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The emerging role of percutaneous coronary intervention in the management of unprotected left main coronary artery disease: Ongoing debate
90
Letters to the Editor
The emerging role of percutaneous coronary intervention in the management of unprotected left main coronary artery disease: Ongoing debate Turgay Celik ⁎ Atila Iyisoy Gulhane Military Medical Academy, School of Medicine, Department of Cardiology, Etlik-Ankara, Turkey Received 24 September 2008; accepted 13 December 2008 Available online 21 January 2009
Keywords: Coronary stents; Left main coronary artery; Percutaneous coronary intervention
In their recently published well-presented article, Wu et al. tried to evaluate the in-hospital, 30 day and long-term outcomes after percutaneous coronary intervention (PCI) for unprotected left main coronary artery (LMCA) disease [1]. In that retrospective study, 55 consecutive patients with N 50% diameter stenosis of LMCA undergoing PCI were analyzed. The procedural success rate was 98%. Seventyfive percent of the patients underwent drug-eluting stent (DES) implantation. The majority of cases were treated with a double-stent strategy. There were no in-hospital deaths. The mean clinical follow-up time was 867 ± 410 days. Twenty-nine percent of the patients experienced major adverse cardiac events (MACE), including 3 (5%) deaths, 4 (7%) myocardial infarctions (MI), and 12 (21.8%) target lesion revascularizations (TLR) during follow-up. Multivariate analysis revealed that hyperlipidemia (hazard ratio, HR = 6.2) and bifurcation involvement (HR = 4.4) were independent predictors for MACE. They concluded that PCI with stenting was an acceptable treatment option for patients with LMCA stenosis and involvement of the LMCA bifurcation remains a predictor for unfavorable outcome. Left main coronary artery disease in a patient with symptomatic coronary disease is usually treated by coronary artery bypass graft surgery (CABG) associated with a significant improvement in outcome compared to medical therapy [2]. Percutaneous coronary intervention has usually been restricted to patients who are considered inoperable, are at high risk for CABG, or have had a prior CABG with at least one patent graft to the left anterior descending or circumflex artery (so-called “protected” left main disease) because of the potential consequences of a complication such as acute vessel closure [3]. Reduced rates of restenosis with DES may make LMCA stenting more feasible in the future. With improved stenting
⁎ Corresponding author. Tel.: +90 312 3044268; fax: +90 312 3044250. E-mail address: [email protected] (T. Celik).
techniques and the availability of DES, stenting of unprotected LMCA disease is accepted as a more routine strategy [4]. There is increasing evidence of improved outcomes with PCI using DES compared to bare metal stents (BMS) in LMCA disease [5–8]. In the largest reported experience, 102 consecutive patients with de novo unprotected LMCA stenosis received a sirolimus-eluting stent (SES); the outcomes were compared to those in 121 patients receiving BMS [5]. Though less acute gain in vessel diameter, the SES was associated with significant reductions in the degree of late lumen loss, angiographic restenosis at 6 months (7 versus 30%), and the target vessel revascularization at 1 year (2 versus 17%). In another study, 95 patients with de novo LMCA disease receiving a DES; the outcomes were compared to those in 86 patients receiving a BMS [6]. At a median follow-up of 503 days, patients receiving a DES had a significantly lower rate of MACE. On multivariate analysis, the use of a DES was an independent predictor of better cardiovascular outcomes. The hypothesis was whether or not DES-PCI would be non-inferior to CABG in the management of patients with 3-vessel disease and/or LMCA disease in The Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) trial [9]. In that study a total of 1800 patients were randomized, 897 to CABG and 903 to DES-PCI. About 28.3% were diabetic, with 33% having evidence of prior MI. Unstable angina was present in about 28.5% of the patients, and the additive mean EuroSCORE was 3.8. The mean number of lesions was about 4.4, with about 66% having 3-vessel disease only (without LMCA involvement), and 3.4% having pure LMCA disease. LMCA + 1-, 2-, and 3-vessel disease was present in about 5.3%, 11.8%, and 13.7% of the patients, respectively. The number of bifurcation and trifurcation lesions was similar between the two groups. Of the patients undergoing PCI, the mean number of stents implanted was 4.6, with an average of 3.6 lesions being treated per patient. About 15% of the patients in the CABG arm underwent off-pump CABG; at least one arterial graft was used in 97.3% of the patients (95.6% with
Letters to the Editor
an arterial graft to the left anterior descending). The mean number of grafts per patient was 2.8. The incidence of the primary endpoint of major adverse cardiac and cerebrovascular events (MACCE) at 12 months was lower in the CABG arm compared with PCI (12.1% vs. 17.8%), and did not meet the prespecified non-inferiority threshold for PCI. This was driven predominantly by a significant reduction in the incidence of repeat revascularization in the CABG arm compared with PCI (5.9% vs. 13.7%). There was no difference in the incidence of death or myocardial infarction between the two treatment arms. The incidence of cerebrovascular accident was significantly higher in the CABG arm (2.2% vs. 0.6%), whereas the incidence of symptomatic graft occlusion and stent thrombosis was similar between arms. On subgroup analysis of the LMCA patients, the overall 12-month MACCE event rate was lower with CABG (13.7% vs. 15.8%), although patients with LMCA only (8.5% vs. 7.1%) and LMCA + 1-vessel disease (13.2% vs. 7.5%) seemed to do slightly better with PCI. Patients with LMCA + 2-vessel disease (14.4% vs. 19.8%), LMCA + 3vessel disease (15.4% vs. 19.4%), or 3-vessel disease alone (11.5% vs. 19.2%) seemed to do better with CABG than PCI. When stratified by diabetes status, patients with diabetes had lower 12-month MACCE event rates with CABG than with PCI (14.2% vs. 26.0%), whereas nondiabetic patients showed a trend toward a benefit with CABG, but it was not statistically significant. The results of the SYNTAX trial demonstrate that in patients with LMCA disease and/or severe 3-vessel disease, CABG (with the use of at least one arterial graft) is superior to PCI with TAXUS DES. This is especially true for reducing 12-month MACCE rates, which were predominantly driven by the need for repeat revascularization in the PCI arm. CABG is, however, associated with a higher risk of CVA at 12 months, compared with PCI. More importantly, there is no difference in the incidence of death, MI, or graft occlusion/stent thrombosis between the two arms. The largest benefit from CABG seems to be in patients with diabetes mellitus. The results of this trial also suggest that patients with LMCA only, LMCA + 1-vessel disease, and nondiabetics may do as well with both CABG and PCI, although the trial was not powered to examine these differences individually. In conclusion, LMCA-PCI can be offered as an option to patients at higher surgical risk who have ostial or mid-shaft rather than bifurcation lesions and to all patients who refuse CABG. Reduced rates of restenosis with DES may make LMCA stenting more feasible in the future and there is increasing evidence of improved outcomes with PCI using DES compared to BMS in LMCA disease. Some recent studies such as DES-DIABETES, SIRTAX, and ISARDIABETES have suggested that SESs may be associated
0167-5273/$ - see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2008.12.058
91
with better outcomes in diabetic patients compared with paclitaxel-eluting stents (PES). It is unknown whether the use of SES instead of PES, or new generation stents such as everolimus-eluting stents, would be associated with better outcomes in patients with LMCA disease undergoing PCI. We strongly believe that further long-term follow-up results of those trials, as well as the results of other ongoing trials on this topic (e.g., FREEDOM, PRE-COMBAT) will elucidate the place of PCI in the management of LMCA disease. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [10]. References [1] Wu XM, Liu CP, Lin WC, Kao HL. Long-term outcome of percutaneous coronary intervention for unprotected left main coronary artery disease. Int J Cardiol 2008;130:185–9. [2] Eagle KA, Guyton RA, Davidoff R, et al. ACC/AHA 2004 guideline update for coronary artery bypass graft surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1999 Guidelines for Coronary Artery Bypass Graft Surgery). Circulation 2004;110:e340–437. [3] Smith Jr SC, Feldman TE, Hirshfeld Jr JW, et al. ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/SCAI Writing Committee to Update the 2001 Guidelines for Percutaneous Coronary Intervention). J Am Coll Cardiol 2006;47:e1–e121. [4] Cutlip D. Management of left main coronary artery disease. In: Rose BD, editor. UpToDate. Wellesley: UpToDate; 2007. [5] Park SJ, Kim YH, Lee BK, et al. Sirolimus-eluting stent implantation for unprotected left main coronary artery stenosis Comparison with bare metal stent implantation. J Am Coll Cardiol 2005;45:351–6. [6] Valgimigli M, van Mieghem CA, Ong AT, et al. Short- and long-term clinical outcome after drug-eluting stent implantation for the percutaneous treatment of left main coronary artery disease: insights from the Rapamycin-Eluting and Taxus Stent Evaluated At Rotterdam Cardiology Hospital registries (RESEARCH and T-SEARCH). Circulation 2005;111:1383–9. [7] Chieffo A, Stankovic G, Bonizzoni E, et al. Early and mid-term results of drug-eluting stent implantation in unprotected left main. Circulation 2005;111:791–5. [8] Arampatzis CA, Lemos PA, Tanabe K, et al. Effectiveness of sirolimus-eluting stent for treatment of left main coronary artery disease. Am J Cardiol 2003;92:327–9. [9] The Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery: the SYNTAX Study. Presented by Dr. Patrick Serruys at the European Society of Cardiology Congress, Munich, Germany, August/September; 2008. [10] Coats AJ. Ethical authorship and publishing. Int J Cardiol 2009;131:149–50.
Letters to the Editor
The emerging role of percutaneous coronary intervention in the management of unprotected left main coronary artery disease: Ongoing debate Turgay Celik ⁎ Atila Iyisoy Gulhane Military Medical Academy, School of Medicine, Department of Cardiology, Etlik-Ankara, Turkey Received 24 September 2008; accepted 13 December 2008 Available online 21 January 2009
Keywords: Coronary stents; Left main coronary artery; Percutaneous coronary intervention
In their recently published well-presented article, Wu et al. tried to evaluate the in-hospital, 30 day and long-term outcomes after percutaneous coronary intervention (PCI) for unprotected left main coronary artery (LMCA) disease [1]. In that retrospective study, 55 consecutive patients with N 50% diameter stenosis of LMCA undergoing PCI were analyzed. The procedural success rate was 98%. Seventyfive percent of the patients underwent drug-eluting stent (DES) implantation. The majority of cases were treated with a double-stent strategy. There were no in-hospital deaths. The mean clinical follow-up time was 867 ± 410 days. Twenty-nine percent of the patients experienced major adverse cardiac events (MACE), including 3 (5%) deaths, 4 (7%) myocardial infarctions (MI), and 12 (21.8%) target lesion revascularizations (TLR) during follow-up. Multivariate analysis revealed that hyperlipidemia (hazard ratio, HR = 6.2) and bifurcation involvement (HR = 4.4) were independent predictors for MACE. They concluded that PCI with stenting was an acceptable treatment option for patients with LMCA stenosis and involvement of the LMCA bifurcation remains a predictor for unfavorable outcome. Left main coronary artery disease in a patient with symptomatic coronary disease is usually treated by coronary artery bypass graft surgery (CABG) associated with a significant improvement in outcome compared to medical therapy [2]. Percutaneous coronary intervention has usually been restricted to patients who are considered inoperable, are at high risk for CABG, or have had a prior CABG with at least one patent graft to the left anterior descending or circumflex artery (so-called “protected” left main disease) because of the potential consequences of a complication such as acute vessel closure [3]. Reduced rates of restenosis with DES may make LMCA stenting more feasible in the future. With improved stenting
⁎ Corresponding author. Tel.: +90 312 3044268; fax: +90 312 3044250. E-mail address: [email protected] (T. Celik).
techniques and the availability of DES, stenting of unprotected LMCA disease is accepted as a more routine strategy [4]. There is increasing evidence of improved outcomes with PCI using DES compared to bare metal stents (BMS) in LMCA disease [5–8]. In the largest reported experience, 102 consecutive patients with de novo unprotected LMCA stenosis received a sirolimus-eluting stent (SES); the outcomes were compared to those in 121 patients receiving BMS [5]. Though less acute gain in vessel diameter, the SES was associated with significant reductions in the degree of late lumen loss, angiographic restenosis at 6 months (7 versus 30%), and the target vessel revascularization at 1 year (2 versus 17%). In another study, 95 patients with de novo LMCA disease receiving a DES; the outcomes were compared to those in 86 patients receiving a BMS [6]. At a median follow-up of 503 days, patients receiving a DES had a significantly lower rate of MACE. On multivariate analysis, the use of a DES was an independent predictor of better cardiovascular outcomes. The hypothesis was whether or not DES-PCI would be non-inferior to CABG in the management of patients with 3-vessel disease and/or LMCA disease in The Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) trial [9]. In that study a total of 1800 patients were randomized, 897 to CABG and 903 to DES-PCI. About 28.3% were diabetic, with 33% having evidence of prior MI. Unstable angina was present in about 28.5% of the patients, and the additive mean EuroSCORE was 3.8. The mean number of lesions was about 4.4, with about 66% having 3-vessel disease only (without LMCA involvement), and 3.4% having pure LMCA disease. LMCA + 1-, 2-, and 3-vessel disease was present in about 5.3%, 11.8%, and 13.7% of the patients, respectively. The number of bifurcation and trifurcation lesions was similar between the two groups. Of the patients undergoing PCI, the mean number of stents implanted was 4.6, with an average of 3.6 lesions being treated per patient. About 15% of the patients in the CABG arm underwent off-pump CABG; at least one arterial graft was used in 97.3% of the patients (95.6% with
Letters to the Editor
an arterial graft to the left anterior descending). The mean number of grafts per patient was 2.8. The incidence of the primary endpoint of major adverse cardiac and cerebrovascular events (MACCE) at 12 months was lower in the CABG arm compared with PCI (12.1% vs. 17.8%), and did not meet the prespecified non-inferiority threshold for PCI. This was driven predominantly by a significant reduction in the incidence of repeat revascularization in the CABG arm compared with PCI (5.9% vs. 13.7%). There was no difference in the incidence of death or myocardial infarction between the two treatment arms. The incidence of cerebrovascular accident was significantly higher in the CABG arm (2.2% vs. 0.6%), whereas the incidence of symptomatic graft occlusion and stent thrombosis was similar between arms. On subgroup analysis of the LMCA patients, the overall 12-month MACCE event rate was lower with CABG (13.7% vs. 15.8%), although patients with LMCA only (8.5% vs. 7.1%) and LMCA + 1-vessel disease (13.2% vs. 7.5%) seemed to do slightly better with PCI. Patients with LMCA + 2-vessel disease (14.4% vs. 19.8%), LMCA + 3vessel disease (15.4% vs. 19.4%), or 3-vessel disease alone (11.5% vs. 19.2%) seemed to do better with CABG than PCI. When stratified by diabetes status, patients with diabetes had lower 12-month MACCE event rates with CABG than with PCI (14.2% vs. 26.0%), whereas nondiabetic patients showed a trend toward a benefit with CABG, but it was not statistically significant. The results of the SYNTAX trial demonstrate that in patients with LMCA disease and/or severe 3-vessel disease, CABG (with the use of at least one arterial graft) is superior to PCI with TAXUS DES. This is especially true for reducing 12-month MACCE rates, which were predominantly driven by the need for repeat revascularization in the PCI arm. CABG is, however, associated with a higher risk of CVA at 12 months, compared with PCI. More importantly, there is no difference in the incidence of death, MI, or graft occlusion/stent thrombosis between the two arms. The largest benefit from CABG seems to be in patients with diabetes mellitus. The results of this trial also suggest that patients with LMCA only, LMCA + 1-vessel disease, and nondiabetics may do as well with both CABG and PCI, although the trial was not powered to examine these differences individually. In conclusion, LMCA-PCI can be offered as an option to patients at higher surgical risk who have ostial or mid-shaft rather than bifurcation lesions and to all patients who refuse CABG. Reduced rates of restenosis with DES may make LMCA stenting more feasible in the future and there is increasing evidence of improved outcomes with PCI using DES compared to BMS in LMCA disease. Some recent studies such as DES-DIABETES, SIRTAX, and ISARDIABETES have suggested that SESs may be associated
0167-5273/$ - see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2008.12.058
91
with better outcomes in diabetic patients compared with paclitaxel-eluting stents (PES). It is unknown whether the use of SES instead of PES, or new generation stents such as everolimus-eluting stents, would be associated with better outcomes in patients with LMCA disease undergoing PCI. We strongly believe that further long-term follow-up results of those trials, as well as the results of other ongoing trials on this topic (e.g., FREEDOM, PRE-COMBAT) will elucidate the place of PCI in the management of LMCA disease. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [10]. References [1] Wu XM, Liu CP, Lin WC, Kao HL. Long-term outcome of percutaneous coronary intervention for unprotected left main coronary artery disease. Int J Cardiol 2008;130:185–9. [2] Eagle KA, Guyton RA, Davidoff R, et al. ACC/AHA 2004 guideline update for coronary artery bypass graft surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1999 Guidelines for Coronary Artery Bypass Graft Surgery). Circulation 2004;110:e340–437. [3] Smith Jr SC, Feldman TE, Hirshfeld Jr JW, et al. ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/SCAI Writing Committee to Update the 2001 Guidelines for Percutaneous Coronary Intervention). J Am Coll Cardiol 2006;47:e1–e121. [4] Cutlip D. Management of left main coronary artery disease. In: Rose BD, editor. UpToDate. Wellesley: UpToDate; 2007. [5] Park SJ, Kim YH, Lee BK, et al. Sirolimus-eluting stent implantation for unprotected left main coronary artery stenosis Comparison with bare metal stent implantation. J Am Coll Cardiol 2005;45:351–6. [6] Valgimigli M, van Mieghem CA, Ong AT, et al. Short- and long-term clinical outcome after drug-eluting stent implantation for the percutaneous treatment of left main coronary artery disease: insights from the Rapamycin-Eluting and Taxus Stent Evaluated At Rotterdam Cardiology Hospital registries (RESEARCH and T-SEARCH). Circulation 2005;111:1383–9. [7] Chieffo A, Stankovic G, Bonizzoni E, et al. Early and mid-term results of drug-eluting stent implantation in unprotected left main. Circulation 2005;111:791–5. [8] Arampatzis CA, Lemos PA, Tanabe K, et al. Effectiveness of sirolimus-eluting stent for treatment of left main coronary artery disease. Am J Cardiol 2003;92:327–9. [9] The Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery: the SYNTAX Study. Presented by Dr. Patrick Serruys at the European Society of Cardiology Congress, Munich, Germany, August/September; 2008. [10] Coats AJ. Ethical authorship and publishing. Int J Cardiol 2009;131:149–50.