Original Article
Treatment of left anterior descending coronary artery stenosis: stent or surgery
Asian Cardiovascular & Thoracic Annals 21(5) 528–532 ß The Author(s) 2012 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0218492312461262 aan.sagepub.com
Mesut Sismanoglu, Sabit Sarıkaya, Oruc Alper Onk, Taylan Adademir, Eray Aksoy and Kaan Kırali
Abstract Background: Drug-eluting stents have emerged as a solution to the problem of restenosis after bare-metal stent implantation, as an alternative to off-pump coronary bypass, for isolated left anterior descending coronary artery lesions at short-term follow-up. However, long-term follow-up is yet to be defined. Methods: From January to December 2004, 64 consecutive patients underwent myocardial revascularization: 31 by drug-eluting stents and 33 by off-pump coronary bypass. The primary endpoint was angiographic outcome, and the secondary endpoint was clinical outcome at 5 years. Results: There was no early or late mortality in either group. Hospital stay was significantly shorter in the stent group (2.5 2.1 vs. 7.1 4.9 days, p ¼ 0.003). Long-term patency was higher and major adverse cardiac events (recurrence of angina and revascularization of target vessel) were encountered less frequently in the coronary bypass group, although not significantly. Conclusion: The 5-year follow-up showed no significant difference between the off-pump coronary bypass and stent groups for the primary and secondary endpoints. As a significant difference between treatment options is lacking, decision-making for appropriate treatment in this group of patients requires the collaboration of cardiologists and cardiovascular surgeons and an individual approach, to achieve successful long-term outcomes.
Keywords Coronary artery bypass, off-pump, coronary artery disease, drug-eluting stents, heart catheterization, treatment outcome
Introduction
Patients and methods
Percutaneous intervention and off-pump coronary artery bypass (OPCAB) are both well-accepted treatment options for isolated high-grade stenosis of the proximal left anterior descending (LAD) coronary artery. Randomized trials comparing bare metal stenting with OPCAB surgery have shown a significantly higher reintervention rate for stenting and similar results for mortality and reinfarction.1 Drug-eluting stents (DES) have emerged as a solution to the problem of restenosis after bare-metal stent implantation, but there are only a few reports comparing early results of DES and OPCAB for isolated LAD stenosis.2,3 We report the 5-year results of a trial comparing surgical revascularization with the left internal mammary artery (LIMA) and intracoronary DES in patients with proximal LAD stenosis.
This prospective non-randomized study was approved by the local ethics committee. Patients with chronic stable angina pectoris caused by an isolated proximal LAD lesion (>70% stenosis, no total occlusion) were selected from January 2004 to December 2004 in Kartal Kosuyolu Heart and Research Hospital. Patients who were eligible for both OPCAB and percutaneous angioplasty with primary stenting were asked to choose one
Department of Cardiovascular Surgery, Kosuyolu Heart and Research Hospital, Istanbul, Turkey Corresponding author: Kaan Kırali, MD, Kartal Kos¸uyolu Yu¨ksek Ihtisas Eg˘itim ve Aras¸tırma Hastanesi, Kartal, Istanbul 34846, Turkey. Email: [email protected]
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of the treatment protocols. After written informed consent was obtained, the patients were assigned to stenting or surgery. Exclusion criteria were acute coronary syndromes, additional significant coronary lesions, valvular heart disease, gastrointestinal intolerance to anticoagulant treatment, and previous interventional or surgical treatment for coronary artery disease. There were 64 patients who met the inclusion criteria; 31 of them wanted to have stent placement and 33 chose to undergo OPCAB. The baseline demographic and angiographic characteristics of patients were similar, but those in the OPCAB group were significantly younger and had less family history of coronary artery disease (Table 1). OPCAB was performed through a median sternotomy without cardiopulmonary bypass. The LIMA was harvested and the LIMA-LAD anastomosis was carried out during heparinization (activated clotting time >300 s) on a beating heart, using a running 7/0 Prolene suture, with the help of a mechanical coronary stabilizer (Genzyme Immobilizer System; Teleflex Medical, Research Triangle Park, NC, USA) and temporary occlusion of the LAD with a proximal snare. Heparin was neutralized with a 2/1 ratio of protamine at the end of the procedure. All patients received 150 mg of aspirin daily, starting on postoperative day 1. For stent implantation, a coronary guiding catheter of 6 F to 8 F was used to access the coronary arteries through the femoral approach. After predilatation, the optimal DES was implanted at the target site, covering the entire lesion. A narrowing of 0% by visual estimation or 20% by quantitative coronary angiography with TIMI grade 3 distal flow was the goal. All patients were pretreated with 300 mg of aspirin and 600 mg of clopidogrel 24 h before angioplasty with stenting. A bolus of 10,000 IU of heparin was administered intravenously after sheath insertion (activated clotting time >300 s).
No protamine was given at the end of the procedure. All patients received 100 mg of aspirin and 75 mg of clopidogrel daily from stent implantation until 1 year after the procedure. In both groups, patients had electrocardiographic monitoring during the first 24 h after the procedure, and creatine kinase and creatine kinase-MB levels were estimated during the first 3 days. A 12-lead electrocardiogram was obtained daily or when clinically required. All patients were followed up for 5 years until their preplanned coronary angiography. The primary endpoint of the study was the 5-year angiographic follow-up. Secondary endpoints were major adverse cardiac and cerebrovascular events (MACCE), status of angina pectoris, use of medication, need for repeat target vessel revascularization, and hospitalization time. Five years after the initial procedure, quantitative coronary angiography was performed. From 2 orthogonal views, the percentage of the diameter of stenosis was calculated as a mean. Successful revascularization in the OPCAB group was defined as a percentage stenosis diameter of the anastomosis of less than 50% of the mid-LITA diameter, and in the stent group, as the percentage of the diameter of stenosis in the stented segment of less than 50% of the reference diameter of the LAD. The quality of the revascularization of the target vessel was graded as: no abnormalities or small irregularities; nonsignificant stenosis (20%–50% luminal stenosis); or stenotic (>50% luminal stenosis).4 This study was powered to evaluate the 5-year eventfree survival of the ongoing study. For evaluation of the angiographic outcome in this study, an analysis was planned for the first 64 patients. For this analysis, no formal sample size calculation was performed. Statistical analysis was undertaken in accordance with the intention-to-treat principle. In this setting, patients
Table 1. Baseline characteristics of 64 patients undergoing OPCAB or stenting. Variable
Stenting (n ¼ 31)
OPCAB (n ¼ 33)
p value
Age (years) Family history of CAD Sex (male/female) Smoking History of MI Diabetes mellitus Hypertension Hypercholesterolemia Chronic renal failure LV dysfunction
57.2 11.7 18 (56.3%) 22/10 11 (34.4%) 14 (43.8%) 6 (18.8%) 17 (53.1%) 11 (34.4%) 2 (6.1%) 11 (34.4%)
50.5 11.5 8 (23.5%) 20/13 14 (41.2%) 20 (58.8%) 12(35.3%) 22 (64.7%) 11 (32.4%) 3 (8.8%) 12 (32.4%)
0.03 0.01 0.58 0.62 0.62 0.17 0.45 0.86 1 0.86
CAD: coronary artery disease; LV: left ventricular; MI: myocardial infarction; OPCAB: off-pump coronary artery bypass.
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were evaluated on the basis of the treatment they chose. The baseline descriptive statistics for continuous variables are given as the mean and standard error. For normally distributed continuous variables, the differences between the 2 strategies were evaluated with Student’s t test. For continuous endpoints with a skewed distribution, 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. Fisher’s exact test or the chi-squared test was used to evaluate the differences between surgical intervention and stenting. The quantitative coronary angiography outcomes of both treatments at the 5-year follow-up were evaluated with the chi-squared test. For all analyses, commercially available computer software (Statistical Package for Social Sciences, release 16.0; SPSS, Inc., Chicago, IL, USA) was used.
Results No patient in the stent group crossed over to OPCAB and vice versa. There was no early mortality in either group. OPCAB was performed as planned in all patients, and the operations were uneventful. Bleeding that required reintervention occurred in 1 (3.0%) patient and blood transfusion was necessary in 7 (21.2%). The mean length of hospital stay was 7.1 4.9 days (range, 4–26 days). In the stent group, the mean length of hospital stay was 2.5 2.1 days (range, 1–9 days; p ¼ 0.003). One (3.2%) patient had a myocardial infarction after stenting as a result of occlusion of a diagonal branch, and groin bleeding requiring blood transfusion occurred in 2 (6.5%). The mean follow-up was 5.2 0.9 years. There was no mortality at the end of 5 years in either group. Follow-up quantitative angiography was performed in all patients. In 93.9% (31/33 patients) of OPCAB patients, patency of the LIMA graft was noted, and 5 (16.1%) in the stent group had restenosis defined as 50% or more stenosis (p ¼ 0.19; Table 2). In the OPCAB group, one patient was treated by conventional angioplasty by placement of a stent within the LIMA, and another underwent coronary artery bypass grafting. In the stent group, 3 patients were treated by conventional angioplasty (placement of a second stent within the first one) and 2 underwent coronary artery bypass grafting. The Canadian Cardiovascular Society angina class of the treatment groups revealed no differences at the end of the 5-year follow-up (Table 3): 28 (84.8%) patients in the OPCAB group and 22 (71%) in the stent group were in class 0 or 2 (p > 0.05). Only 5 patients in the OPCAB group were in class II or III compared with 9 in the stent group (p > 0.05). At the end of the 5-year follow-up, antianginal drugs were
prescribed to 15% of the patients treated by OPCAB and to 30% of those treated by stent implantation (p > 0.05). The quality of revascularization of the target vessel at the end of 5 years seemed better in the OPCAB group (Table 4), but the difference was not statistically significant.
Discussion We found that both revascularization strategies were safe and effective up to the 5-year follow-up. Although the differences were not significant, trends favoring surgery were observed in clinical improvement and quality of revascularization. Bare-metal stent revascularization of proximal LAD lesions has a 29%–44% restenosis rate.5,6 DES emerged as a solution to this problem, as an alternative to OPCAB which has more than 90% LIMA-LAD longterm patency.7,8 Both restenosis and reintervention rates have reduced significantly with the use of DES. Although higher restenosis rates were reported in diabetic patients with small and complex lesions (that might also impair results of surgery), restenosis rates
Table 2. Adverse events during follow-up. Event
Stenting (n ¼ 31)
OPCAB (n ¼ 33)
Death Nonfatal myocardial infarction Cerebrovascular accident Recurrent AP Repeat revascularization Hospitalization for unstable AP MACCE
0 3 (9.7%) 0 14 (45.2%) 5 (16.1%) 3 (9.7%) 7 (22.5%)
0 3 0 8 2 3 4
p value
(9.1%)
0.66
(24.5%) (6.1%) (9.1%) (12.2%)
0.06 0.19 0.66 0.23
AP: angina pectoris; MACCE: major adverse cardiac and cerebrovascular events; OPCAB: off-pump coronary artery bypass.
Table 3. Canadian Cardiovascular Society angina class at 5 years. CCS class
Stenting (n ¼ 31)
OPCAB (n ¼ 33)
0 1 2 3 4
17 (54.8%) 5 (16.1%) 6 (19.4%) 3 (9.7%) 0
25 (75.7%) 3 (9.1%) 2 (6.1%) 3 (9.1%) 0
p value >0.05 >0.05 >0.05 >0.05
CCS: Canadian Cardiovascular Society; OPCAB: off-pump coronary artery bypass.
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Table 4. Quality of revascularization of the target vessel at 5 years. Quality
Stenting (n ¼ 31)
OPCAB (n ¼ 33)
p value
No abnormalities Nonsignificant stenosis (20%–50%) Stenosis (>50%)
17 (54,8%) 9 (29.1%) 5 (16.1%)
25 (75.7%) 6 (18.2%) 2 (6.1%)
>0.05 >0.05 >0.05
OPCAB: off-pump coronary artery bypass.
are no more than 10% in the short term.9–13 There are limited data comparing DES and OPCAB in the long term. In our study, OPCAB had a slightly better angiographic outcome than DES at the 5-year follow-up. Five-year follow-up coronary angiography reveled 83.9% patency after DES and 93.9% after OPCAB (p ¼ 0.19). There was no early or late mortality in either group. Mean hospitalization time after OPCAB was 7.1 4.9 days, and that after stenting was 2.5 2.1 days. This shorter convalescence period reflects the true minimally invasive character of stenting, as shown in other studies.14 Periprocedural complications, MACCE, angina class, or use of antianginal medication did not differ significantly between groups. Studies comparing DES and OPCAB for recurrence of angina favor surgery with increasing follow-up time.3,15–19 At 5 years, 54.8% of patients with DES and 75.5% of those with OPCAB had angina-free survival. Hong and colleagues3 revealed 1.7% repeat target vessel revascularization after DES and 5.9% after surgery at 6 months of follow-up. Other studies with longer follow-up time have favored surgery.15,17 Etienne and colleagues18 noted revascularization rates of 13.6% and 2.6% for DES and surgery, respectively, after 2 years. In our study, 14 (45.2%) of the patients with DES had some degree of restenosis whereas 8 (24.3%) cases of restenosis were seen after surgery. Although repeat target vessel revascularization did not differ significantly at 5 years, a difference can be expected after longer follow-up. A recent meta-analysis by Jaffery and colleagues19 showed similar periprocedural myocardial infarction rates for stenting and surgery. Three patients in each group suffered myocardial infarction in our study. MACCE rates also favored surgery in our study (22.5% vs. 12.2%). A study comparing sirolimus-eluting stenting vs. minimally invasive direct coronary bypass grafting surgery revealed 7.7% MACCE rates for both groups at 12 months, most probably due to a high rate of myocardial infarction after surgery.20 Other studies have favored surgery on the basis of MACCE rates.3,15,17–19 Ben-Gal and colleagues2 showed MACCE rates of 21% for DES and 6% for surgery at 2 years. Treatment of isolated high-grade stenosis of the LAD with DES is less invasive, requires a shorter hospital stay, and is usually associated with less acute morbidity compared to standard coronary artery
bypass surgery. OPCAB surgery is an acceptable alternative to standard coronary artery bypass grafting. The quality of coronary anastomoses is the main concern in OPCAB surgery, due to the need to perform anastomoses on a beating heart with a temporarily occluded coronary artery. Studies have demonstrated that OPCAB appears to give similar anastomotic patency to conventional coronary artery bypass grafting. The major advantage of OPCAB is avoidance of cardiopulmonary bypass. Despite the advantages, OPCAB is technically demanding and still more invasive than stenting, with a longer mean hospital stay (7.1 vs. 2.5 days in this study). Although the difference was not significant, there were more patients with restenosis and repeat revascularization in the DES group at 5 years. Use of glycoprotein 2b/3a inhibitors might decrease the restenosis rate in these patients. In our study, there was still a trend in favor of surgery, which at longer follow-up might be further attenuated. The rates of complete angina relief, restenosis, and MACCE were better with OPCAB surgery. In conclusion, patients with isolated LAD coronary artery stenosis can be treated safely with OPCAB or DES placement. DES remains hampered by the risk of restenosis and need for repeated revascularization. Stenting may be more suitable for some lesions with a low to intermediate restenosis risk, whereas surgery may provide excellent outcomes regardless of lesion morphology, including chronic total occlusion. Therefore, each lesion requires an interdisciplinary approach for selection of the best treatment option. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Conflicts of interest statement None declared.
References 1. Thiele H, Oettel S, Jacobs S, Hambrecht R, Sick P, Gummert JF, et al. Comparison of bare-metal stenting with minimally invasive bypass surgery for stenosis of the left anterior descending coronary artery. A 5-year follow-up. Circulation 2005; 112: 3445–3450.
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2. Ben-Gal Y, Mohr R, Braunstein R, Finkelstein A, Hansson N, Hendler A, et al. Revascularization of left anterior descending artery with drug-eluting stents: comparison with minimally invasive direct coronary artery bypass surgery. Ann Thorac Surg 2006; 82: 2067–2071. 3. Hong SJ, Lim DS, Seo HS, Kim YH, Shim WJ, Park CG, et al. Percutaneous coronary intervention with drug-eluting stent implantation versus minimally invasive direct coronary artery bypass (MIDCAB) in patients with left anterior descending coronary artery stenosis. Catheter Cardiovasc Interv 2005; 64: 75–81. 4. Ryan TJ, Bauman WB, Kennedy JW, Kereiakes DJ, King SB III, McCallister BD, et al. Guidelines for percutaneous transluminal coronary angioplasty. A 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. 5. Diegeler A, Thiele H, Falk V, Hambrecht R, Spyrantis N, Sick P, 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. 6. Fischman DL, Leon MB, Baim DS, Schatz RA, Savage MP, Penn I, et al. A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease: Stent Restenosis Study Investigators. N Engl J Med 1994; 331: 496–501. 7. Omeroglu SN, Kırali K, Guler M, Toker ME, Ipek G, Is¸ık O¨, et al. Midterm angiographic assessment of coronary artery bypass grafting without cardiopulmonary bypass. Ann Thorac Surg 2000; 70: 844–849. 8. Ankeney JL and Goldstein DJ. Off-pump bypass of the left anterior descending coronary artery 23- to 34- year follow up. J Thorac Cardiovasc Surg 2007; 133: 1499–1503. 9. Moses JW, Leon MB, Popma JJ, Fitzgerald PJ, Holmes DR, O’Shaughnessy C, et al. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med 2003; 349: 1315–1323. 10. Sawhney N, Moses JW, Leon MB, Kuntz RE, Popma JJ, Bachinsky W, et al. Treatment of left anterior descending coronary artery disease with sirolimus-eluting stents. Circulation 2004; 110: 374–379. 11. Dangas G, Ellis SG, Shlofmitz R, Katz S, Fish D, Martin S, et al. Outcomes of paclitaxel-eluting stent implantation
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in patients with stenosis of the left anterior descending coronary artery. J Am Coll Cardiol 2005; 45: 1186–1192. Lemos PA, Saia F, Ligthart JM, Arampatzis CA, Sianos G, Tanabe K, et al. Coronary restenosis after sirolimuseluting stent implantation: morphological description and mechanistic analysis from a consecutive series of cases. Circulation 2003; 108: 257–260. Fajadet J, Morice MC, Bode C, Barragan P, Serruys PW, Wijns W, et al. Maintenance of long-term clinical benefit with sirolimus-eluting coronary stents. Circulation 2005; 111: 1040–1044. Kim JW, Lim DS, Sun K, Shim WJ and Rho YM. Stenting or MIDCAB using ministernotomy for revascularization of proximal left anterior descending artery? Ind J Cardiol 2005; 99: 437–441. Ben-Gal Y, Moshkovitz Y, Nesher N, Uretzky G, Braunstein R, Hendler A, et al. Grafting in patients with diabetes mellitus. Ann Thorac Surg 2006; 82: 1692–1697. Bainbridge D, Cheng D, Martin J and Novick R Evidence-based Peri-operative Clinical Outcomes Research (EPiCOR) Group. Does off-pump or minimally invasive coronary artery bypass reduce mortality, morbidity, and resource utilization when compared with percutaneous coronary intervention? A meta-analysis of randomized trials [Review]. J Thorac Cardiovasc Surg 2007; 133: 623–631. Herz I, Moshkowitz Y, Hendler A, Adam SZ, Uretzky G, Ben-Gal Y, et al. Revascularization of left anterior descending artery with drug-eluting stents: comparison with off-pump surgery. Ann Thorac Surg 2005; 79: 88–92. Etienne PY, Glineur D, Papadatos S, Kalscheuer G, Mairy Y, Boodhwani M, et al. Comparison of minimally invasive direct coronary artery bypass surgery with implantation of drug-eluting stents in patients with left anterior descending coronary artery disease. Innovation (Phila) 2009; 4: 340–344. Jaffery Z, Kowalski M, Weaver WD and Khanal S. A meta-analysis of randomized control trials comparing minimally invasive direct coronary bypass grafting versus percutaneous coronary intervention for stenosis of the proximal left anterior descending artery. Eur J Cardiothorac Surg 2007; 31: 691–697. Thiele H, Neumann-Schniedewind P, Jacobs S, Boudriot E, Walther T, Mohr FW, et al. Randomized comparison of minimally invasive direct coronary artery bypass surgery versus sirolimus-eluting stenting in isolated proximal left anterior descending coronary artery stenosis. J Am Coll Cardiol 2009; 53: 2324–2331.
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Treatment of left anterior descending coronary artery stenosis: stent or surgery
Asian Cardiovascular & Thoracic Annals 21(5) 528–532 ß The Author(s) 2012 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0218492312461262 aan.sagepub.com
Mesut Sismanoglu, Sabit Sarıkaya, Oruc Alper Onk, Taylan Adademir, Eray Aksoy and Kaan Kırali
Abstract Background: Drug-eluting stents have emerged as a solution to the problem of restenosis after bare-metal stent implantation, as an alternative to off-pump coronary bypass, for isolated left anterior descending coronary artery lesions at short-term follow-up. However, long-term follow-up is yet to be defined. Methods: From January to December 2004, 64 consecutive patients underwent myocardial revascularization: 31 by drug-eluting stents and 33 by off-pump coronary bypass. The primary endpoint was angiographic outcome, and the secondary endpoint was clinical outcome at 5 years. Results: There was no early or late mortality in either group. Hospital stay was significantly shorter in the stent group (2.5 2.1 vs. 7.1 4.9 days, p ¼ 0.003). Long-term patency was higher and major adverse cardiac events (recurrence of angina and revascularization of target vessel) were encountered less frequently in the coronary bypass group, although not significantly. Conclusion: The 5-year follow-up showed no significant difference between the off-pump coronary bypass and stent groups for the primary and secondary endpoints. As a significant difference between treatment options is lacking, decision-making for appropriate treatment in this group of patients requires the collaboration of cardiologists and cardiovascular surgeons and an individual approach, to achieve successful long-term outcomes.
Keywords Coronary artery bypass, off-pump, coronary artery disease, drug-eluting stents, heart catheterization, treatment outcome
Introduction
Patients and methods
Percutaneous intervention and off-pump coronary artery bypass (OPCAB) are both well-accepted treatment options for isolated high-grade stenosis of the proximal left anterior descending (LAD) coronary artery. Randomized trials comparing bare metal stenting with OPCAB surgery have shown a significantly higher reintervention rate for stenting and similar results for mortality and reinfarction.1 Drug-eluting stents (DES) have emerged as a solution to the problem of restenosis after bare-metal stent implantation, but there are only a few reports comparing early results of DES and OPCAB for isolated LAD stenosis.2,3 We report the 5-year results of a trial comparing surgical revascularization with the left internal mammary artery (LIMA) and intracoronary DES in patients with proximal LAD stenosis.
This prospective non-randomized study was approved by the local ethics committee. Patients with chronic stable angina pectoris caused by an isolated proximal LAD lesion (>70% stenosis, no total occlusion) were selected from January 2004 to December 2004 in Kartal Kosuyolu Heart and Research Hospital. Patients who were eligible for both OPCAB and percutaneous angioplasty with primary stenting were asked to choose one
Department of Cardiovascular Surgery, Kosuyolu Heart and Research Hospital, Istanbul, Turkey Corresponding author: Kaan Kırali, MD, Kartal Kos¸uyolu Yu¨ksek Ihtisas Eg˘itim ve Aras¸tırma Hastanesi, Kartal, Istanbul 34846, Turkey. Email: [email protected]
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of the treatment protocols. After written informed consent was obtained, the patients were assigned to stenting or surgery. Exclusion criteria were acute coronary syndromes, additional significant coronary lesions, valvular heart disease, gastrointestinal intolerance to anticoagulant treatment, and previous interventional or surgical treatment for coronary artery disease. There were 64 patients who met the inclusion criteria; 31 of them wanted to have stent placement and 33 chose to undergo OPCAB. The baseline demographic and angiographic characteristics of patients were similar, but those in the OPCAB group were significantly younger and had less family history of coronary artery disease (Table 1). OPCAB was performed through a median sternotomy without cardiopulmonary bypass. The LIMA was harvested and the LIMA-LAD anastomosis was carried out during heparinization (activated clotting time >300 s) on a beating heart, using a running 7/0 Prolene suture, with the help of a mechanical coronary stabilizer (Genzyme Immobilizer System; Teleflex Medical, Research Triangle Park, NC, USA) and temporary occlusion of the LAD with a proximal snare. Heparin was neutralized with a 2/1 ratio of protamine at the end of the procedure. All patients received 150 mg of aspirin daily, starting on postoperative day 1. For stent implantation, a coronary guiding catheter of 6 F to 8 F was used to access the coronary arteries through the femoral approach. After predilatation, the optimal DES was implanted at the target site, covering the entire lesion. A narrowing of 0% by visual estimation or 20% by quantitative coronary angiography with TIMI grade 3 distal flow was the goal. All patients were pretreated with 300 mg of aspirin and 600 mg of clopidogrel 24 h before angioplasty with stenting. A bolus of 10,000 IU of heparin was administered intravenously after sheath insertion (activated clotting time >300 s).
No protamine was given at the end of the procedure. All patients received 100 mg of aspirin and 75 mg of clopidogrel daily from stent implantation until 1 year after the procedure. In both groups, patients had electrocardiographic monitoring during the first 24 h after the procedure, and creatine kinase and creatine kinase-MB levels were estimated during the first 3 days. A 12-lead electrocardiogram was obtained daily or when clinically required. All patients were followed up for 5 years until their preplanned coronary angiography. The primary endpoint of the study was the 5-year angiographic follow-up. Secondary endpoints were major adverse cardiac and cerebrovascular events (MACCE), status of angina pectoris, use of medication, need for repeat target vessel revascularization, and hospitalization time. Five years after the initial procedure, quantitative coronary angiography was performed. From 2 orthogonal views, the percentage of the diameter of stenosis was calculated as a mean. Successful revascularization in the OPCAB group was defined as a percentage stenosis diameter of the anastomosis of less than 50% of the mid-LITA diameter, and in the stent group, as the percentage of the diameter of stenosis in the stented segment of less than 50% of the reference diameter of the LAD. The quality of the revascularization of the target vessel was graded as: no abnormalities or small irregularities; nonsignificant stenosis (20%–50% luminal stenosis); or stenotic (>50% luminal stenosis).4 This study was powered to evaluate the 5-year eventfree survival of the ongoing study. For evaluation of the angiographic outcome in this study, an analysis was planned for the first 64 patients. For this analysis, no formal sample size calculation was performed. Statistical analysis was undertaken in accordance with the intention-to-treat principle. In this setting, patients
Table 1. Baseline characteristics of 64 patients undergoing OPCAB or stenting. Variable
Stenting (n ¼ 31)
OPCAB (n ¼ 33)
p value
Age (years) Family history of CAD Sex (male/female) Smoking History of MI Diabetes mellitus Hypertension Hypercholesterolemia Chronic renal failure LV dysfunction
57.2 11.7 18 (56.3%) 22/10 11 (34.4%) 14 (43.8%) 6 (18.8%) 17 (53.1%) 11 (34.4%) 2 (6.1%) 11 (34.4%)
50.5 11.5 8 (23.5%) 20/13 14 (41.2%) 20 (58.8%) 12(35.3%) 22 (64.7%) 11 (32.4%) 3 (8.8%) 12 (32.4%)
0.03 0.01 0.58 0.62 0.62 0.17 0.45 0.86 1 0.86
CAD: coronary artery disease; LV: left ventricular; MI: myocardial infarction; OPCAB: off-pump coronary artery bypass.
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were evaluated on the basis of the treatment they chose. The baseline descriptive statistics for continuous variables are given as the mean and standard error. For normally distributed continuous variables, the differences between the 2 strategies were evaluated with Student’s t test. For continuous endpoints with a skewed distribution, 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. Fisher’s exact test or the chi-squared test was used to evaluate the differences between surgical intervention and stenting. The quantitative coronary angiography outcomes of both treatments at the 5-year follow-up were evaluated with the chi-squared test. For all analyses, commercially available computer software (Statistical Package for Social Sciences, release 16.0; SPSS, Inc., Chicago, IL, USA) was used.
Results No patient in the stent group crossed over to OPCAB and vice versa. There was no early mortality in either group. OPCAB was performed as planned in all patients, and the operations were uneventful. Bleeding that required reintervention occurred in 1 (3.0%) patient and blood transfusion was necessary in 7 (21.2%). The mean length of hospital stay was 7.1 4.9 days (range, 4–26 days). In the stent group, the mean length of hospital stay was 2.5 2.1 days (range, 1–9 days; p ¼ 0.003). One (3.2%) patient had a myocardial infarction after stenting as a result of occlusion of a diagonal branch, and groin bleeding requiring blood transfusion occurred in 2 (6.5%). The mean follow-up was 5.2 0.9 years. There was no mortality at the end of 5 years in either group. Follow-up quantitative angiography was performed in all patients. In 93.9% (31/33 patients) of OPCAB patients, patency of the LIMA graft was noted, and 5 (16.1%) in the stent group had restenosis defined as 50% or more stenosis (p ¼ 0.19; Table 2). In the OPCAB group, one patient was treated by conventional angioplasty by placement of a stent within the LIMA, and another underwent coronary artery bypass grafting. In the stent group, 3 patients were treated by conventional angioplasty (placement of a second stent within the first one) and 2 underwent coronary artery bypass grafting. The Canadian Cardiovascular Society angina class of the treatment groups revealed no differences at the end of the 5-year follow-up (Table 3): 28 (84.8%) patients in the OPCAB group and 22 (71%) in the stent group were in class 0 or 2 (p > 0.05). Only 5 patients in the OPCAB group were in class II or III compared with 9 in the stent group (p > 0.05). At the end of the 5-year follow-up, antianginal drugs were
prescribed to 15% of the patients treated by OPCAB and to 30% of those treated by stent implantation (p > 0.05). The quality of revascularization of the target vessel at the end of 5 years seemed better in the OPCAB group (Table 4), but the difference was not statistically significant.
Discussion We found that both revascularization strategies were safe and effective up to the 5-year follow-up. Although the differences were not significant, trends favoring surgery were observed in clinical improvement and quality of revascularization. Bare-metal stent revascularization of proximal LAD lesions has a 29%–44% restenosis rate.5,6 DES emerged as a solution to this problem, as an alternative to OPCAB which has more than 90% LIMA-LAD longterm patency.7,8 Both restenosis and reintervention rates have reduced significantly with the use of DES. Although higher restenosis rates were reported in diabetic patients with small and complex lesions (that might also impair results of surgery), restenosis rates
Table 2. Adverse events during follow-up. Event
Stenting (n ¼ 31)
OPCAB (n ¼ 33)
Death Nonfatal myocardial infarction Cerebrovascular accident Recurrent AP Repeat revascularization Hospitalization for unstable AP MACCE
0 3 (9.7%) 0 14 (45.2%) 5 (16.1%) 3 (9.7%) 7 (22.5%)
0 3 0 8 2 3 4
p value
(9.1%)
0.66
(24.5%) (6.1%) (9.1%) (12.2%)
0.06 0.19 0.66 0.23
AP: angina pectoris; MACCE: major adverse cardiac and cerebrovascular events; OPCAB: off-pump coronary artery bypass.
Table 3. Canadian Cardiovascular Society angina class at 5 years. CCS class
Stenting (n ¼ 31)
OPCAB (n ¼ 33)
0 1 2 3 4
17 (54.8%) 5 (16.1%) 6 (19.4%) 3 (9.7%) 0
25 (75.7%) 3 (9.1%) 2 (6.1%) 3 (9.1%) 0
p value >0.05 >0.05 >0.05 >0.05
CCS: Canadian Cardiovascular Society; OPCAB: off-pump coronary artery bypass.
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Table 4. Quality of revascularization of the target vessel at 5 years. Quality
Stenting (n ¼ 31)
OPCAB (n ¼ 33)
p value
No abnormalities Nonsignificant stenosis (20%–50%) Stenosis (>50%)
17 (54,8%) 9 (29.1%) 5 (16.1%)
25 (75.7%) 6 (18.2%) 2 (6.1%)
>0.05 >0.05 >0.05
OPCAB: off-pump coronary artery bypass.
are no more than 10% in the short term.9–13 There are limited data comparing DES and OPCAB in the long term. In our study, OPCAB had a slightly better angiographic outcome than DES at the 5-year follow-up. Five-year follow-up coronary angiography reveled 83.9% patency after DES and 93.9% after OPCAB (p ¼ 0.19). There was no early or late mortality in either group. Mean hospitalization time after OPCAB was 7.1 4.9 days, and that after stenting was 2.5 2.1 days. This shorter convalescence period reflects the true minimally invasive character of stenting, as shown in other studies.14 Periprocedural complications, MACCE, angina class, or use of antianginal medication did not differ significantly between groups. Studies comparing DES and OPCAB for recurrence of angina favor surgery with increasing follow-up time.3,15–19 At 5 years, 54.8% of patients with DES and 75.5% of those with OPCAB had angina-free survival. Hong and colleagues3 revealed 1.7% repeat target vessel revascularization after DES and 5.9% after surgery at 6 months of follow-up. Other studies with longer follow-up time have favored surgery.15,17 Etienne and colleagues18 noted revascularization rates of 13.6% and 2.6% for DES and surgery, respectively, after 2 years. In our study, 14 (45.2%) of the patients with DES had some degree of restenosis whereas 8 (24.3%) cases of restenosis were seen after surgery. Although repeat target vessel revascularization did not differ significantly at 5 years, a difference can be expected after longer follow-up. A recent meta-analysis by Jaffery and colleagues19 showed similar periprocedural myocardial infarction rates for stenting and surgery. Three patients in each group suffered myocardial infarction in our study. MACCE rates also favored surgery in our study (22.5% vs. 12.2%). A study comparing sirolimus-eluting stenting vs. minimally invasive direct coronary bypass grafting surgery revealed 7.7% MACCE rates for both groups at 12 months, most probably due to a high rate of myocardial infarction after surgery.20 Other studies have favored surgery on the basis of MACCE rates.3,15,17–19 Ben-Gal and colleagues2 showed MACCE rates of 21% for DES and 6% for surgery at 2 years. Treatment of isolated high-grade stenosis of the LAD with DES is less invasive, requires a shorter hospital stay, and is usually associated with less acute morbidity compared to standard coronary artery
bypass surgery. OPCAB surgery is an acceptable alternative to standard coronary artery bypass grafting. The quality of coronary anastomoses is the main concern in OPCAB surgery, due to the need to perform anastomoses on a beating heart with a temporarily occluded coronary artery. Studies have demonstrated that OPCAB appears to give similar anastomotic patency to conventional coronary artery bypass grafting. The major advantage of OPCAB is avoidance of cardiopulmonary bypass. Despite the advantages, OPCAB is technically demanding and still more invasive than stenting, with a longer mean hospital stay (7.1 vs. 2.5 days in this study). Although the difference was not significant, there were more patients with restenosis and repeat revascularization in the DES group at 5 years. Use of glycoprotein 2b/3a inhibitors might decrease the restenosis rate in these patients. In our study, there was still a trend in favor of surgery, which at longer follow-up might be further attenuated. The rates of complete angina relief, restenosis, and MACCE were better with OPCAB surgery. In conclusion, patients with isolated LAD coronary artery stenosis can be treated safely with OPCAB or DES placement. DES remains hampered by the risk of restenosis and need for repeated revascularization. Stenting may be more suitable for some lesions with a low to intermediate restenosis risk, whereas surgery may provide excellent outcomes regardless of lesion morphology, including chronic total occlusion. Therefore, each lesion requires an interdisciplinary approach for selection of the best treatment option. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Conflicts of interest statement None declared.
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