Eur J Cardiothorac Surg 2004;25:567-571
© 2004 Elsevier Science NL
Isolated high-grade lesion of the proximal LAD: a stent or off-pump LIMA?
Derk J. Drenth,
Nic J.G.M. Veeger,
Jan G. Grandjean,
Massimo A. Mariani,
Ad J. van Boven,
Piet W. Boonstra*
Thoraxcentre, Groningen University Hospital, Groningen, The Netherlands
Received 14 November 2003;
received in revised form 3 January 2004;
accepted 12 January 2004.
* Corresponding author. Address: Department of Cardiothoracic Surgery, University Hospital Groningen, P.O. Box 30001, 9700 RB Groningen, The Netherlands. Tel.: +31-50-361-32-38; fax: +31-50-3611-347
e-mail: p.w.boonstra{at}thorax.azg.nl
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Abstract
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Objectives: The objective of this study was to compare the long-term outcome of patients with an isolated high-grade stenosis of the left anterior descending (LAD) coronary artery randomized to percutaneous transluminal coronary angioplasty with stenting (PCI, stenting) or to off-pump coronary artery bypass grafting (surgery). Methods: Patients with an isolated high-grade stenosis (American College of Cardiology/American Heart Association classification type B2/C) of the proximal LAD were randomly assigned to stenting (n=51) or to surgery (n=51) and were followed for 3–5 years (mean 4 years). Primary composite endpoint was freedom from major adverse cardiac and cerebrovascular events (MACCEs), including cardiac death, myocardial infarction, stroke and repeat target vessel revascularization. Secondary endpoints were angina pectoris status and need for anti-anginal medication at follow-up. Analysis was by intention to treat. Results: MACCEs occurred in 27.5% after stenting and 9.8% after surgery (P=0.02; absolute risk reduction 17.7%). Freedom from angina pectoris was 67% after stenting and 85% after surgery (P=0.036). Need for anti-anginal medication was significantly lower after surgery compared to stenting (P=0.002). Conclusion: Patients with an isolated high-grade lesion of the proximal LAD have a significantly better 4-year clinical outcome after off-pump coronary bypass grafting than after PCI.
Key Words: Off-pump • Coronary artery bypass grafting • Beating heart surgery • Percutaneous coronary • Transluminal • Angioplasty
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1. Introduction
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Percutaneous transluminal coronary angioplasty with stenting (PCI) and off-pump coronary artery bypass grafting (surgery) are accepted treatments for symptomatic isolated stenosis of the proximal left anterior descending (LAD) coronary artery [1]. PCI to high-grade stenoses, according to the American College of Cardiology/American Heart Association classification type B2/C, of the LAD carries a high-risk for target vessel revascularization and morbidity [2,3]. Surgery may be a better alternative in such lesions [4].
In order to test this hypothesis we conducted a randomized study comparing both treatments for patients with an isolated high-grade type B2- or C-stenosis of the proximal LAD. We have previously reported that surgery and PCI do not differ in terms of periprocedural and short-term (6-months) major adverse cardiac and cerebrovascular events (MACCEs) [5]. A non-significant trend suggested that surgery may result in improved midterm clinical outcome [4,6].
We now report on the 4-year clinical follow-up of patients randomized to PCI or surgery for treatment of isolated high-grade proximal LAD lesions.
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2. Patients and methods
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Design and methods of this single-center randomized trial have been previously described [5]. In brief, patients with angina pectoris Canadian Cardiovascular Society (CCS) class 2 or more due to a high-grade type B2- or C-stenosis of the proximal LAD were studied [2]. All patients had to be eligible for both PCI and surgery by unanimous forum decision of cardiologists and cardiac surgeons. After written informed consent patients were included and randomly assigned to PCI or surgery. The study period was from 1997 to September 1999. The institutional ethics committee on human research approved the study. Cordis Europe financially supported this study in part, but did not take part in the conduct of the study.
2.1. Percutaneous coronary angioplasty with stenting
In the PCI-group, stent implantation was performed after predilatation. All patients received 250-mg ticlopidine daily from the day of stent implantation until 1 month after the procedure. Patients received 100-mg aspirin daily starting postprocedural day 1.
2.2. Off-pump coronary artery bypass grafting
Surgery was performed through a small left anterolateral thoracotomy on the beating heart, without cardiopulmonary bypass, using a mechanical coronary stabilizer (Guidant, USA) [7]. All patients received 100-mg aspirin daily starting postoperative day 1.
2.3. Endpoints
Primary endpoint of this study was the 4-year freedom from MACCEs. MACCEs were death, myocardial infarction, stroke and need for repeat target vessel revascularization (TVR). Secondary endpoints were angina pectoris class (according to the CCS) and need for anti-anginal medication at 4-year follow-up.
2.4. Follow-up and statistical analysis
Patients were all contacted by hospital and/or telephone and mailed questionnaires each at 6- and 12-month intervals after 3 years. Reported clinical events were confirmed by contacting treating physicians and adjudicated by an event monitoring committee of an experienced cardiologist and cardiac surgeon.
Baseline descriptive statistics for the continuous variables are the mean and standard error of the mean. For the normally distributed continuous variables, differences between the two treatments were evaluated by the Student's t-test. For skewed distributed continuous endpoints (P-value Shapiro–Wilk test for normality <0.05), the Mann–Whitney U test was used. For qualitative parameters (categorical or ordered), frequency counts and percentages of each category were calculated by treatment strategy. A Fisher's exact test or 
2 test was used to evaluate the differences between PCI and surgery.
The 4-year follow-up regarding the effect of PCI and surgery on the number of sustained MACCEs was evaluated with a survival analysis according to the intention to treat principle. Survival was estimated by the method of Kaplan–Meier. Using a log rank test the distribution of event-free survival between the two treatment strategies was compared. Risk ratios with 95% confidence intervals (95% CI) were estimated using the Cox proportional hazard model. All tests performed in order to test the (null-) hypothesis of no treatment difference were two-sided. A P-value <0.05 was considered statistically significant. For all analyses, commercially available computer software (Statistical Analysis System version 6.12, SAS Institute, Cary, NC) was used.
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3. Results
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Follow-up was complete for all patients (n=102). Mean follow-up time was 4 years (90% midrange 3.0–5.1 years). Patient characteristics at baseline did not differ between both treatment populations (Table 1). Early and midterm follow-up have been previously published [5,6].
At 4-year follow-up, MACCEs had occurred more frequently after PCI than after surgery, 90.2 versus 72.5%; P=0.02 (Fig. 1
; Table 2). The risk of MACCEs was reduced with a risk ratio of 0.3 with surgery compared to PCI (95% CI 0.1–0.9).
All cause mortality did not differ significantly between both treatment groups, although three patients died after surgery (Table 2). One patient died 3 days after surgery due to an ongoing inferoposterior myocardial infarction. Autopsy revealed a patent anastomosis but a 40% stenosis in the right coronary artery that was judged insignificant prior to the operation. Another patient died 1 week after discharge from hospital due to an unknown cause after an uncomplicated operation and convalescent period. The third patient died due to a pancreatic tumor 3.5 years after the initial operation. Until his death he had an uncomplicated postoperative course.
Although the patients under investigation had isolated LAD-disease at the start of the study, progression of their disease resulted in an additional non-TVR once in both treatment groups (Table 2). TVR was clinically driven and not angiographically driven.
More patients were free from angina 4 years after surgery 85 versus 67% (P=0.036; Table 3). The need for anti-anginal medication was also lower after surgery (P=0.002; Table 3).
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4. Discussion
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This study shows a significantly better outcome 4 years after off-pump surgery than after PCI in patients with an isolated high-grade stenosis of the proximal LAD. Surgery resulted in less major adverse events, less use of anti-anginal medication and a better angina pectoris status compared to PCI.
The first year is crucial for both the treatments (Fig. 1). Adverse events after surgery tend to occur during the first days, while the PCI-population is particularly at risk during the first year. The reported difference in MACCEs is mainly attributable to a difference in TVR and myocardial infarction after PCI. This finding confirms our hypothesis that clinical outcome after PCI is more dependent on the lesion type than outcome after surgery. In fact we found a 17.7% absolute risk reduction of MACCEs at 4-year follow-up when surgery was applied instead of PCI (P=0.02; risk ratio 0.3, 95% CI 0.1–0.9).
The clinical implication of our findings has to be placed in a broader perspective. Until now no randomized studies comparing off-pump surgery and PCI have reported a 4-year follow-up of patients with an isolated high-grade stenosis of the LAD. The SIMA (stenting vs. internal mammary artery)-trial, reported in their shorter 2.4 years follow-up, a better event-free survival (93 versus 69%, P<0.004) after conventional bypass surgery for the composite endpoint death, myocardial infarction and TVR [8]. This difference was mainly due to a higher restenosis rate in the stent-group (24 versus 0%). In contrast to our findings a difference in functional class and need for anti-anginal medication was not found [8]. In a similar study to our own, Diegeler et al. reported that off-pump surgery resulted in a superior major adverse cardiac event-free outcome than stenting at 1-year follow-up (15 versus 31%, P=0.02). This was primarily due to a higher TVR rate after stenting (29 versus 8%) [1]. Minimally invasive surgery resulted in an improved angina pectoris status at 6-month follow-up [1].
Although our study did not contain an on-pump surgery cohort, a comparison with on-pump surgery data could be made. We already reported a patency rate of 96% after surgery at 6-months angiographic follow-up [5]. So we do not doubt the quality of the off-pump anastomosis, and our patency rate can stand out with on-pump patency rates with a LIMA-LAD [9]. The 85% freedom from angina pectoris reported by us is comparable to previously reported freedom from angina pectoris in on-pump LIMA-LAD studies (71–90% at 5-year follow-up) for patients with isolated single vessel disease of the LAD [10–12]. In the prospective randomized MASS-trial, comparing medicine, angioplasty and on-pump surgery for single proximal LAD stenosis an additional coronary angiography was performed at 5-year follow-up [12]. At 5-year follow-up they reported a 73% freedom from angina after on-pump surgery [12]. In their angiography 50% of the patients who were free from apparent obstructive disease at baseline had developed >50% stenosis in vessels other than the LAD [12]. So probably progression of atherosclerosis plays a major role in the observed freedom from angina pectoris in patients treated for single vessel disease of the LAD. Compared with surgery, PCI is additionally hampered by restenosis. In our study two patients needed additional PCI for a non-LAD vessel.
Improvements in PCI, such as drug eluting stents (DES) and periprocedural use of gpIIb/IIIa receptor antagonists, were not available for standard use during our inclusion period. However, budgetary constraints currently allow only a limited use of DES and gpIIb/IIIa receptor antagonists in daily practice. The efficacy of both has not been tested in stent versus surgery trials [13,14]. The lesion types in which DES were initially studied, had a lower AHA-classification than the studied lesion in our population [13,14].
Recent data suggest that DES may not confer quite as large a reduction in restenosis rates as previously suggested when used in ‘the real world’ (i.e. in lesions with a higher risk profile). A recent registry of sirolimus eluting stent implantation in routine practice (including left main, bifurcation lesions, long lesions, small vessels, chronic total occlusions, in-stent restenosis and acute myocardial infarction) found restenosis in 19 out of 121 patients at 30 days [15]. Also, the observed restenosis rate after Cypher stent deployment was reported in up to 9% of all patients, 18% of all diabetic patients and 16% of patients with small-caliber vessels [16].
On the basis of our results we recommend surgery for patients with a high-grade lesion of the proximal LAD. Already after 4 years an absolute reduction of 17.7% for MACCEs is found compared to PCI. Additionally long-term patency in the surgery population can be expected. Although the introduction of gpIIb/IIIa receptor anatgonists and DES seems to result in a better short-term PCI outcome compared to bare metal stents, their long time superiority over bare metal stents and also surgery has to be proven in prospective randomized trials.
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5. Conclusion
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Patients with an isolated high-grade lesion of the proximal LAD have a significantly better 4-year clinical outcome after off-pump coronary bypass grafting than after PCI.
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Acknowledgments
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We acknowledge Cordis Europe, Waterloo, Belgium, for sponsoring this study in part and Trienke Steenhuis for data management.
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Abstract
1. Introduction
