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Ann Thorac Surg 2005;79:1563-1569
© 2005 The Society of Thoracic Surgeons

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Original articles: Cardiovascular

Late Outcome After Stenting or Coronary Artery Bypass Surgery for the Treatment of Multivessel Disease: A Single-Center Matched-Propensity Controlled Cohort Study

Thoraxcenter, Erasmus Medical Center, Rotterdam, The Netherlands

Accepted for publication November 17, 2004.

^_* Address reprint requests to Dr van Domburg, Erasmus Medical Center, Thoraxcenter, Room H539, Dr Molewaterplein 40, 3015 GD Rotterdam, The Netherlands (E-mail: r.vandomburg{at}erasmusmc.nl).

	Abstract

Top Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
BACKGROUND: Although several randomized controlled trials examined the relative benefits of coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI), the most appropriate treatment remains a matter of debate, at least in some subsets of patients. Therefore, we evaluated the 8-year outcome after multivessel stent implantation (stent group) or coronary artery bypass surgery (CABG group) in a single-center propensity-matched cohort study.

METHODS: The stent study population consisted of all 409 consecutive patients who underwent an elective coronary intervention between 1995 and 1999 in whom at least 2 stents were implanted in multiple vessels. They were matched by using the propensity score method with 409 CABG patients of 1,723 CABG patients with multivessel disease who underwent elective CABG in the same period of time. The two populations were very different before matching. After matching, the CABG population resembled a stent population.

RESULTS: The cumulative survival rates after stent were 93%, 90%, and 82% at, respectively, 3, 5, and 8 years; and after CABG 97%, 93%, and 87% (p = 0.02). This was caused mainly by patients with left main disease (p = 0.03). Event-free survival was only 70%, 68%, and 64% after stent and 89%, 82%, and 78% after CABG at, respectively, 3, 5, and 8 years (p < 0.0001). After adjusting, stent was an independent predictor of higher mortality.

CONCLUSIONS: In this matched cohort study with an 8-year follow-up, survival was better and less repeat revascularizations were needed among patients undergoing elective CABG for the treatment of multivessel disease as compared with the stent group.

	Introduction

Top Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
Coronary artery bypass grafting (CABG) was introduced in 1968 and rapidly became a routine operation for patients with coronary artery disease [1]. Percutaneous coronary intervention (PCI) was introduced into clinical practice almost 10 years later in 1977 and was initially considered appropriate only for patients with single-vessel disease [2]. However, as experience and technology have advanced, the procedure is nowadays also used routinely in patients with multivessel disease.

In the last decade, several randomized controlled trials examined the relative benefits of CABG and PCI in patients with single or multivessel coronary artery disease. Yet, the most appropriate treatment remains a matter of debate at least in some subsets of patients [3–7]. Although fewer patients undergoing CABG require repeat revascularizations, several studies found no difference in survival [8–10]. Only recently, a meta-analysis showed a survival benefit in favor of CABG in patients with multivessel disease up to 8 years of follow-up [11]. Nevertheless, subsequent improvements in both percutaneous and surgical techniques rapidly outdate the validity of any conclusion that may have been drawn from the earlier studies. Reevaluation may be especially important in the case of PCI since the recent recognition that coronary stents have consistently improved the outcomes of patients treated percutaneously up to 1 year [12, 13]. However, the 8-year outcome results of these trials are still awaited. Also their applicability to all patients requiring invasive treatment of coronary artery disease is debatable. The aim of this propensity score matched cohort study was to describe the 8-year outcome after initial multivessel stent implantation (stent group) or multivessel CABG surgery in a series of patients treated in a single center.

	Patients and Methods

Top Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
In our institution, all patients referred for coronary intervention are discussed in a team consisting of cardiothoracic surgeons and interventional cardiologists, and the most appropriate treatment is chosen. The study complies with the Declaration of Helsinki and was approved by the Medical Ethical Committee. Informed consent has been obtained from all patients.

Stent Population
The stent study population consisted of all 553 patients between January 1995 and December 1999 in whom coronary revascularization was accomplished with multiple stenting in at least two vessels. Excluded were patients with previous CABG (n = 54) and renal impairment (n = 20). Other reasons for exclusion were patients with an acute myocardial infarction in the 24 hours before stent (n = 45) and urgent procedures (n = 48). After exclusion, the stent study population consisted of 409 consecutive patients

CABG Population
The CABG study population consisted before matching of 1,911 patients who were referred to undergo CABG in the same span. Fifty-three patients with prior CABG and 136 not elective patients were excluded. The same exclusion criteria that were applied to the stent group were used. This resulted in the exclusion for renal impairment (n = 68). Additionally, rescue CABG patients for failed stent (n = 14) were also excluded. After exclusion, but before the matching, the CABG study population consisted of 1,640 consecutive patients. By using the propensity score method, 409 CABG patients were matched [14].

Methods for Propensity Scoring Matching
Because of the substantial differences in baseline characteristics between the treatment groups, propensity score methodology was used to identify comparable patients treated with different strategies. The propensity score was initially proposed by Rosenbaum and Rubin and has been used in prior observational studies to help adjust for treatment selection bias [15–17].

First, a propensity score for each patient was constructed, providing an estimate of the propensity toward belonging to one treatment group versus the other, This was done by performing multiple logistic regression with the endpoint the type of intervention (CABG coded as 0, stent as 1). All factors that might be predictive of receiving either intervention were evaluated. These included age, sex, prior myocardial infarction, prior angioplasty, unstable versus stable angina, diabetes, dyslipidemia, hypertension, three- versus two-vessel disease, left main disease, and ejection fraction (normal, moderate, or reduced or poor). The patient characteristics before the matching according to 409 stent patients and 1,640 CABG patients are shown in Table 1. The two study populations were far from similar, with the most striking difference of the 80% three-vessel disease rate in the CABG population and only 23% in the stent population. To obtain improved insight in the differences, patients were divided into four quartiles according to their propensity score (Table 2). A large difference was observed between the quartiles: almost two thirds (63%) of the stent patients were in the lowest quartile and only a very few (2%) in the highest quartile, whereas the CABG patients were more equally divided among all quartiles.

Statistical Methods
Continuous data were expressed as mean value ± SD and were compared using Student's t test, and categorical variables by ² tests. The level of significance was a p value of less than 0.05 (two-tailed). Cumulative survival curves were constructed using the Kaplan-Meier method. Among patient subgroups the log-rank test was used to compare survival curves. A stepwise multivariate Cox analysis was carried out with the use of baseline clinical, characteristics and procedure-related variables in order to identify independent predictors of 5-year survival and event-free survival. Preselected variables were age, sex, diabetes (defined as pharmacologically treated, type I or II), treated hypertension, treatment for dyslipidemia, number of diseased vessels (stenosis >50%; two-vessel disease or three-vessel disease), qualitative left ventricular ejection fraction (normal if >55%; reduced if >45% and <55%, and moderate if >30% and <45%), chronic obstructive pulmonary disease (pharmacologically treated), and renal impairment (serum creatinine >150 mmol/L). Myocardial infarction and stroke were diagnosed by discretion of the treating physician.

	Results

Top Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
Stent Patients
During the stent procedure, on average 2.3 stents were implanted with an average total length of 48 mm (Table 4). In 78%, lesions in the right coronary artery were stented; in 73%, in the left anterior descending artery; and in another 67%, in the left circumflex artery. In 43% of the patients, IIB/IIA inhibitors were used.

Mortality, Myocardial Infarction, and Stroke
During the in-hospital period, 4 patients died in the stent group and 1 patient died in the CABG group. During 8-year follow-up an additional 52 patients in the stent group and 44 patients in the CABG group died, of whom 82% and 71%, respectively, died of a presumed cardiac cause. The cumulative survival rates after stent were 93%, 90%, and 82% at, respectively, 3, 5, and 8 years; and after CABG, they were 97%, 93%, and 87% (p = 0.02; Fig 1A). Most of this difference was due to the patients with left main disease and poor left ventricular function (p = 0.03; Fig 1B).

View larger version (28K): [in this window] [in a new window]   Fig 1. Cumulative survival of 409 multivessel disease patients undergoing an elective percutaneous coronary angioplasty (pci) with multiple stent placement in multiple vessels, and 409 multivessel disease patients undergoing a first elective coronary bypass surgery (cabg): (a) in the total population and (b) in patients with left main disease (CABG, n = 61; stent, n = 61).

Figure 2 shows the cumulative event-free survival (freedom from the combined endpoints death, myocardial infarction, stroke, and coronary revascularization) rates after stent and CABG. After 1 year, both curves run parallel. The CABG patients had a better event-free survival compared with patients treated by stent. Cumulative event-free survival was 70%, 68%, and 64% after stent at, respectively, 3, 5, and 8 years; and, respectively, 89%, 82%, and 78% after CABG (p < 0.0001).

View larger version (12K): [in this window] [in a new window]   Fig 2. Cumulative survival and cumulative major adverse cardiac events-free survival (death, myocardial infarction, stroke, and coronary revascularization) in 409 multivessel disease patients undergoing an elective percutaneous coronary angioplasty (pci) with multiple stent placement in multiple vessels, and 409 multivessel disease patients undergoing a first elective coronary bypass surgery (cabg).

	Comment

Top Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
This study was designed to describe stent and CABG as elective treatment strategies in propensity-matched patients with multivessel disease at a single center and to evaluate the applicability and generality of results of randomized comparison to clinical practice. Patients were treated in daily clinical practice according to the prevailing "best practice" at our center at the time.

At 8 years, we found that in our study patients who underwent CABG had a better survival compared with those who were treated with stent. At the end of the follow-up, the cumulative mortality rate for stent was 18%, and only 13% for CABG. This is consistent with a recent meta-analysis from Hoffman and associates [11] showed a survival benefit in two- and three-vessel disease for CABG surgery versus stenting up to 8 years of follow-up. Unfortunately, the study of Hoffman was not based on individual patient data. Jones and colleagues [18] found in the Duke registry that patients with three-vessel disease and patients with two-vessel disease with at least 95% left anterior descending stenosis benefited from bypass surgery versus angioplasty. However, in the randomized ARTS trial no differences in mortality could be established between stent and CABG [12]. Important to mention is that almost all of the beneficial survival effect of CABG in our study is due to inclusion of patients with left main disease in the propensity score matching procedure. According to the American College of Cardiologists/American Hospital Association guidelines, these patients ought to be referred to surgery and most clinical trials therefore exclude these patients. However, in our clinical practice about 60 (15%) of these patients were treated by angioplasty.

All patients treated by stent had multivessel stent implantation, and compared with balloon angioplasty, an improved late clinical outcome could reasonably be expected. Several studies have demonstrated the superiority of coronary stenting compared with balloon angioplasty [19–21]. It is evident that the use of stents has improved long-term clinical outcome. The need for repeat revascularization decreased in our center from 33% after balloon angioplasty to about 23% using bare metal stents [22]. Routine use of drug-eluting stents, recently reported to be associated with minimal occurrence of short-term restenosis, is expected to improve clinical outcome after stent even more [23, 24].

Compared with the matched CABG population, the need for repeat revascularization was still significantly higher in the stent group and mainly occurred in the first year. The rate of additional procedures in the stent group at 1 year (19.8%) was lower than the rate of 33.7% reported in the meta-analysis of other trials. Most of this difference accounts for the fact that this meta-analysis included studies since 1987; and especially in the early 1990s, restenosis rates were high. Also, the 1.7% rate for patients assigned to CABG was also slightly lower than the reported rate of 3.3% [11]. Of the patients assigned to stent, 8% subsequently underwent CABG. Although repeat revascularization after CABG is infrequently needed up to 8 years, progress of coronary disease and vein graft attrition may become a clinical problem after 8 to 10 years [22].

Limitations
This study has some important limitations. First, the study is not a randomized clinical trial but an observational study of a propensity-matched cohort. Because all patients were initially screened for the optimal treatment, the majority of the CABG patients were mostly regarded less suitable for percutaneous coronary intervention. Given the 76% incidence of two-vessel disease after the matching, this selection does not represent the usual distribution of multivessel disease treated with surgical intervention, which is 80% three-vessel disease in our institution. As can be seen in Tables 1 and 2, the stent and original CABG populations differed greatly, and by using the propensity score matching procedure, the resulting matched CABG cohort ultimately resembled the stent cohort.

According to the guidelines, patients with left main disease should be referred to CABG. However, our stent population consisted of 61 patients (15%) with left main disease, which accounts for 18% (279 patients with left main disease underwent CABG) of all patients. Unfortunately, we were not able to retrieve the exact reason for the choice for stent, but we may assume that most of these patients were contraindicated for CABG.

There may have been a selection bias such that we did not adequately control for some unknown variable that increased the probability of undergoing stent or CABG and the probability of short- and long-term adverse outcomes. We used a propensity score to control for treatment selection bias. The propensity score method controls for group differences more extensively than any method previously used to compare outcomes for coronary intervention (stent and CABG). Nevertheless, unknown factors, such as possibly a presently not existing coronary artery extent score, may affect treatment choice and were not used in the model and may have resulted in some selection bias. The propensity score methodology ideally comprises all factors that are known to be predictive of treatment selection.

In conclusion, in this propensity-matched cohort, patients with multivessel disease who underwent CABG had a better survival and fewer repeat revascularizations as compared with the stent patients.

	Acknowledgments

Top Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
The support of Marijke Rozema-Botermans with the data collection is highly appreciated. This study would not have been possible without the kind support of many general practitioners.

	References

Top Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 

1. Favaloro RG. Saphenous vein autograft replacement of severe segmental coronary artery occlusion: operative technique Ann Thorac Surg 1968;5:334-339.[Medline]
2. Grüntzig AR, Senning A, Siegenthaler WE. Nonoperative dilatation of coronary-artery stenosis: percutaneous transluminal coronary angioplasty N Engl J Med 1979;301:61-68.[Abstract]
3. The BARI Study Group Comparison of coronary bypass surgery with angioplasty in patients with multivessel diseaseThe Bypass Angioplasty Revascularisation Investigation (BARI) Investigators. N Engl J Med 1996;335:217-225.[Abstract/Free Full Text]
4. The CABRI Study Group First-year results of CABRI (Coronary Angioplasty versus Bypass Revascularisation Investigation) Lancet 1995;346:1179-1184.[Medline]
5. Hamm CW, Reimers J, Ischinger T, et al. A randomized study of coronary angioplasty compared with bypass surgery in patients with symptomatic multivessel coronary diseaseGerman Angioplasty Bypass Surgery Investigation. N Engl J Med 1994;331:1037-1043.[Abstract/Free Full Text]
6. King III SB, Lembo NJ, Weintraub WS, et al. A randomized trial comparing coronary angioplasty with coronary bypass surgeryEmory Angioplasty versus Surgery Trial. N Engl J Med 1994;331:1044-1050.[Abstract/Free Full Text]
7. The RITA Study Group Coronary angioplasty versus coronary artery bypass surgery: the Randomized Intervention Treatment of Angina (RITA) trial Lancet 1993;341:573-580.[Medline]
8. The BARI Study Group Seven-year outcome in the Bypass Angioplasty Revascularisation Investigation (BARI) by treatment and diabetic status J Am Coll Cardiol 2000;35:1122-1129.[Abstract/Free Full Text]
9. King III SB, Kosinski AS, Guyton RA, et al. Eight-year mortality in the Emory Angioplasty versus Surgery Trial J Am Coll Cardiol 2000;35:1116-1121.[Abstract/Free Full Text]
10. Henderson RA, Pocock SJ, Sharp SJ, et al. Long-term results of RITA-1 trial: clinical and cost comparisons of coronary angioplasty and coronary-artery bypass graftingRandomised Intervention Treatment of Angina. Lancet 1998;352:1419-1425.[Medline]
11. Hoffman SN, TenBrook JA, Wolf MP, Pauker SG, Salem DN, Wong JB. A meta-analysis of randomized controlled trials comparing coronary artery bypass graft with percutaneous transluminal coronary angioplasty: one- to eight-year outcomes J Am Coll Cardiol 2003;41:1293-1304.[Abstract/Free Full Text]
12. Serruys PW, Unger F, Sousa JE, et al. Arterial Revascularisation Therapies Study GroupComparison of coronary artery bypass surgery and stenting for the treatment of multivessel disease. N Engl J Med 2001;344:1117-1124.[Abstract/Free Full Text]
13. Rodriguez A, Bernardi V, Navia J, et al. ERACI II Investigators Argentine randomized studyCoronary angioplasty with stenting versus coronary bypass surgery in patients with multiple-vessel disease (ERACI II): 30-day and one-year follow-up results. J Am Coll Cardiol 2001;37:51-58.[Abstract/Free Full Text]
14. Blackstone EH. Comparing apples and oranges J Thorac Cardiovasc Surg 2002;123:8-15.[Free Full Text]
15. Rosenbaum PR, Rubin DR. The central role of the propensity score in observational studies for causal effects Biometrika 1983;70:41-55.[Abstract/Free Full Text]
16. Connors AF, Speroff T, Dawson NV, et al. The effectiveness of right heart catheterization in the initial care of critically ill patients JAMA 1996;276:889-897.[Abstract/Free Full Text]
17. Stenestrand U, Wallentin L. Early statin treatment following acute myocardial infarction and 1-year survival JAMA 2001;285:430-436.[Abstract/Free Full Text]
18. Jones RH, Kesler K, Phillips HR, et al. Long-term survival benefits of coronary artery bypass grafting and percutaneous transluminal angioplasty in patients with coronary artery disease J Thorac Cardiovasc Surg 1996;111:1013-1025.[Abstract/Free Full Text]
19. Fischman DL, Leon MB, Baim DS, et al. A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease N Engl J Med 1994;331:496-501.[Abstract/Free Full Text]
20. Serruys PW, de Jaegere P, Kiemeneij F, et al. A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease N Engl J Med 1994;331:489-495.[Abstract/Free Full Text]
21. Macaya C, Serruys PW, Ruygrok P, et al. Continued benefit of coronary stenting versus balloon angioplasty: one-year clinical follow-up of BENESTENT trial J Am Coll Cardiol 1996;27:255-261.[Abstract]
22. Van Domburg RT, Foley DP, Breeman A, et al. Coronary artery bypass graft surgery and percutaneous transluminal coronary angioplasty: 20 year clinical outcome Eur Heart J 2002;23:543-549.[Abstract/Free Full Text]
23. Morice MC, Serruys PW, Sousa JE, et al. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularisation N Engl J Med 2002;346:1773-1780.[Abstract/Free Full Text]
24. Moses JW, Leon MB, Popma JJ, et al. SIRIUS Investigators Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery N Engl J Med 2003;349:1315-1323.[Abstract/Free Full Text]

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Johanna J.M. Takkenberg Lex A. van Herwerden Patrick W.J.C. Serruys Ad J.J.C. Bogers Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by van Domburg, R. T. Articles by Bogers, A. J.J.C. Search for Related Content PubMed PubMed Citation Articles by van Domburg, R. T. Articles by Bogers, A. J.J.C. Related Collections Coronary disease