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Ann Thorac Surg 2006;82:2067-2071
© 2006 The Society of Thoracic Surgeons

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Original Articles: Cardiovascular

Revascularization of Left Anterior Descending Artery With Drug-Eluting Stents: Comparison With Minimally Invasive Direct Coronary Artery Bypass Surgery

^a Department of Cardiothoracic Surgery, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv
^c Catheterization Laboratory, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv
^b Center for Quality, Safety and Data, Hadassah Hebrew University Hospital, Ein Karem, Jerusalem
^d Departments of Cardiology and Cardiac Surgery, Assuta Medical Center, Petach Tikva, Israel

Accepted for publication June 15, 2006.

^_* Address correspondence to Dr Mohr, Department of Cardiothoracic Surgery, Tel Aviv Sourasky Medical Center, 6 Weizman St, Tel Aviv 64239, Israel. (Email: marion{at}tasmc.health.gov.il).

Adult cardiac surgery: The Annals of Thoracic Surgery CME Program is located online at http://cme.ctsnetjournals.org. To take the CME activity related to this article, you must have either an STS member or an individual non-member subscription to the journal.

 

	Abstract

Top Abstract Introduction Patients and Methods Results Comment References

 
BACKGROUND: The proximal left anterior descending artery (LAD) is a challenging area for percutaneous interventions; therefore, coronary artery bypass grafting is often considered and sometimes performed even in patients with single-vessel disease involving the proximal LAD. This study compares mid-term results of LAD revascularization using drug-eluting stents (Cypher) with minimally invasive direct coronary artery bypass grafting (MIDCAB).

METHODS: From May 2002 to December 2003, 376 consecutive patients underwent myocardial revascularization of the LAD, 272 by Cypher and 104 by MIDCAB. After matching for age, sex, and extent of coronary artery disease, two groups of 83 patients each were used to compare the two revascularization modalities. The groups were similar; however, ejection fraction of less than 0.35 was more prevalent in the MIDCAB group and prior percutaneous coronary intervention in the Cypher group.

RESULTS: Thirty-day mortality was 1.1% in the MIDCAB and 0% in the Cypher group. Mean follow-up was 22.5 months. Two late cardiac deaths occurred in the MIDCAB group and one in the Cypher group (p = NS). Angina returned in 35% of the Cypher group and in 8.4% of the MIDCAB group (p < 0.001). There were 14 (16.8%) reinterventions in the Cypher compared with three (3.6%) in the surgical group (p = 0.005). Cox proportional hazard model showed that assignment to the Cypher group was the only independent predictor of reangina (hazard ratio [HR], 6.17, 95% confidence interval [CI], 2.46 to 15.4). Treatment with Cypher was also an independent predictor of reintervention (HR 8.26, 95% CI, 1.68 to 40).

CONCLUSIONS: Despite improved results of percutaneous interventions with Cypher to the LAD, mid-term clinical outcome of patients treated with MIDCAB was better.

In patients with multivessel disease, surgical revascularization of the left anterior descending (LAD) with the internal thoracic artery (ITA) is still the only proven method of improving event-free survival [1, 2]. The proximal LAD is a challenging area for percutaneous interventions (PCI) because of concern for injury to the left main artery or occlusion of major side branches [3]. Therefore, coronary artery bypass grafting (CABG) is often considered, and sometimes performed, even in patients with single-vessel disease.

Considerable reduction of restenosis and reintervention rates was recently reported with the introduction of drug-eluting stents [4, 5]. In a recent report of 459 patients with single LAD stenosis, drug-eluting stents significantly decreased restenosis and reintervention rates compared with bare-metal stents [6].

Most patients with single-vessel disease involving the proximal LAD referred for bypass surgery in our institution are operated on using the minimally invasive direct coronary artery bypass (MIDCAB) technique. We therefore decided to compare their outcome with that of matched patients who underwent PCI with drug-eluting stents.

	Patients and Methods

Top Abstract Introduction Patients and Methods Results Comment References

 
Between June 2002 and December 2003, 104 patients underwent MIDCAB with left ITA to the LAD, and 272 underwent PCI with LAD revascularization by means of sirolimus drug-eluting stents (Cypher, Cordis, Johnson & Johnson, Miami Lakes, FL). The preoperative characteristics of MIDCAB and Cypher patients were not similar. Cypher patients were younger and had an increased prevalence of multivessel disease (35% versus 16%). To control for these differences between MIDCAB and Cypher patients, we compared results between the two treatment modalities only after matching for age, sex, and the extent of coronary artery disease (Table 1). Each of the two matched groups thus created contained 83 patients. Baseline characteristics of patients in both groups are summarized in Table 2.

During the study period, selection criteria for surgery versus PCI were mainly technical. In principle, there was a preference to refer patients for surgery for the following reasons:

• Comorbid diseases such as diabetes mellitus and renal failure.

• In-stent restenosis or thrombosis of a coronary artery.

• Complex type C lesions (calcified coronary arteries, lesion length exceeding 20 mm, twisted arteries, suspicion of a thrombus in an artery), or bifurcation lesion involving a major diagonal branch.

• Cypher drug-eluting stents were not available.

• Complete occlusion.

• Patient’s or cardiologist’s preference.

All MIDCAB patients were operated on without extracorporeal circulation, and all surgical procedures included implantation of a single graft (left ITA) to the LAD. The MIDCAB technique was described in detail by Diegeler and colleagues [7]. In brief, a limited left anterolateral thoracotomy was performed through the fourth intercostal space. The internal thoracic artery was harvested under direct vision. After administration of heparin (200 U/kg), the activated clotting time was kept on an elevated level of more than 400 seconds by repeat application of heparin, if needed.

The internal thoracic artery was divided distally. Local immobilization of the anastomotic site was achieved with mechanical stabilizers. The anastomosis was performed with the use of one running 7-0 polypropylene suture on the beating heart. Protamine was applied to partially neutralize the dose of heparin. Wounds were closed in a standard fashion.

In the PCI group, stent implantation was performed after balloon angioplasty dilatation. All patients received aspirin (325 mg daily) before and after the procedure and a 300-mg loading dose of clopidogrel the day before the procedure and 75 mg daily for at least 3 months thereafter. During the procedure all patients were treated intravenously with heparin. In most patients, only one Cypher stent was used for the LAD; however, more than one was used if required (eg, long lesion, dissection). In 2 patients with bifurcation lesion, PCI included treatment of two vessels (LAD and diagonal branch) (Table 1).

Acute myocardial infarction (within the previous 48 hours), poor ejection fraction (0.25), left main disease, calcification, or thrombus within the LAD, long lesions (>30 mm) and bifurcation lesions were major criteria for exclusion of patients from the group treated with stents to the LAD. Patients with diabetes mellitus or ostial LAD lesions were not excluded. All patients in the MIDCAB group were treated postoperatively with an intravenous infusion of isosorbide dinitrate (Isoket 4–20 mg/h) during the first postoperative 24–48 hours [8].

Statistical Analysis
Data are expressed as mean ± SD or proportions, as appropriate. The two groups were matched for age, sex, and extent of coronary artery disease. The ² test and Fisher exact test were used in the stepwise method to compare discrete variables. The Cox proportional hazard model was used to evaluate risk factors for early return of angina and reintervention. Hazard ratio (HR) and 95% confidence interval (CI) were given. Survival Postoperative survival free of angina, major adverse cardiovascular event (MACE), and reintervention are expressed by the Kaplan-Meier method, and comparison between groups was made by the log-rank test. All analyses were performed by SPSS 12 software (SPSS Inc, Chicago, IL).

	Results

Top Abstract Introduction Patients and Methods Results Comment References

 
After matching for age, sex, and extent of coronary artery disease (Table 1), the two groups were similar. However, poor ejection fraction (<0.30) was more prevalent in the MIDCAB group, and prior PCI to the LAD was more common among the Cypher group (Table 2). Two-vessel or three-vessel disease was present in 48% of the patients in both groups. In the PCI group, the relatively high number of untreated vessels reflects a policy of treating the culprit lesions, especially in patients with significant LAD stenosis, without objective evidence for ischemia in the other coronary beds. In the surgical group, the decision to address only the culprit LAD lesion and thus perform a minimally invasive procedure with its associated incomplete revascularization [9] was made preoperatively by the surgeon together with the patient and the referring cardiologist.

Reasons for performing the MIDCAB procedure included age older than 80 years (n = 8), chronic renal failure (n = 3), malignancy (n = 3), advanced peripheral vascular disease (n = 3), morbid obesity (n = 3), chronic obstructive pulmonary disease (n = 2), and neurologic incapacity after stroke (n = 2). The desire by cardiologists and patients to minimize surgical trauma was the only indication for referral to MIDCAB in the remaining patients with two-vessel or three-vessel disease.

Thirty-day mortality was 1.1% in the MIDCAB group and 0% in the Cypher group. Mean follow-up was 22.5 months (range, 6 to 33 months). One late death occurred in the Cypher group and four in the MIDCAB group (p = 0.173); however, only two of the four deaths were cardiac-related. The 2-year actuarial survival (Kaplan-Meier) was not different statistically (98% versus 93% in the Cypher versus MIDCAB group, p = 0.11). Angina returned in 29 patients (35%) of the Cypher group compared with 7 (8.4%) in the MIDCAB group (p < 0.001). There were 14 reinterventions (16.8%) in the Cypher group: 11 coronary angioplasties and three surgical interventions. There were three (3.6%) reinterventions (all PCI) in the surgical group (p = 0.005, Cypher versus MIDCAB). Seven patients in the Cypher group underwent reintervention to the LAD, compared with only 1 in the MIDCAB group (p = 0.029). Three patients of the Cypher and 1 of the MIDCAB group had more than one reintervention during the follow-up period.

The prevalence of reinterventions was higher in the PCI group and in the surgical group among patients with multivessel disease (20% and 5%, respectively) compared with 7% and 0%, respectively, in patients with single-vessel disease; however, the difference did not reach statistical significance (p = 0.109 and p = 0.229, respectively).

During the follow-up period, there were two myocardial infarctions in the MIDCAB group and five in the Cypher group (p = NS). The occurrence of MACE, consisting of cardiac mortality, myocardial infarction, or reintervention, was significantly higher in the Cypher group at 20.5% (17 events) versus 7.2% (6 events) in the surgical group (p = 0.013). Independent predictors of MACE (Cox analysis) were assignment to the Cypher group (HR, 4.1; 95% CI, 1.26 to 13.16), multivessel disease (HR, 4.3; 95% CI, 1.44 to 13.16), and prior PCI (HR, 4.36; 95% CI, 1.28 to 14.90).

Two-year angina-free survival (Kaplan-Meier) of the MIDCAB patients was 87.4% compared with 57% in the PCI patients (p = 0.002, long-rank test) (Fig 1). The difference in 2-year reintervention-free survival did not reach statistical significance (91.6% versus 81.7%, p = 0.118 log-rank test). However, the difference in MACE-free survival was significant (94.7% versus 79%, p = 0.007) (Fig 2).

View larger version (14K): [in this window] [in a new window]   Fig 1. Angina-free survival of Cypher versus minimally invasive direct coronary artery bypass (MIDCAB) groups by Kaplan-Meier analysis.

View larger version (13K): [in this window] [in a new window]   Fig 2. Major adverse cardiac event (MACE)-free survival of patients undergoing Cypher to the left anterior descending artery versus minimally invasive direct coronary artery bypass (MIDCAB) by Kaplan-Meier analysis.

	Comment

Top Abstract Introduction Patients and Methods Results Comment References

 
Most symptomatic patients with isolated stenosis of the LAD are treated today percutaneously with stents [10]. The risk of late morbidity and reintervention when the proximal segment of the LAD is involved [11, 12] was recently decreased with the introduction of drug-eluting stents [6]. The MIDCAB technique enables surgical revascularization of the LAD through a small left anterior thoracotomy [13]. The reported patency rate of the anastomosis from the left internal mammary artery to the LAD is more than 90% and is not significantly different than that reported for surgical revascularization incorporating midsternotomy [14–17]. This procedure has a relatively low rate of complications and restenosis. It reduces surgical trauma and gives a satisfactory cosmetic effect [17–20].

Several recently published reports comparing MIDCAB with stents have documented superior clinical and angiographic outcome of surgical treatment over stenting in LAD revascularization [17, 20, 21]. However, MIDCAB in these reports was compared with PCI of the LAD with bare-metal stents. In our study, all PCI patients were treated with Cypher drug-eluting stents.

To control for differences between groups in preoperative characteristics, treatment groups were compared only after matching for age, sex and extent of coronary artery disease, and the Cox proportional hazard model was used to define independent predictors of adverse outcome events like reangina, reintervention, and MACE. After a mean follow-up of almost 2 years, which is long enough for the development of in-stent restenosis [22], survival was similar; however, less than 60% of the Cypher patients were angina-free, and 11 (13.2%) required one or two reinterventions. Target vessel (LAD) reintervention in the Cypher-treated group was 8.4% (7 patients) compared with 1.2% (1 patient) in the MIDCAB group. After a mean follow-up period of almost 2 years, only 79% of the Cypher group was free of MACE compared with 94% of the MIDCAB group.

Despite the relatively high incidence of incomplete revascularization in both groups, the only independent predictor for angina recurrence and reintervention in our study was assignment to the Cypher group. Assignment to the Cypher group was not the only predictor of MACE, however. Other predictors were incomplete revascularization and prior PCI.

Important covariates (mainly technical), such as vessel diameter or lesion length, were not included in the analysis. These variables, which are less important in the surgical group, may affect restenosis, reangina, and reintervention in the PCI group. Owing to the exclusion criteria for drug-eluting stents, only type A and type B lesions were addressed by PCI in this study. If one would focus on the entire patient population with all types of LAD lesions, the results might have been more definitive in favor of the surgical group. Larger prospective multicenter studies are required to determine the effect of lesion morphology in patients selected for PCI or surgery in this evolving era of drug-eluting stents.

Another limitation of this study is the relatively limited mean follow-up period of 22 months. Evidence is growing that drug-eluting stents may develop delayed thrombosis related to delayed endothelialization, hypersensitivity to the stent polymer, or discontinuation of antiplatelet treatment [23, 24]. Longer follow-up is therefore required.

In conclusion, mid-term clinical outcome of MIDCAB patients was better than that of patients treated with percutaneous intervention with a Cypher drug-eluting stent to the LAD. The reangina and reintervention gap [24] between surgery and percutaneous interventions may further be reduced by better patient selection and avoiding lone PCI to the LAD in patients with multi-vessel disease or patients with prior PCI to this vessel.

	References

Top Abstract Introduction Patients and Methods Results Comment References

 

1. Barner HB, Swartz MI, Mudd JG, Tyras DH. Late patency of the internal mammary artery as a coronary artery bypass conduit Ann Thorac Surg 1982;34:408-412.[Abstract]
2. Loop FD, Lytle BW, Cosgrove DM, et al. Influence of internal-mammary-artery-graft on 10 year survival and other cardiac events N Engl J Med 1986;314:1-6.[Abstract]
3. Kimura BJ, Russo RJ, Bhargava V, McDaniel MB, Peterson KL, Demaria AN. Atheroma morphology and distribution in proximal left anterior descending coronary artery: in vivo observations J Am Coll Cardiol 1996;27:825-831.[Abstract]
4. Morice MC, Serruys PW, Sousa E, et al. RAVEL Study Group Randomized Study with the Sirolimus-Coated Bx Velocity Balloon-Expandable Stent in the Treatment of Patients with de Novo Native Coronary Artery LesionsA randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med 2003;346:1173-1180.
5. Sousa JE, Costa MA, Abizaid A, et al. Lack of neointimal proliferation after implantation of sirolimus-coated stents in human coronary arteries: a quantitative coronary angiography and three-dimensional intravascular ultrasound study Circulation 2001;103:192-195.[Abstract/Free Full Text]
6. Sawhney N, Moses JW, Leon MB, et al. Treatment of left anterior descending coronary artery disease with sirolimus-eluting stents Circulation 2004;110:374-379.[Abstract/Free Full Text]
7. Diegeler A, Falk V, Matin M, et al. Minimally invasive coronary artery bypass grafting without cardiopulmonary bypass: early experience and follow-up Ann Thorac Surg 1998;66:1022-1025.[Abstract/Free Full Text]
8. Gurevitch J, Miller HI, Shapira I, et al. High-dose isosorbide dinitrate for myocardial revascularization with composite arterial grafts Ann Thorac Surg 1997;63:382-387.[Abstract/Free Full Text]
9. Bell MR, Gersh BJ, Schaff HV, et al. Effect of completeness of revascularization on long-term outcome of patients with threee-vessel disease undergoing coronary artery bypass surgeryA report from the Coronary Artery Surgery Study (CASS) registry. Circulation 1992;86:446-457.[Abstract/Free Full Text]
10. Versaci F, Gaspardone A, Tomai F, Crea F, Chiariello L, Gioffre PA. A comparison of coronary artery stenting with angioplasty for isolated stenosis of the proximal left anterior descending coronary artery N Engl J Med 1997;336:817-822.[Abstract/Free Full Text]
11. Ryan TJ, Bauman WB, Kennedy JW, et al. Guidelines for percutaneous transluminal coronary angioplastyA report of the American Heart Association/American College of Cardiology Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Committee on Percutaneous Transluminal Coronary Angioplasty). Circulation 1993;88:2987-3007.[Free Full Text]
12. Eagle KA, Guyton RA, Davidoff R, et al. ACC/AHA guidelines for coronary artery bypass graft surgery: executive summary and recommendations: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (committee to revise the 1991 guidelines for coronary artery bypass graft surgery) Circulation 1999;100:1464-1480.[Free Full Text]
13. Calafiore A, DiGiammarco G, Teodori G, et al. Left anterior descending coronary artery grafting via left anterior small thoracotomy without cardiopulmonary bypass Ann Thorac Surg 1996;61:1658-1665.[Abstract/Free Full Text]
14. Mack MJ, Magovern JA, Acuff TA, et al. Results of graft patency by immediate angiography in minimally invasive coronary artery surgery Ann Thorac Surg 1999;68:383-389.[Abstract/Free Full Text]
15. Mariani MA, Boonstra PW, Grandjean JG, et al. Minimally invasive coronary artery bypass grafting versus coronary angioplasty for isolated type C stenosis of the left anterior descending artery J Thorac Cardiovasc Surg 1997;114:434-439.[Abstract/Free Full Text]
16. Oliveira SA, Lisboa LAF, Dallan LAO, Rojas SO, de Figueiredo LFP. Minimally invasive single-vessel coronary artery bypass with the internal thoracic artery and early postoperative angiography: midterm results of a prospective study in 120 consecutive patients Ann Thorac Surg 2002;73:505-510.[Abstract/Free Full Text]
17. Diegler A, Matin M, Kayser S, et al. Angiographic results after minimally invasive direct coronary artery bypass grafting (MIDCAB) approach Eur J Cardiothoracic Surg 1999;15:680-684.[Abstract/Free Full Text]
18. Cisowski M, Drzewiecki J, Drzewiecka-Gerber A, et al. Primary stenting versus MIDCAB: preliminary report-comparison of two methods of revascularization in single left anterior descending coronary artery stenosis Ann Thorac Surg 2002;74:S1334-S1339.[Abstract/Free Full Text]
19. Diegeler A, Spyrantis N, Matin M, et al. The revival of surgical treatment for isolated proximal high grade LAD lesions by minimally invasive coronary artery bypass grafting Eur J Cardiothorac Surg 2000;17:501-504.[Abstract/Free Full Text]
20. Diegeler A, Thiele H, Falk V, et al. Comparison of stenting with minimally invasive bypass surgery for stenosis of the left anterior descending coronary artery N Engl J Med 2002;347:561-566.[Abstract/Free Full Text]
21. Drenth DJ, Veeger NJGM, Grandjean JG, Mariani MA, van Boven AJ, Boonstra PW. Isolated high-grade lesion of the proximal LAD: a stent or off-pump LIMA? Eur J Cardiothorac Surg 2004;25:567-571.[Abstract/Free Full Text]
22. Kimura T, Nosaka H, Yokoi H, Iwabuchi M, Nobuyoshi M. Serial angiographic follow-up after Palmaz-Schatz stent implantation: comparison with conventional balloon angioplasty J Am Coll Cardiol 1993;21:1557-1563.[Abstract]
23. Vimani R, Farb A, Guagliumi G, Kolodgie FD. Drug-eluting stents: caution and concerns for long-term outcome Coron Artery Dis 2004;15:313-318.[Medline]
24. SOS Investigators Coronary artery bypass surgery versus percutaneous coronary intervention (PCI) with stent implantation in patients with multivessel coronary artery disease (the Stent or Surgery trial): a randomized, controlled trial Lancet 2002;360:961-962.[Medline]

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