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Comparison of Clinical Outcomes of Overlapping Sirolimus- Versus Paclitaxel-Eluting Stents in Patients Undergoing Percutaneous Coronary Intervention
Comparison of Clinical Outcomes of Overlapping Sirolimus- Versus Paclitaxel-Eluting Stents in Patients Undergoing Percutaneous Coronary Intervention William W. Chu, MD, PhD, Pramod K. Kuchulakanti, MD, Rebecca Torguson, BS, Betty Wang, PhD, Leonardo C. Clavijo, MD, PhD, William O. Suddath, MD, Augusto D. Pichard, MD, Lowell F. Satler, MD, Kenneth M. Kent, MD, PhD, and Ron Waksman, MD* Sirolimus-eluting stent (SES) and paclitaxel-eluting stent (PES) implantation for the treatment of single coronary lesions has proved to be effective and durable. However, the safety and efficacy of overlapping drug-eluting stents for the treatment of long lesions have not been well established. In total, 114 patients who received overlapping drug-eluting stents were identified, 55 of whom received overlapping SESs and 59 received overlapping PESs. Baseline clinical and angiographic characteristics were balanced. In-hospital complications were similar between the 2 groups. At 30-day and 6-month follow-ups, all clinical outcomes were also similar. In addition, the event-free survival rate was comparable (p ⴝ 0.71). Implantation of overlapping drug-eluting stents for the treatment of long, native coronary lesions is feasible and effective. In conclusion, in this observational study, clinical outcomes appeared similar in patients treated with overlapping SES implantation compared with those treated with overlapping PES implantation. © 2006 Elsevier Inc. All rights reserved. (Am J Cardiol 2006;98:1563–1566) Since the era of balloon angioplasty, stents have been a revolutionary advance in the treatment of severe coronary artery disease in the field of interventional cardiology. However, the high restenotic and repeat revascularization rates in patients treated with bare metal stents have been a major problem, especially in long coronary lesions.1,2 Drug-eluting stents have been proved to significantly decrease restenotic rates and the need for repeat revascularization in discrete de novo lesions in pivotal randomized clinical studies. Regulatory agencies in the United States and Europe have approved the sirolimus-eluting stent (SES) and paclitaxel-eluting stent (PES) for marketing based on their safety and performance in the decrease of restenosis based on these trials.3–7 The approved indication of drug-eluting stents is limited to stents of 2.5 to 3.5 mm in diameter with lengths up to 32 mm. However, long diffuse lesions often require overlapping stent implantation to cover the entire lesion segment. Data from head-to-head comparisons of the 2 stents examined in numerous randomized clinical trials are conflicting. The Prospective, Randomized Multi-Center Comparison of the Cypher Sirolimus-Eluting and the Taxus Paclitaxel-Eluting Stent Systems (REALITY) Study,8 a 1,353-patient trial, demonstrated that binary restenotic rate, death, myocardial infarction, target lesion revascularization, and target vessel revascularization were similar between the SES and PES systems, whereas the Sirolimus-eluting and
Division of Cardiology, Washington Hospital Center, Washington, DC. Manuscript received May 4, 2006; revised manuscript received and accepted July 3, 2006. *Corresponding author: Tel: 202-877-8575; fax: 202-877-2715. E-mail address: [email protected] (R. Waksman). 0002-9149/06/$ – see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2006.07.032
Paclitaxel-eluting Stents for Coronary Revascularization (SIRTAX) Study,9 a 1,012-patient trial, showed favorable results in the SES arm in terms of target lesion revascularization, late lumen loss, and binary restenosis. Data on overlapping PESs for long lesions in the Taxus V study were alarming. It showed an increase in creatine kinase and myonecrosis in the Taxus stent compared with the bare metal stent.10 Limited information is available on overlapping SESs for diffuse lesions, and a comparison of overlapping SESs versus PESs in treating long lesions is not available. To further pursue this interesting subject, we conducted this retrospective analysis to compare the clinical outcomes of overlapping SES and PES implantation. Methods and Results We retrospectively analyzed patients who underwent percutaneous coronary intervention (PCI) with SESs (Cypher, Johnson & Johnson Cordis Corp., Miami, Florida) and PESs (Taxus, Boston Scientific Corp., Natick, Massachusetts) at Washington Hospital Center (Washington, DC). Since approval of SESs and PESs by the Food and Drug Administration, 114 patients who underwent overlapping drug-eluting stent implantation for native coronary lesions were identified, 55 (104 lesions) of whom received overlapping SES implantation with ⬎1-mm overlap (overlapping SES group) and 59 (105 lesions) received overlapping PES implantation with ⬎1-mm overlap (overlapping PES group). In the 2 study groups, patients who presented with acute myocardial infarction and cardiogenic shock were excluded. Coronary angioplasty was performed according to standard percutaneous techniques using the femoral approach and standard techniques for stent implantation. All patients www.AJConline.org
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Table 1 Baseline clinical characteristics of the study population Variable
Overlapping SES (n ⫽ 55)
Overlapping PES (n ⫽ 59)
p Value
Age (yrs) Men Diabetes mellitus Systemic hypertension Hyperlipidemia Chronic renal insufficiency Smoker Ejection fraction
62.9 ⫾ 12.3 41 (74.5%) 24 (43.6%) 46 (83.6%) 48 (87.3%) 5 (9.1%) 6 (10.9%) 0.52 ⫾ 0.13
66.3 ⫾ 11.0 38 (64.4%) 18 (30.5%) 46 (78.0%) 48 (81.4%) 8 (13.6%) 9 (15.3%) 0.49 ⫾ 0.14
0.16 0.24 0.15 0.44 0.39 0.45 0.49 0.21
Table 2 Angiographic and procedural characteristics of the study population Variable
Left main coronary artery Left anterior descending coronary artery Left circumflex coronary artery Right coronary artery Saphenous vein graft Proximal lesion Mid-lesion Distal lesion Ostial lesion Restenotic lesion Type C lesion Stent diameter (mm) Length of stented segment (mm)
Overlapping SES Overlapping PES p (n ⫽ 55, (n ⫽ 59, Value 104 lesions) 105 lesions) 0 47 (45.2%)
0 35 (33.3%)
— 0.08
18 (17.3%)
18 (17.1%)
0.97
39 (37.5%) 0 43 (41.3%) 41 (39.4%) 17 (16.3%) 3 (2.9%) 6 (5.8%) 19 (18.3%) 3.0 ⫾ 0.3 53.8 ⫾ 15.8
52 (49.5%) 0 37 (35.2%) 52 (49.5%) 15 (14.3%) 0 9 (8.6%) 23 (21.9%) 3.0 ⫾ 0.3 48.7 ⫾ 15.6
0.08 — 0.36 0.14 0.68 0.10 0.43 0.51 1.0 0.10
were pretreated with 325 mg of aspirin orally before PCI. Clopidogrel 300 to 600 mg was also preloaded before PCI, followed by daily administration of 75 mg, and patients were instructed to continue this regimen for ⱖ6 months. During PCI, patients received anticoagulation with bivalirudin (a bolus of 0.75 mg/kg, followed by an intravenous infusion of 1.75 mg/kg/hour) or unfractionated heparin (a bolus of 40 U/kg and additional heparin to achieve an activated clotting time of 250 to 300 seconds). Activated clotting time was routinely measured (Hemochron, International Technidyne Corporation, Edison, New Jersey) before and during PCI. Platelet glycoprotein IIb/IIIa inhibitors were administered at the operators’ discretion. All patients routinely underwent pre- and postintervention 12-lead electrocardiography. Creatine kinase-MB enzyme assays were routinely obtained from blood samples before PCI and after intervention. Measurements were repeated every 8 hours until a peak value was reached and values began returning to normal (4 mg/dl in our laboratory). Q-wave myocardial infarction was defined as the presence of new pathologic Q waves on electrocardiogram associated with an increase in creatine kinase-MB ⱖ2 times the upper normal value. Non– Q-wave myocardial infarction was defined as an increase
in creatine kinase-MB ⱖ2 times the upper normal value without new Q waves. Target lesion revascularization was defined as a repeat revascularization within the stent or in the 5-mm distal or proximal segments adjacent to the stent. Target vessel revascularization was defined as revascularization driven by any lesion located in the same previously treated epicardial vessel. Major adverse cardiac events were defined as a combination of death, Q-wave myocardial infarction, and target lesion revascularization or target vessel revascularization. Angiographic success was defined as a final residual stenosis ⬍30% with Thrombolysis In Myocardial Infarction grade ⱖ3 flow. Lesion type (A, B1, B2, or C) was defined according to a modified classification of the American College of Cardiology/American Heart Association.11 Stent thrombosis was defined as an occlusion or filling defect at the stent site documented by angiography and was categorized as subacute (from the end of the procedure to 30 days) or late (⬎30 days). Baseline procedural information and in-hospital outcomes were recorded and entered into the database. Patients were contacted after PCI by trained quality assurance nurses who worked exclusively with the database to determine clinical events after PCI. Clinical follow-ups were performed by telephone contact, mailed questionnaire, or office visit at 30 days and 6 months. A committee independently adjudicated all subsequent clinical events. All clinical follow-ups were available in the overlapping SES group, and 95% of clinical follow-ups were available in the overlapping PES group. All statistical analysis was performed with SAS 8.2 (SAS Institute, Cary, North Carolina). Continuous variables were expressed as mean ⫾ SD and categorical data as percentages. Student’s t test was used to compare continuous variables, and chi-square statistics or Fisher’s exact test was used to compare categorical values. A p value ⬍0.05 was considered statistically significant. Baseline clinical and angiographic characteristics of overlapping SES and PES groups are listed in Tables 1 and 2. Baseline clinical characteristics were balanced between the 2 study groups. Angiographic and procedural characteristics were also matched between groups. In-hospital complications and 30-day and 6-month clinical outcomes are presented in Table 3. In-hospital complications were similar between groups. There were no deaths or Q-wave myocardial infarctions in either group. At 30-day follow-up, death, Q-wave myocardial infarction, non–Q-wave myocardial infarction, and major adverse cardiac events were similar between groups. There was no subacute thrombosis in either group. At 6-month follow-up, these clinical outcomes were similar between groups, as were target lesion and target vessel revascularizations. There was no late thrombosis in either group (Table 3). Kaplan-Meier event-free survival curves are shown in Figure 1. The 2 curves display the percentage of event-free survival over time after stent placement in the 2 study groups. Survival rate was similar between groups (p ⫽ 0.71).
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Table 3 Clinical outcomes of the study population Variable In-hospital complications Angiographic success Dissection Death Q-wave myocardial infarction Non–Q-wave myocardial infarction 30-Day outcomes (no. of patients) Target lesion revascularization/MACEs Target vessel revascularization/MACEs Death Q-wave myocardial infarction Non–Q-wave myocardial infarction Subacute thrombosis 6-Month outcomes (no. of patients) Target lesion revascularization/MACEs Target vessel revascularization/MACEs Death Q-wave myocardial infarction Non–Q-wave myocardial infarction Target lesion revascularization Target vessel revascularization Late thrombosis
Overlapping SES (n ⫽ 55, 104 lesions)
Overlapping PES (n ⫽ 59, 105 lesions)
p Value
97 (93.3%) 3 (2.9%) 0 0 13 (23.6%) 55 1 (1.8%) 1 (1.8%) 0 1 (1.8%) 3 (5.5%) 0 55 5 (9.1%) 5 (9.1%) 2 (3.6%) 1 (1.8%) 3 (5.5%) 3 (5.5%) 3 (5.5%) 0
99 (94.3%) 1 (1.0%) 0 0 7 (11.9%) 59 0 (0.0%) 0 1 (1.7%) 0 2 (3.4%) 0 56 3 (5.4%) 4 (7.1%) 2 (3.6%) 1 (1.8%) 2 (3.6%) 1 (1.8%) 2 (3.6%) 0
0.76 0.31 — — 0.10 0.30 0.30 0.99 0.30 0.59 — 0.45 0.71 0.99 0.99 0.63 0.30 0.63 —
MACE ⫽ major adverse cardiac events.
Figure 1. Kaplan-Meier event-free survival curves of the overlapping SES and PES groups over time after stent placement.
Discussion The present study demonstrates that implantation of overlapping drug-eluting stents for treatment of long, native coronary lesions is feasible and effective but associated with an increase in non–Q-wave myocardial infarction rates. Clinical outcomes appeared similar in patients treated with overlapping SES implantation compared with those treated with overlapping PES implantation. In the bare metal stent era, long stent implantations for treatment of long coronary lesions were associated with poor outcomes secondary to high restenotic rates and high rates of repeat revascularization. In addition, the idea of whether overlapping stent implantation has worse outcomes compared with single-stent implantation has been contro-
versial. Lee et al2 studied 32 patients treated with 1 long stent and 32 patients treated with 2 overlapping stents. In-stent restenotic rate at 6 months was very high in the 2 groups (39% vs 41%), but there was no significant difference between the 2 groups. Kastrati et al1 also showed that lesion length was a significant independent risk factor for restenosis; however, in their study, overlapping stenting was found to be an independent risk factor for restenosis. However, in the contemporary drug-eluting stent era, Degertekin et al12 demonstrated that overlapping SES implantation is safe and effective for very long coronary lesions. In their study, they used ⱖ2 overlapping stents at a minimum length of 41 mm to treat native coronary lesions. Their target lesion revascularization, target vessel revascularization, and major adverse cardiac event rates were compatible with ours. Further, there have been concerns that the risk for thrombosis may increase after implantation of the long stent. In the study by Degertekin et al,12 no documented thrombotic stent occlusion was observed. Our findings are consistent with those results; there was no subacute or late thrombosis in our patients who received overlapping drug-eluting stents. Taxus V,10 a substudy of patients who received overlapping Taxus stents, showed a higher rate of periprocedural myocardial necrosis compared with control patients. The explanation of this phenomenon is that patients treated with overlapping Taxus stents had higher incidences of side branch compromise with decreased flow after overlapping stent placement. Previously we reported that, in overlapping SES versus nonoverlapping SES,13 in-hospital complications were similar among study groups, except for non–Qwave myocardial infarction, which was significantly higher in the overlapping SES group than in the nonoverlapping
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SES group (23.6% vs 7.7%, p ⫽ 0.04). This higher rate of myocardial necrosis was due to periprocedural side branch compromises, including side branch narrowing, occlusion, and decreased flow. In the present study, although there was no statistical significance, numerically in-hospital non–Qwave myocardial infarction was lower in the overlapping PES group than in the overlapping SES group (11.9% vs 23.6%, p ⫽ 0.10). This phenomenon could be explained by branch occlusion, narrowing, and decreased Thrombolysis In Myocardial Infarction flow, which were lower in the overlapping PES group than in the overlapping SES group based on side branch analysis. Another explanation for the increase in non–Q-wave myocardial infarction in the 2 groups could be related to overall plaque burden of diffuse disease and some distal embolization. A future comparison of shorter overlapping stents versus longer stents can examine this hypothesis. An additional explanation could simply be the play of chance. The present study is limited due to its retrospective nature, its nonrandomized analysis, its limited sample size, and its lack of systematic angiographic follow-up. Nevertheless, it confirms that, despite an increase in non–Q-wave myocardial infarction, the efficacy and safety of overlapping stents can be obtained when diffuse lesions in human coronary arteries are treated regardless of type of drugeluting stent. 1. Kastrati A, Elezi S, Dirschinger J, Hadamitzky M, Neumann FJ, Schomig A. Influence of lesion length on restenosis after coronary stent placement. Am J Cardiol 1999;83:1617–1622. 2. Lee SH, Jang Y, Oh SJ, Park KJ, Moon YS, Min JW, Yang JY, Jang GJ. Overlapping vs. one long stenting in long coronary lesions. Catheter Cardiovasc Interv 2004;62:298 –302. 3. Morice MC, Serruys PW, Sousa JE, Fajadet J, Ban Hayashi E, Perin M, Colombo A, Schuler G, Barragan P, Guagliumi G, et al. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med 2002;346:1773–1780. 4. Moses JW, Leon MB, Popma JJ, Fitzgerald PJ, Holmes DR, O’Shaughnessy C, Caputo RP, Kereiakes DJ, Williams DO, Teirstein
5.
6.
7.
8.
9.
10.
11.
12.
13.
PS, 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. Grube E, Silber S, Hauptmann KE, Mueller R, Buellesfeld L, Gerckens U, Russell ME. TAXUS I: six- and twelve-month results from a randomized, double-blind trial on a slow-release paclitaxel-eluting stent for de novo coronary lesions. Circulation 2003;107:38 – 42. Colombo A, Drzewiecki J, Banning A, Grube E, Hauptmann K, Silber S, Dudek D, Fort S, Schiele F, Zmudka K, et al. Randomized study to assess the effectiveness of slow- and moderate-release polymer-based paclitaxel-eluting stents for coronary artery lesions. Circulation 2003; 108:788 –794. Stone GW, Ellis SG, Cox DA, Hermiller J, O’Shaughnessy C, Mann JT, Turco M, Caputo R, Bergin P, Greenberg J, et al. A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease. N Engl J Med 2004;350:221–231. Morice M-C, Colombo A, Meier B, Serruys P, Tamburino C, Guagliumi G, Sousa E, Stoll H-P. Sirolimus- vs paclitaxel-eluting stents in de novo coronary artery lesions: the REALITY trial. JAMA 2006;295: 895–904. Windecker S, Remondino A, Eberli FR, Jüni P, Räber L, Wenaweser P, Togni M, Billinger M, Tüller D, Seiler C, et al. Sirolimus-eluting and paclitaxel-eluting stents for coronary revascularization. N Engl J Med 2005;353:653– 662. Stone GW, Ellis SG, O’Shaughnessy, et al, for the TAXUS V ISR Investigators. Paclitaxel-eluting stents versus vascular brachytherapy for in-stent restenosis within bare-metal stents: the TAXUS V ISR randomized trial. JAMA 2006;295:1253–1263. Ryan TJ, Faxon DP, Gunnar RM, Kennedy JW, King SB III, Loop FD, Peterson KL, Reeves TJ, Williams DO, Winters WL. Guidelines for percutaneous transluminal coronary angioplasty: a report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Subcommittee on Percutaneous Transluminal Coronary Angioplasty). Circulation 1988;78:486 –502. Degertekin M, Arampatzis CA, Lemos PA, Saia F, Hoye A, Daemen J, Tanabe K, Lee CH, Hofma SJ, Sianos G, et al. Very long sirolimuseluting stent implantation for de novo coronary lesions. Am J Cardiol 2004;93:826 – 829. Chu WW, Kuchulakanti PK, Torguson R, Wang B, Clavijo LC, Suddath WO, Pichard AD, Satler LF, Kent KM, Waksman R. Clinical outcomes of overlapping versus nonoverlapping sirolimus-eluting stents in patients undergoing percutaneous coronary intervention. Catheter Cardiovasc Interv 2006;67:595–599.
Division of Cardiology, Washington Hospital Center, Washington, DC. Manuscript received May 4, 2006; revised manuscript received and accepted July 3, 2006. *Corresponding author: Tel: 202-877-8575; fax: 202-877-2715. E-mail address: [email protected] (R. Waksman). 0002-9149/06/$ – see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2006.07.032
Paclitaxel-eluting Stents for Coronary Revascularization (SIRTAX) Study,9 a 1,012-patient trial, showed favorable results in the SES arm in terms of target lesion revascularization, late lumen loss, and binary restenosis. Data on overlapping PESs for long lesions in the Taxus V study were alarming. It showed an increase in creatine kinase and myonecrosis in the Taxus stent compared with the bare metal stent.10 Limited information is available on overlapping SESs for diffuse lesions, and a comparison of overlapping SESs versus PESs in treating long lesions is not available. To further pursue this interesting subject, we conducted this retrospective analysis to compare the clinical outcomes of overlapping SES and PES implantation. Methods and Results We retrospectively analyzed patients who underwent percutaneous coronary intervention (PCI) with SESs (Cypher, Johnson & Johnson Cordis Corp., Miami, Florida) and PESs (Taxus, Boston Scientific Corp., Natick, Massachusetts) at Washington Hospital Center (Washington, DC). Since approval of SESs and PESs by the Food and Drug Administration, 114 patients who underwent overlapping drug-eluting stent implantation for native coronary lesions were identified, 55 (104 lesions) of whom received overlapping SES implantation with ⬎1-mm overlap (overlapping SES group) and 59 (105 lesions) received overlapping PES implantation with ⬎1-mm overlap (overlapping PES group). In the 2 study groups, patients who presented with acute myocardial infarction and cardiogenic shock were excluded. Coronary angioplasty was performed according to standard percutaneous techniques using the femoral approach and standard techniques for stent implantation. All patients www.AJConline.org
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Table 1 Baseline clinical characteristics of the study population Variable
Overlapping SES (n ⫽ 55)
Overlapping PES (n ⫽ 59)
p Value
Age (yrs) Men Diabetes mellitus Systemic hypertension Hyperlipidemia Chronic renal insufficiency Smoker Ejection fraction
62.9 ⫾ 12.3 41 (74.5%) 24 (43.6%) 46 (83.6%) 48 (87.3%) 5 (9.1%) 6 (10.9%) 0.52 ⫾ 0.13
66.3 ⫾ 11.0 38 (64.4%) 18 (30.5%) 46 (78.0%) 48 (81.4%) 8 (13.6%) 9 (15.3%) 0.49 ⫾ 0.14
0.16 0.24 0.15 0.44 0.39 0.45 0.49 0.21
Table 2 Angiographic and procedural characteristics of the study population Variable
Left main coronary artery Left anterior descending coronary artery Left circumflex coronary artery Right coronary artery Saphenous vein graft Proximal lesion Mid-lesion Distal lesion Ostial lesion Restenotic lesion Type C lesion Stent diameter (mm) Length of stented segment (mm)
Overlapping SES Overlapping PES p (n ⫽ 55, (n ⫽ 59, Value 104 lesions) 105 lesions) 0 47 (45.2%)
0 35 (33.3%)
— 0.08
18 (17.3%)
18 (17.1%)
0.97
39 (37.5%) 0 43 (41.3%) 41 (39.4%) 17 (16.3%) 3 (2.9%) 6 (5.8%) 19 (18.3%) 3.0 ⫾ 0.3 53.8 ⫾ 15.8
52 (49.5%) 0 37 (35.2%) 52 (49.5%) 15 (14.3%) 0 9 (8.6%) 23 (21.9%) 3.0 ⫾ 0.3 48.7 ⫾ 15.6
0.08 — 0.36 0.14 0.68 0.10 0.43 0.51 1.0 0.10
were pretreated with 325 mg of aspirin orally before PCI. Clopidogrel 300 to 600 mg was also preloaded before PCI, followed by daily administration of 75 mg, and patients were instructed to continue this regimen for ⱖ6 months. During PCI, patients received anticoagulation with bivalirudin (a bolus of 0.75 mg/kg, followed by an intravenous infusion of 1.75 mg/kg/hour) or unfractionated heparin (a bolus of 40 U/kg and additional heparin to achieve an activated clotting time of 250 to 300 seconds). Activated clotting time was routinely measured (Hemochron, International Technidyne Corporation, Edison, New Jersey) before and during PCI. Platelet glycoprotein IIb/IIIa inhibitors were administered at the operators’ discretion. All patients routinely underwent pre- and postintervention 12-lead electrocardiography. Creatine kinase-MB enzyme assays were routinely obtained from blood samples before PCI and after intervention. Measurements were repeated every 8 hours until a peak value was reached and values began returning to normal (4 mg/dl in our laboratory). Q-wave myocardial infarction was defined as the presence of new pathologic Q waves on electrocardiogram associated with an increase in creatine kinase-MB ⱖ2 times the upper normal value. Non– Q-wave myocardial infarction was defined as an increase
in creatine kinase-MB ⱖ2 times the upper normal value without new Q waves. Target lesion revascularization was defined as a repeat revascularization within the stent or in the 5-mm distal or proximal segments adjacent to the stent. Target vessel revascularization was defined as revascularization driven by any lesion located in the same previously treated epicardial vessel. Major adverse cardiac events were defined as a combination of death, Q-wave myocardial infarction, and target lesion revascularization or target vessel revascularization. Angiographic success was defined as a final residual stenosis ⬍30% with Thrombolysis In Myocardial Infarction grade ⱖ3 flow. Lesion type (A, B1, B2, or C) was defined according to a modified classification of the American College of Cardiology/American Heart Association.11 Stent thrombosis was defined as an occlusion or filling defect at the stent site documented by angiography and was categorized as subacute (from the end of the procedure to 30 days) or late (⬎30 days). Baseline procedural information and in-hospital outcomes were recorded and entered into the database. Patients were contacted after PCI by trained quality assurance nurses who worked exclusively with the database to determine clinical events after PCI. Clinical follow-ups were performed by telephone contact, mailed questionnaire, or office visit at 30 days and 6 months. A committee independently adjudicated all subsequent clinical events. All clinical follow-ups were available in the overlapping SES group, and 95% of clinical follow-ups were available in the overlapping PES group. All statistical analysis was performed with SAS 8.2 (SAS Institute, Cary, North Carolina). Continuous variables were expressed as mean ⫾ SD and categorical data as percentages. Student’s t test was used to compare continuous variables, and chi-square statistics or Fisher’s exact test was used to compare categorical values. A p value ⬍0.05 was considered statistically significant. Baseline clinical and angiographic characteristics of overlapping SES and PES groups are listed in Tables 1 and 2. Baseline clinical characteristics were balanced between the 2 study groups. Angiographic and procedural characteristics were also matched between groups. In-hospital complications and 30-day and 6-month clinical outcomes are presented in Table 3. In-hospital complications were similar between groups. There were no deaths or Q-wave myocardial infarctions in either group. At 30-day follow-up, death, Q-wave myocardial infarction, non–Q-wave myocardial infarction, and major adverse cardiac events were similar between groups. There was no subacute thrombosis in either group. At 6-month follow-up, these clinical outcomes were similar between groups, as were target lesion and target vessel revascularizations. There was no late thrombosis in either group (Table 3). Kaplan-Meier event-free survival curves are shown in Figure 1. The 2 curves display the percentage of event-free survival over time after stent placement in the 2 study groups. Survival rate was similar between groups (p ⫽ 0.71).
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Table 3 Clinical outcomes of the study population Variable In-hospital complications Angiographic success Dissection Death Q-wave myocardial infarction Non–Q-wave myocardial infarction 30-Day outcomes (no. of patients) Target lesion revascularization/MACEs Target vessel revascularization/MACEs Death Q-wave myocardial infarction Non–Q-wave myocardial infarction Subacute thrombosis 6-Month outcomes (no. of patients) Target lesion revascularization/MACEs Target vessel revascularization/MACEs Death Q-wave myocardial infarction Non–Q-wave myocardial infarction Target lesion revascularization Target vessel revascularization Late thrombosis
Overlapping SES (n ⫽ 55, 104 lesions)
Overlapping PES (n ⫽ 59, 105 lesions)
p Value
97 (93.3%) 3 (2.9%) 0 0 13 (23.6%) 55 1 (1.8%) 1 (1.8%) 0 1 (1.8%) 3 (5.5%) 0 55 5 (9.1%) 5 (9.1%) 2 (3.6%) 1 (1.8%) 3 (5.5%) 3 (5.5%) 3 (5.5%) 0
99 (94.3%) 1 (1.0%) 0 0 7 (11.9%) 59 0 (0.0%) 0 1 (1.7%) 0 2 (3.4%) 0 56 3 (5.4%) 4 (7.1%) 2 (3.6%) 1 (1.8%) 2 (3.6%) 1 (1.8%) 2 (3.6%) 0
0.76 0.31 — — 0.10 0.30 0.30 0.99 0.30 0.59 — 0.45 0.71 0.99 0.99 0.63 0.30 0.63 —
MACE ⫽ major adverse cardiac events.
Figure 1. Kaplan-Meier event-free survival curves of the overlapping SES and PES groups over time after stent placement.
Discussion The present study demonstrates that implantation of overlapping drug-eluting stents for treatment of long, native coronary lesions is feasible and effective but associated with an increase in non–Q-wave myocardial infarction rates. Clinical outcomes appeared similar in patients treated with overlapping SES implantation compared with those treated with overlapping PES implantation. In the bare metal stent era, long stent implantations for treatment of long coronary lesions were associated with poor outcomes secondary to high restenotic rates and high rates of repeat revascularization. In addition, the idea of whether overlapping stent implantation has worse outcomes compared with single-stent implantation has been contro-
versial. Lee et al2 studied 32 patients treated with 1 long stent and 32 patients treated with 2 overlapping stents. In-stent restenotic rate at 6 months was very high in the 2 groups (39% vs 41%), but there was no significant difference between the 2 groups. Kastrati et al1 also showed that lesion length was a significant independent risk factor for restenosis; however, in their study, overlapping stenting was found to be an independent risk factor for restenosis. However, in the contemporary drug-eluting stent era, Degertekin et al12 demonstrated that overlapping SES implantation is safe and effective for very long coronary lesions. In their study, they used ⱖ2 overlapping stents at a minimum length of 41 mm to treat native coronary lesions. Their target lesion revascularization, target vessel revascularization, and major adverse cardiac event rates were compatible with ours. Further, there have been concerns that the risk for thrombosis may increase after implantation of the long stent. In the study by Degertekin et al,12 no documented thrombotic stent occlusion was observed. Our findings are consistent with those results; there was no subacute or late thrombosis in our patients who received overlapping drug-eluting stents. Taxus V,10 a substudy of patients who received overlapping Taxus stents, showed a higher rate of periprocedural myocardial necrosis compared with control patients. The explanation of this phenomenon is that patients treated with overlapping Taxus stents had higher incidences of side branch compromise with decreased flow after overlapping stent placement. Previously we reported that, in overlapping SES versus nonoverlapping SES,13 in-hospital complications were similar among study groups, except for non–Qwave myocardial infarction, which was significantly higher in the overlapping SES group than in the nonoverlapping
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SES group (23.6% vs 7.7%, p ⫽ 0.04). This higher rate of myocardial necrosis was due to periprocedural side branch compromises, including side branch narrowing, occlusion, and decreased flow. In the present study, although there was no statistical significance, numerically in-hospital non–Qwave myocardial infarction was lower in the overlapping PES group than in the overlapping SES group (11.9% vs 23.6%, p ⫽ 0.10). This phenomenon could be explained by branch occlusion, narrowing, and decreased Thrombolysis In Myocardial Infarction flow, which were lower in the overlapping PES group than in the overlapping SES group based on side branch analysis. Another explanation for the increase in non–Q-wave myocardial infarction in the 2 groups could be related to overall plaque burden of diffuse disease and some distal embolization. A future comparison of shorter overlapping stents versus longer stents can examine this hypothesis. An additional explanation could simply be the play of chance. The present study is limited due to its retrospective nature, its nonrandomized analysis, its limited sample size, and its lack of systematic angiographic follow-up. Nevertheless, it confirms that, despite an increase in non–Q-wave myocardial infarction, the efficacy and safety of overlapping stents can be obtained when diffuse lesions in human coronary arteries are treated regardless of type of drugeluting stent. 1. Kastrati A, Elezi S, Dirschinger J, Hadamitzky M, Neumann FJ, Schomig A. Influence of lesion length on restenosis after coronary stent placement. Am J Cardiol 1999;83:1617–1622. 2. Lee SH, Jang Y, Oh SJ, Park KJ, Moon YS, Min JW, Yang JY, Jang GJ. Overlapping vs. one long stenting in long coronary lesions. Catheter Cardiovasc Interv 2004;62:298 –302. 3. Morice MC, Serruys PW, Sousa JE, Fajadet J, Ban Hayashi E, Perin M, Colombo A, Schuler G, Barragan P, Guagliumi G, et al. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med 2002;346:1773–1780. 4. Moses JW, Leon MB, Popma JJ, Fitzgerald PJ, Holmes DR, O’Shaughnessy C, Caputo RP, Kereiakes DJ, Williams DO, Teirstein
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