.13–17 Patients with left main disease and
3-vessel disease have improved survival compared with patients
treated medically.2– 4 Technical improvements have resulted in
reduced perioperative mortality, myocardial infarction, and
stroke, as well as better long-term survival and improved graft
patency with internal thoracic artery grafting and improved
myocardial protection.18,19 More recently, off-pump surgery has
resulted in shorter lengths of stay and possibly improved
outcome.20 Despite these improvements, the disease remains
chronic and unremitting. Clearly, risk factor control must remain
a cornerstone of long-term therapy.
Figure 3. Twenty-year survival after coronary surgery by ejection fraction.
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March 11, 2003
Figure 4. Twenty-year freedom from
repeat CABG by age group.
The dramatic impact of age on survival in cohorts of
patients undergoing surgical and percutaneous revascularization has been extremely consistent.21 However, the impact of
associated mortality correlates on survival varies considerably. One would expect that the effect of age on mortality
might be partially accounted for by other risk factors associated with the aging process, such as higher prevalence of
diabetes mellitus, 3-vessel coronary artery disease, systemic
hypertension, and congestive heart failure. Diabetics have a
higher rate of myocardial infarction and need for additional
revascularization procedures and a lower (although acceptable) survival after successful CABG.22 The number of
coronary arteries severely narrowed has been shown to
increase in-hospital and long-term mortality. A history of
hypertension and heart failure has also been associated with
adverse early and long-term outcomes after CABG.22
Study Limitations
This study has some limitations. We used multivariate analysis to reduce confounding in determining the increased risk
associated with several variables. However, there may be
additional risk factors that affect outcome that we have not
controlled for that could have influenced our results. One of
these is the influence of the period of observation, because
patients included in this study were operated on ⬎20 years
ago, and outcomes reflect the surgical and medical approaches prevalent at that time. There have been substantial
improvements in surgical techniques and preoperative and
postoperative care that have reduced perioperative mortality
and morbidity.23 Routine use of internal mammary grafts
were not common at that time, and their use has likely
increased graft conduit patency and subsequent survival, both
short and long term.18 Furthermore, the additive benefit of
routine antiplatelet and lipid-lowering therapy in this patient
population would also likely have improved the benefits of
CABG surgery significantly. These caveats notwithstanding,
our in-hospital complication rates were excellent for that time
period, as are the long-term outcomes compared with other
reports.5,11,12
Conclusions
Finally, these data serve to remind clinicians that symptomatic coronary atherosclerotic heart disease requiring revascularization is progressive, with continuing events and mortality. Age and associated clinical disease characteristics
(survival risk factors) heavily impact survival after CABG.
Hypertension, hyperlipidemia, and other modifiable diseases
should be treated aggressively because they are associated
with decreased survival over time. Furthermore, the longterm benefits of surgical coronary revascularization were
short lived among those patients with multiple clinical correlates for decreased survival, including older age, even
among a surgical population that was significantly healthier
than today’s coronary surgery population.24
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