International Journal of Cardiology 179 (2015) 385–389
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International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Long term outcomes in octogenarians undergoing percutaneous coronary intervention: Comparison of bare metal versus drug eluting stent☆ Shanmugam Uthamalingam a,⁎, Imad Ahmado b, Vijairam Selvaraj c, Robert Dewey d, James Flynn d a
Division of Cardiology, Baystate Medical Center, Springfield, MA, United States Division of Cardiology, Michigan State University, East Lansing, MI, United States c Department of Internal Medicine, Baystate Medical Center, Springfield, MA, United States d New England Heart Institute, Catholic Medical Center, Manchester, NH, United States b
a r t i c l e
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Article history: Received 19 May 2014 Received in revised form 26 October 2014 Accepted 3 November 2014 Available online 5 November 2014 Keywords: Octogenarians Elderly Stent Coronary syndrome
a b s t r a c t Background: Octogenarians have been under-represented in percutaneous coronary intervention (PCI) trials, thus making difficult to choose the best type of stent in this patient population. We compared the outcomes of drug eluting (DES) and bare metal stent (BMS) at one year after implantation in this special population. Methods: A total of 320 consecutive patients over 80 years undergoing PCI with BMS (n = 218) or DES (n = 102) were retrospectively studied. One year major adverse cardiac events (MACEs) defined as cardiac death, non-fatal myocardial infarction and target vessel revascularization (TVR) were compared between the two groups. Cox regression analysis was used for data analysis. Results: The one year incidence of MACE was higher in the BMS group (18.8% vs 9.8%, adjusted hazard ratio [HR] 2.33; 95% confidence interval [C.I.]: 1.12 to 4.86 p = 0.02). Diabetes mellitus was an independent predictor for increased MACE (adjusted HR: 1.99; C.I. 1.06 to 3.77, p = 0.03). One year incidence of TVR was higher in the BMS group (10.0% vs 3.9% adjusted HR: 2.94; C.I. 1.01 to 8.59 p = 0.045). There was no difference in cardiac death between the two groups. Conclusion: During one year follow-up, octogenarians treated with BMS had an increased risk of MACE compared with those treated with DES. DES should be preferred in indications recognized from current PCI guidelines. © 2014 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Octogenarian patients are increasingly growing population among the elderly with increasing proportion of them undergoing percutaneous coronary intervention (PCI) for coronary artery revascularization. PCI is being increasingly considered as the preferred method for coronary artery revascularization in octogenarians because this special population is considered high risk due to multiple co-morbid medical illnesses and associated complex coronary lesions [1]. Major prospective revascularization trials have excluded this high-risk population thus making it difficult to determine the best strategy of stent selection in this patient population [2,3]. Currently, patients greater than 80 years of age are treated with either drug or bare metal stents (BMS) based on the discretion of the operator who performs the procedure and such selection depends upon the stent availability (size and length), type and location of the lesion
☆ List of support/grant information: None. ⁎ Corresponding author. E-mail address: [email protected] (S. Uthamalingam).
http://dx.doi.org/10.1016/j.ijcard.2014.11.012 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
(proximal or distal part of the diseased vessel), co-morbidity like diabetes and duration of anti-platelet therapy with its associated bleeding complications in this frail population. Despite higher costs of the drug eluting stent (DES) and the lack of evidence of its benefit in preventing death and recurrent myocardial infarction in octogenarians, there is increasing tendency to use DES as the stent of choice by interventional cardiologists [1]. There have been no randomized controlled trials conducted to explore these treatment options among this population, long-term clinical outcomes including the safety profile between these two stent types. The purpose of our study was to evaluate in-hospital and one-year clinical outcomes of octogenarian patients undergoing PCI in a ‘real world’ situation and to observe whether there were differences between BMS and DES groups of patients in regard to their efficacy and safety. 2. Methods All consecutive octogenarian patients who underwent PCI at New England Heart Institute at Catholic Medical Center, a major participant of Northern New England Cardiovascular disease registry, in Manchester, New Hampshire and received either at least one BMS (January 2000 till March 2008) or DES (April 2003 till March 2008) were included in the study. The study population (n = 320) was divided into two groups: BMS group
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(n = 218) and DES group (n = 102). Patients who received both BMS and DES during their PCI were excluded from the study. Baseline demographic, clinical characteristics and angiographic data of all patients who underwent PCI were prospectively entered into a database by a dedicated team of well-trained data collection specialists in our hospital who also maintained the data. All patients were followed up to one-year. The institutional review board at Catholic Medical Center approved the study. All PCI procedures were performed following the current standard guidelines at the time of the procedure [4]. All patients were treated with aspirin and clopidogrel. Clopidogrel was maintained for ≥1 month in patients treated with BMS and ≥6 months treated with DES. Anticoagulation during PCI was accomplished with unfractionated heparin or low molecular weight heparin according to the standard protocol. The use of glycoprotein IIb/IIIa inhibitors was at the discretion of the interventional cardiologist performing the procedure. Complete procedural success was defined as residual stenosis b50% stenosis as estimated by the TIMI (thrombosis in myocardial infarction) grade 3 flow in the intervened lesions. The patients were followed till the time of discharge in the hospital and for one year following that for the primary end point of major adverse cardiac events (MACEs) defined as one or combination of the following events: cardiac death, non-fatal myocardial infarction (MI) and target vessel revascularization (TVR). Secondary end points included all cause mortality, components of MACE, the incidence of target lesion revascularization (TLR), hemorrhagic complications (major and minor) and stent thrombosis. Myocardial infarction was based on the current American College of Cardiology (ACC) guidelines [5] : rise and gradual fall of troponin or more rapid rise and fall of CK-MB associated with or without ST elevation or development of pathological Q wave in the electrocardiogram. TVR was defined as repeat revascularization within the treated vessel by PCI or surgical bypass of any segment of the target vessel [6]. TLR was defined as any repeat percutaneous intervention or bypass surgery of the target vessel performed for restenosis or other complications of the target lesion [6]. Stent thrombosis (ST) was defined as an acute coronary syndrome with angiographic documentation of thrombus within or adjacent to a previously successfully stented vessel and divided based on the timing of event according to the Academic Research Consortium criteria [6] as follows: Acute (≤24 h after implantation), Sub-acute (b30 days after implantation) and late (30 days to one year). Major bleeding complications were defined according to the criteria used in the TIMI IIb study: any retroperitoneal, intracranial or intraocular hemorrhage and bleeding resulting in death; fall in hemoglobin ≥ 3 g/dL or at least 2 units of blood transfused [7]. Minor bleeding complications were considered clinically important bleeding event, which did not meet the criteria for the major bleeding ones (for example: epistaxis or extensive bruising).
3. Statistical analysis Categorical variables are described as percentages and compared using chi-square test or Fisher exact test as appropriate. Continuous variables were described as mean ± SD and compared using independent sample t test or the Wilcoxon sum test as appropriate. Analysis of independent predictors of clinical endpoints was performed with univariate and multivariate Cox proportional hazards regression analysis. The variables included into the multivariate analysis are age, gender, diabetes mellitus, hypertension, smoking, hyperlipidemia, renal failure, prior myocardial infarction, coronary artery bypass graft (CABG) surgery, left ventricular ejection fraction, indication for PCI, use of glycoprotein IIb/IIIa inhibitors, complete procedural success, treatment of left main coronary artery, ACC type of lesion and variables that were significant on univariable analysis. Final results were described as adjusted hazard ratio (HR adjusted) with 95% confidence interval (C.I.). A p value of ≤0.05 was considered statistically significant. All statistical analyses were performed using SPSS 17 (PASW 17) statistical software (SPSS, Inc., Chicago, Illinois). 4. Results 4.1. Clinical and angiographic characteristics Baseline clinical characteristics of the patient belonging to the two groups are described in Table 1. Patients belonged to the BMS group had a higher incidence of prior CABG (10.1% vs 3.9; p = 0.04) and depressed LVEF% (48.5 ± 12.3 vs 51.6 ± 10.8; p = 0.03) compared to DES group. Analyzing the initial clinical presentation for PCI, patients in the BMS group had decreased incidence of unstable angina (27.5% vs 40.2%; p = 0.03) and increased incidence of both ST elevation and non-ST elevation myocardial infarctions (50.9% vs 32.4%; p = 0.002) compared to DES group. There were no differences in other clinical comorbidities and cardiac risk factors between the two groups of patients.
Table 1 Baseline characteristics of patients belonging to BMS and DES stent groups. Variables
BMS (N = 218)
DES (N = 102)
p value
Age (years) Female Hypertension Hyperlipidemia Prior heart failure Smoking Diabetes mellitus Renal impairment Prior myocardial infarction History of prior CABG History of prior PCI Family history of CAD COPD LVEF % History of PVD
83.6 ± 2.7 51.4% (112) 74.8% (163) 57.3% (125) 13.3% (29) 5.5% (12) 21.6% (47) 8.2% (19) 11.0% (24) 10.1% (22) 3.2% (7) 11.5% (25) 17.4% (38) 48.5 ± 12.3 36.2% (79)
83.6 ± 2.5 44.1% (45) 76.5% (78) 67.6% (69) 18.6% (19) 3.9% (4) 27.5% (28) 7.8% (8) 14.7% (15) 3.9% (4) 5.9% (6) 13.7% (14) 20.6% (21) 51.6 ± 10.8 41.2% (42)
0.73 0.23 0.78 0.11 0.24 0.78 0.26 0.56 0.63 0.04 0.36 0.59 0.54 0.03 0.06
Clinical presentation Stable angina Unstable angina NSTEMI/STEMI Cardiogenic shock
16.1% (35) 27.5% (60) 50.9% (111) 0.5% (1)
16.7% (17) 40.2% (41) 32.4% (33) 0.9% (1)
0.87 0.03 0.002 0.53
Values are expressed as mean ± SD or percent. CAD = coronary artery disease, COPD = chronic obstructive Pulmonary disease, LVEF = left ventricular ejection fraction, NSTEMI = non-ST elevation myocardial infarction. STEMI = ST elevation myocardial infarction.
Baseline angiographic details describing the lesion and procedural characteristics are outlined in Table 2. The treated lesion type and intervened coronary artery territory were similar in both groups of patients. Patients in the BMS group who received single stent to treat their diseased lesions were lesser in number compared to the DES group (41.3% vs 69.6%; p = 0.001). There were no differences in complete procedural success between BMS and DES patient groups (95.9% vs 99.0%).
Table 2 Angiographic and procedural characteristics. Variable Number of diseased vessels [% (n)] 1 2 ≥3 Number of treated vessels Coronary vessel treated [%(n)] Right Left anterior descending Left circumflex Left main coronary Number of lesions treated Lesion length Lesion type A B1 B2 C Stent number 1 2 ≥3 Stent length (in mm) Collaterals Thrombus present Complete procedural success Complications Dissection Perforation Distal embolization Glycoprotein IIa/IIIb inhibitor use
BMS (N = 218)
DES (N = 102)
p value
64.7% (141) 25.7% (56) 9.2% (20) 1.4 ± 0.7
59.8% (61) 32.4% (33) 7.8% (8) 1.5 ± 0.6
0.46 0.23 0.83 0.58
44.0% (96) 56.4% (123) 38.9% (85) 5.0% (11) 1.3 ± 0.6 21.2 ± 12
48.0% (49) 58.8% (60) 38.2% (39) 3.9% (4) 1.3 ± 0.6 24.6 ± 10.8
0.55 0.72 0.92 0.78 0.15 0.25
6.9% (15) 32.1% (70) 36.7% (80) 29.8% (65)
10.8% (11) 29.4% (30) 33.3% (34) 37.3% (38)
0.27 0.69 0.62 0.20
41.3% (90) 44.5% (97) 13.8% (30) 24.3 ± 10.2 2.3% (5) 21.0% (42) 95.9% (208)
69.6% (71) 20.6% (21) 9.8% (10) 38.2 ± 18.6 4.9% (5) 11.8% (12) 99.0% (101)
.001 .001 0.37 0.09 0.29 0.22 0.18
1.4% (3) 0.0 (0) 0.5% (1) 43.1% (94)
1.9% (2) 0.0 (0) 0.0 (0) 39.2% (40)
0.62 – 0.62 0.18
Values are expressed as mean ± SD or percent.
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Table 3 In-hospital and one year outcomes. Variable
In-hospital outcome
All cause death Cardiac death Non-fatal MI TLR TVR CABG Total MACE Major bleeding Minor bleeding
One year outcome
BMS (n = 218)
DES (n = 102)
p value
BMS (n = 218)
DES (n = 102)
p value
2.8% (6) 2.8% (6) 0.9% (2) 0.0 0.0 0.0 3.6% (8) 2.8% (6) 2.2% (5)
1.9% (2) 1.9% (2) 0.9% (1) 0.0 0.0 0.0 2.9% (3) 2.9% (3) 1.9% (2)
0.5 0.5 0.7 – – – 0.4 0.6 0.4
6.8% (15) 5.9% (13) 2.7% (6) 3.6% (8) 10.1% (22) 3.6% (8) 18.8% (41) 5.0% (11) 6.4% (14)
3.9% (4) 2.9% (3) 2.9% (3) 3.9% (4) 3.9% (4) 0.0 (0) 9.8% (10) 4.9% (5) 5.8% (6)
0.3 0.2 0.6 0.6 0.03 0.4 0.03 0.8 0.9
MI = myocardial infarction, TLR = target lesion revascularization, TVR = target vessel revascularization, CABG = coronary artery bypass graft, MACE = major adverse cardiovascular events, BMS = bare metal stent, DES = drug eluting stent.
4.2. In hospital outcomes
5. Discussion
The in-hospital outcomes are described in Table 3. There was no statistically significant difference observed regarding in-hospital composite MACE between the BMS and DES groups. There were no TLR, TVR or CABG performed in either group. Though the incidence of minor bleeding was observed to be higher in the BMS group compared to the DES group, the incidence of major bleeding complications was similar and both remained insignificant.
Our study represents one of the largest single center registries of octogenarians treated with PCI in the stent era. The main finding of our study was significantly lower adjusted risk of cumulative MACE outcomes at one year follow-up after DES implantation comparing BMS. The differences in target vessel revascularization remained significant after adjustment for multiple variables between BMS and DES; with no differences in all cause mortality, TLR, stent thrombosis or hemorrhagic complications, thus making both BMS and DES to have comparable safety and efficacy. Also, there were no significant differences in the in-hospital outcomes in terms of MACE, non-fatal MI and hemorrhagic complications. Randomized clinical trials [8–10] have traditionally excluded patients more than 80 years of age making comparison between BMS and DES being difficult in this patient population and hence results of our present study would be not be comparable with current data in the literature; however similarities to studies comparing the outcomes between these two stent types could be analyzed. Majority of the studies [8,11,12] comparing the BMS and DES have examined the rate of target lesion revascularization or restenosis as the primary end point with results showing effective reduction in the restenosis rate with DES compared to BMS. Also, only few studies [13–17] have compared the occurrence of the MACE, particularly myocardial infarction and all cause mortality between BMS and DES. In a meta analysis, Roiron et al. [15] showed the reduction of MACE (death, MI, and revascularization) at
4.3. One-year clinical outcomes One year clinical outcomes are outlined in Table 3. At one year, the incidence of cumulative MACE (18.8% vs 9.8%; p = 0.03) and TVR (10.1% vs 3.9%; p = 0.03) was higher in the BMS group compared to DES group. However the frequency of all cause mortality (6.8% vs 3.9%; p = 0.3), cardiac death (5.9% vs 2.9%; p = 0.2), non-fatal myocardial infarction (2.7% vs 2.9%; p = 0.6) and TLR (3.6% vs 3.9%; p = 0.6) was similar between the two groups. Incidence of major and minor bleedings was not significant between the two groups of patients. The incidence of stent thrombosis was compared between the BMS and DES groups of patients depending upon the time of occurrence of stent thrombosis after the index procedure and is detailed in Table 4. There were no comparable differences in stent thrombosis between BMS and DES groups across all the time range. Cumulative incidence of MACE and independent predictors of cumulative MACE between the BMS and DES groups of patients are shown in Fig. 1 and Table 5 respectively. The use of BMS was an independent predictor of increased MACE at one year (HR adjusted: 2.33; 95% confidence interval [C.I.]: 1.12 to 4.86; p = 0.02). Cumulative incidence of TVR between the BMS and DES groups of patients is shown in Fig. 2. One year incidence of TVR was higher in the BMS group (10.1% vs 3.9% HRadjusted: 2.94; C.I. 1.01 to 8.59; p = 0.045). Independent predictors of TVR at one year were diabetes mellitus (HRadjusted; 2.92; 95% C.I.: 1.28 to 6.66; p = 0.01) and number of stents implanted (HRadjusted: 1.52; 95% C.I.: 1.18 to 2.02; p = 0.03).
Table 4 Incidence of stent thrombosis according to the time of occurrence after index PCI procedure. Stent thrombosis
BMS (n = 218)
DES (n = 102)
p value
Acute Sub acute Late Total
0.5% (1) 0.9% (2) 0.5% (1) 1.8% (4)
0.0 (0) 0.9% (1) 1.9% (2) 2.9% (3)
0.4 0.9 0.2 0.6
BMS = bare metal stent, DES = drug eluting stent.
Fig. 1. One year cumulative event rate for major adverse cardiovascular events between bare metal stent and drug groups.
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Table 5 Independent predictors of one year major adverse cardiovascular events. Variable
Adjusted hazard ratio
95% confidence interval
p value
Bare metal stent Diabetes mellitus Type C lesion Complete procedural success
2.33 1.99 1.58 0.24
1.12–4.86 1.06–3.77 1.39–1.88 0.09–0.59
0.02 0.03 0.01 0.002
9 months with DES group compared to BMS with no differences when analyzed individually in all cause mortality, myocardial infarction and stent thrombosis between the two groups similar to results observed in our study. Applegate et al. [18], who compared the frequency of TVR and myocardial infarction at 9 months after the index PCI procedure showed significant reduction in TVR among the DES group compared to BMS with no differences in MI. Although TVR rate at one year in our study was more in the BMS group, all cause death and MI at one year remained similar in both DES and BMS groups. Current study results reflective of Applegate et al. [18] may possibly due to comparable complex angiographic lesions, and differences in antiplatelet therapy between the two study groups, with need for prolonged duration of the dual antiplatelet agent in DES group compared to BMS. Groeneveld et al. [16] compared the MACE outcomes (defined as all cause mortality, MI and revascularization rate) and components of MACE between BMS and DES in a large group of medicare population and showed significant reduction in MACE outcomes and all individual components of MACE in DES group at 1 and 2 years. Though, the results of MACE outcomes were similar to our study, the study was lacking angiographic and procedure details and not adjusted for all the potential angiographic variables in this patient population with complex coronary lesions. In our study, diabetes was an independent predictor of MACE outcomes and TVR. Recent long term follow-up study [19] showed that there were no significant differences between BMS and DES diabetic patient groups in terms of their composite outcome of death and myocardial infarction with a median 2.5 years of follow-up. However in the same study population, diabetic patients who received DES had a decreased rate of restenosis compared to BMS. Additional information about the optimal treatment of elderly diabetic patients including octogenarians undergoing PCI with either BMS or DES could be derived from the results of future randomized trials. Comparison of the in-hospital and long term safety profile in terms of stent thrombosis and hemorrhagic complications among octogenarians
Fig. 2. One year cumulative event rate for target vessel revascularization between bare metal stent and drug eluting stent groups.
between the BMS and DES groups remained similar as demonstrated by our study. Though the absence of differences in stent thrombosis and bleeding complications between the two groups may be partly explained by the limited number of events, it is comparable to and remained similar to other randomized studies [20–23]. This study is single center and retrospective with its inherent limitations. The relatively small study population with limited number of in-hospital outcomes to detect significant association between DES and BMS may preclude drawing any definitive conclusions on safety outcomes between these two stent types in this special population. However, the number of octogenarian patients undergoing PCI is lesser in number in any single center and hence our study reflects comparison of DES and BMS in a real world experience among this special patient population. Our study encourages the use of DES in octogenarians undergoing PCI according to the current recognized indications which will facilitate lesser frequency of revascularization and combined major adverse cardiovascular outcomes, thus making age as a less discriminating factor in the type of stent selection. Multicenter prospective randomized controlled clinical trials comparing BMS and DES in the octogenarians undergoing PCI are needed in the future to better delineate the risk of bleeding and safety outcomes. Conflict of interest The authors report no relationships that could be construed as a conflict of interest. Acknowledgment The authors acknowledge the invaluable assistance of Cynthia David, MLS MPS and Revathi Hariram B.S. References [1] S.H. McKellar, M.L. Brown, R.L. Frye, H.V. Schaff, T.M. Sundt III, Comparison of coronary revascularization procedures in octogenarians: a systematic review and metaanalysis, Nat. Clin. Pract. Cardiovasc. Med. 5 (2008) 738–746. [2] P.Y. Lee, K.P. Alexander, B.G. Hammill, S.K. Pasquali, E.D. Peterson, Representation of elderly persons and women in published randomized trials of acute coronary syndromes, JAMA 286 (2001) 708–713. [3] M. Hordijk-Trion, M. Lenzen, W. Wijns, P. de Jaegere, M.L. Simoons, W.J. Scholte op Reimer, M.E. Bertrand, N. Mercado, E. Boersma, EHS-CR Investigators, Patients enrolled in coronary intervention trials are not representative of patients in clinical practice: results from the Euro Heart Survey on Coronary Revascularization, Eur. Heart J. 27 (2006) 671–678. [4] R.J. Applegate, M.A. Grabarczyk, W.C. Little, T. Craven, M. Walkup, F.R. Kahl, G.A. Braden, K.M. Rankin, M.A. Kutcher, Vascular closure devices in patients treated with anticoagulation and IIb/IIIa receptor inhibitors during percutaneous revascularization, J. Am. Coll. Cardiol. 40 (2002) 78–83. [5] J.S. Alpert, K. Thygesen, E. Antman, J.P. Bassand, Myocardial infarction redefined—a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction, J. Am. Coll. Cardiol. 36 (2000) 959–969. [6] D.E. Cutlip, S. Windecker, R. Mehran, A. Boam, D.J. Cohen, G.A. van Es, P.G. Steg, M.A. Morel, L. Mauri, P. Vranckx, E. McFadden, A. Lansky, M. Hamon, M.W. Krucoff, P.W. Serruys, Academic Research Consortium, Clinical end points in coronary stent trials: a case for standardized definitions, Circulation 115 (2007) 2344–2351. [7] E.M. Antman, C.H. McCabe, E.P. Gurfinkel, A.G. Turpie, P.J. Bernink, D. Salein, A. Bayes De Luna, K. Fox, J.M. Lablanche, D. Radley, J. Premmereur, E. Braunwald, Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q-wave myocardial infarction. Results of the thrombolysis in myocardial infarction (TIMI) 11B trial, Circulation 100 (1999) 1593–1601. [8] G.W. Stone, S.G. Ellis, L. Cannon, J.T. Mann, J.D. Greenberg, D. Spriggs, C.D. O'Shaughnessy, S. DeMaio, P. Hall, J.J. Popma, J. Koglin, M.E. Russell, TAXUS V Investigators, Comparison of a polymer-based paclitaxel-eluting stent with a bare metal stent in patients with complex coronary artery disease: a randomized controlled trial, JAMA 294 (2005) 1215–1223. [9] J.W. Moses, M.B. Leon, J.J. Popma, P.J. Fitzgerald, D.R. Holmes, C. O'Shaughnessy, R.P. Caputo, D.J. Kereiakes, D.O. Williams, P.S. Teirstein, J.L. Jaeger, R.E. Kuntz, SIRIUS Investigators, Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery, N. Engl. J. Med. 349 (2003) 1315–1323. [10] M.C. Morice, P.W. Serruys, J.E. Sousa, J. Fajadet, E. Ban Hayashi, M. Perin, A. Colombo, G. Schuler, P. Barragan, G. Guagliumi, F. Molnàr, R. Falotico, RAVEL Study Group, Randomized study with the sirolimus-coated Bx velocity balloon-expandable stent in the treatment of patients with de novo native coronary artery lesions. A
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Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Long term outcomes in octogenarians undergoing percutaneous coronary intervention: Comparison of bare metal versus drug eluting stent☆ Shanmugam Uthamalingam a,⁎, Imad Ahmado b, Vijairam Selvaraj c, Robert Dewey d, James Flynn d a
Division of Cardiology, Baystate Medical Center, Springfield, MA, United States Division of Cardiology, Michigan State University, East Lansing, MI, United States c Department of Internal Medicine, Baystate Medical Center, Springfield, MA, United States d New England Heart Institute, Catholic Medical Center, Manchester, NH, United States b
a r t i c l e
i n f o
Article history: Received 19 May 2014 Received in revised form 26 October 2014 Accepted 3 November 2014 Available online 5 November 2014 Keywords: Octogenarians Elderly Stent Coronary syndrome
a b s t r a c t Background: Octogenarians have been under-represented in percutaneous coronary intervention (PCI) trials, thus making difficult to choose the best type of stent in this patient population. We compared the outcomes of drug eluting (DES) and bare metal stent (BMS) at one year after implantation in this special population. Methods: A total of 320 consecutive patients over 80 years undergoing PCI with BMS (n = 218) or DES (n = 102) were retrospectively studied. One year major adverse cardiac events (MACEs) defined as cardiac death, non-fatal myocardial infarction and target vessel revascularization (TVR) were compared between the two groups. Cox regression analysis was used for data analysis. Results: The one year incidence of MACE was higher in the BMS group (18.8% vs 9.8%, adjusted hazard ratio [HR] 2.33; 95% confidence interval [C.I.]: 1.12 to 4.86 p = 0.02). Diabetes mellitus was an independent predictor for increased MACE (adjusted HR: 1.99; C.I. 1.06 to 3.77, p = 0.03). One year incidence of TVR was higher in the BMS group (10.0% vs 3.9% adjusted HR: 2.94; C.I. 1.01 to 8.59 p = 0.045). There was no difference in cardiac death between the two groups. Conclusion: During one year follow-up, octogenarians treated with BMS had an increased risk of MACE compared with those treated with DES. DES should be preferred in indications recognized from current PCI guidelines. © 2014 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Octogenarian patients are increasingly growing population among the elderly with increasing proportion of them undergoing percutaneous coronary intervention (PCI) for coronary artery revascularization. PCI is being increasingly considered as the preferred method for coronary artery revascularization in octogenarians because this special population is considered high risk due to multiple co-morbid medical illnesses and associated complex coronary lesions [1]. Major prospective revascularization trials have excluded this high-risk population thus making it difficult to determine the best strategy of stent selection in this patient population [2,3]. Currently, patients greater than 80 years of age are treated with either drug or bare metal stents (BMS) based on the discretion of the operator who performs the procedure and such selection depends upon the stent availability (size and length), type and location of the lesion
☆ List of support/grant information: None. ⁎ Corresponding author. E-mail address: [email protected] (S. Uthamalingam).
http://dx.doi.org/10.1016/j.ijcard.2014.11.012 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
(proximal or distal part of the diseased vessel), co-morbidity like diabetes and duration of anti-platelet therapy with its associated bleeding complications in this frail population. Despite higher costs of the drug eluting stent (DES) and the lack of evidence of its benefit in preventing death and recurrent myocardial infarction in octogenarians, there is increasing tendency to use DES as the stent of choice by interventional cardiologists [1]. There have been no randomized controlled trials conducted to explore these treatment options among this population, long-term clinical outcomes including the safety profile between these two stent types. The purpose of our study was to evaluate in-hospital and one-year clinical outcomes of octogenarian patients undergoing PCI in a ‘real world’ situation and to observe whether there were differences between BMS and DES groups of patients in regard to their efficacy and safety. 2. Methods All consecutive octogenarian patients who underwent PCI at New England Heart Institute at Catholic Medical Center, a major participant of Northern New England Cardiovascular disease registry, in Manchester, New Hampshire and received either at least one BMS (January 2000 till March 2008) or DES (April 2003 till March 2008) were included in the study. The study population (n = 320) was divided into two groups: BMS group
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(n = 218) and DES group (n = 102). Patients who received both BMS and DES during their PCI were excluded from the study. Baseline demographic, clinical characteristics and angiographic data of all patients who underwent PCI were prospectively entered into a database by a dedicated team of well-trained data collection specialists in our hospital who also maintained the data. All patients were followed up to one-year. The institutional review board at Catholic Medical Center approved the study. All PCI procedures were performed following the current standard guidelines at the time of the procedure [4]. All patients were treated with aspirin and clopidogrel. Clopidogrel was maintained for ≥1 month in patients treated with BMS and ≥6 months treated with DES. Anticoagulation during PCI was accomplished with unfractionated heparin or low molecular weight heparin according to the standard protocol. The use of glycoprotein IIb/IIIa inhibitors was at the discretion of the interventional cardiologist performing the procedure. Complete procedural success was defined as residual stenosis b50% stenosis as estimated by the TIMI (thrombosis in myocardial infarction) grade 3 flow in the intervened lesions. The patients were followed till the time of discharge in the hospital and for one year following that for the primary end point of major adverse cardiac events (MACEs) defined as one or combination of the following events: cardiac death, non-fatal myocardial infarction (MI) and target vessel revascularization (TVR). Secondary end points included all cause mortality, components of MACE, the incidence of target lesion revascularization (TLR), hemorrhagic complications (major and minor) and stent thrombosis. Myocardial infarction was based on the current American College of Cardiology (ACC) guidelines [5] : rise and gradual fall of troponin or more rapid rise and fall of CK-MB associated with or without ST elevation or development of pathological Q wave in the electrocardiogram. TVR was defined as repeat revascularization within the treated vessel by PCI or surgical bypass of any segment of the target vessel [6]. TLR was defined as any repeat percutaneous intervention or bypass surgery of the target vessel performed for restenosis or other complications of the target lesion [6]. Stent thrombosis (ST) was defined as an acute coronary syndrome with angiographic documentation of thrombus within or adjacent to a previously successfully stented vessel and divided based on the timing of event according to the Academic Research Consortium criteria [6] as follows: Acute (≤24 h after implantation), Sub-acute (b30 days after implantation) and late (30 days to one year). Major bleeding complications were defined according to the criteria used in the TIMI IIb study: any retroperitoneal, intracranial or intraocular hemorrhage and bleeding resulting in death; fall in hemoglobin ≥ 3 g/dL or at least 2 units of blood transfused [7]. Minor bleeding complications were considered clinically important bleeding event, which did not meet the criteria for the major bleeding ones (for example: epistaxis or extensive bruising).
3. Statistical analysis Categorical variables are described as percentages and compared using chi-square test or Fisher exact test as appropriate. Continuous variables were described as mean ± SD and compared using independent sample t test or the Wilcoxon sum test as appropriate. Analysis of independent predictors of clinical endpoints was performed with univariate and multivariate Cox proportional hazards regression analysis. The variables included into the multivariate analysis are age, gender, diabetes mellitus, hypertension, smoking, hyperlipidemia, renal failure, prior myocardial infarction, coronary artery bypass graft (CABG) surgery, left ventricular ejection fraction, indication for PCI, use of glycoprotein IIb/IIIa inhibitors, complete procedural success, treatment of left main coronary artery, ACC type of lesion and variables that were significant on univariable analysis. Final results were described as adjusted hazard ratio (HR adjusted) with 95% confidence interval (C.I.). A p value of ≤0.05 was considered statistically significant. All statistical analyses were performed using SPSS 17 (PASW 17) statistical software (SPSS, Inc., Chicago, Illinois). 4. Results 4.1. Clinical and angiographic characteristics Baseline clinical characteristics of the patient belonging to the two groups are described in Table 1. Patients belonged to the BMS group had a higher incidence of prior CABG (10.1% vs 3.9; p = 0.04) and depressed LVEF% (48.5 ± 12.3 vs 51.6 ± 10.8; p = 0.03) compared to DES group. Analyzing the initial clinical presentation for PCI, patients in the BMS group had decreased incidence of unstable angina (27.5% vs 40.2%; p = 0.03) and increased incidence of both ST elevation and non-ST elevation myocardial infarctions (50.9% vs 32.4%; p = 0.002) compared to DES group. There were no differences in other clinical comorbidities and cardiac risk factors between the two groups of patients.
Table 1 Baseline characteristics of patients belonging to BMS and DES stent groups. Variables
BMS (N = 218)
DES (N = 102)
p value
Age (years) Female Hypertension Hyperlipidemia Prior heart failure Smoking Diabetes mellitus Renal impairment Prior myocardial infarction History of prior CABG History of prior PCI Family history of CAD COPD LVEF % History of PVD
83.6 ± 2.7 51.4% (112) 74.8% (163) 57.3% (125) 13.3% (29) 5.5% (12) 21.6% (47) 8.2% (19) 11.0% (24) 10.1% (22) 3.2% (7) 11.5% (25) 17.4% (38) 48.5 ± 12.3 36.2% (79)
83.6 ± 2.5 44.1% (45) 76.5% (78) 67.6% (69) 18.6% (19) 3.9% (4) 27.5% (28) 7.8% (8) 14.7% (15) 3.9% (4) 5.9% (6) 13.7% (14) 20.6% (21) 51.6 ± 10.8 41.2% (42)
0.73 0.23 0.78 0.11 0.24 0.78 0.26 0.56 0.63 0.04 0.36 0.59 0.54 0.03 0.06
Clinical presentation Stable angina Unstable angina NSTEMI/STEMI Cardiogenic shock
16.1% (35) 27.5% (60) 50.9% (111) 0.5% (1)
16.7% (17) 40.2% (41) 32.4% (33) 0.9% (1)
0.87 0.03 0.002 0.53
Values are expressed as mean ± SD or percent. CAD = coronary artery disease, COPD = chronic obstructive Pulmonary disease, LVEF = left ventricular ejection fraction, NSTEMI = non-ST elevation myocardial infarction. STEMI = ST elevation myocardial infarction.
Baseline angiographic details describing the lesion and procedural characteristics are outlined in Table 2. The treated lesion type and intervened coronary artery territory were similar in both groups of patients. Patients in the BMS group who received single stent to treat their diseased lesions were lesser in number compared to the DES group (41.3% vs 69.6%; p = 0.001). There were no differences in complete procedural success between BMS and DES patient groups (95.9% vs 99.0%).
Table 2 Angiographic and procedural characteristics. Variable Number of diseased vessels [% (n)] 1 2 ≥3 Number of treated vessels Coronary vessel treated [%(n)] Right Left anterior descending Left circumflex Left main coronary Number of lesions treated Lesion length Lesion type A B1 B2 C Stent number 1 2 ≥3 Stent length (in mm) Collaterals Thrombus present Complete procedural success Complications Dissection Perforation Distal embolization Glycoprotein IIa/IIIb inhibitor use
BMS (N = 218)
DES (N = 102)
p value
64.7% (141) 25.7% (56) 9.2% (20) 1.4 ± 0.7
59.8% (61) 32.4% (33) 7.8% (8) 1.5 ± 0.6
0.46 0.23 0.83 0.58
44.0% (96) 56.4% (123) 38.9% (85) 5.0% (11) 1.3 ± 0.6 21.2 ± 12
48.0% (49) 58.8% (60) 38.2% (39) 3.9% (4) 1.3 ± 0.6 24.6 ± 10.8
0.55 0.72 0.92 0.78 0.15 0.25
6.9% (15) 32.1% (70) 36.7% (80) 29.8% (65)
10.8% (11) 29.4% (30) 33.3% (34) 37.3% (38)
0.27 0.69 0.62 0.20
41.3% (90) 44.5% (97) 13.8% (30) 24.3 ± 10.2 2.3% (5) 21.0% (42) 95.9% (208)
69.6% (71) 20.6% (21) 9.8% (10) 38.2 ± 18.6 4.9% (5) 11.8% (12) 99.0% (101)
.001 .001 0.37 0.09 0.29 0.22 0.18
1.4% (3) 0.0 (0) 0.5% (1) 43.1% (94)
1.9% (2) 0.0 (0) 0.0 (0) 39.2% (40)
0.62 – 0.62 0.18
Values are expressed as mean ± SD or percent.
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Table 3 In-hospital and one year outcomes. Variable
In-hospital outcome
All cause death Cardiac death Non-fatal MI TLR TVR CABG Total MACE Major bleeding Minor bleeding
One year outcome
BMS (n = 218)
DES (n = 102)
p value
BMS (n = 218)
DES (n = 102)
p value
2.8% (6) 2.8% (6) 0.9% (2) 0.0 0.0 0.0 3.6% (8) 2.8% (6) 2.2% (5)
1.9% (2) 1.9% (2) 0.9% (1) 0.0 0.0 0.0 2.9% (3) 2.9% (3) 1.9% (2)
0.5 0.5 0.7 – – – 0.4 0.6 0.4
6.8% (15) 5.9% (13) 2.7% (6) 3.6% (8) 10.1% (22) 3.6% (8) 18.8% (41) 5.0% (11) 6.4% (14)
3.9% (4) 2.9% (3) 2.9% (3) 3.9% (4) 3.9% (4) 0.0 (0) 9.8% (10) 4.9% (5) 5.8% (6)
0.3 0.2 0.6 0.6 0.03 0.4 0.03 0.8 0.9
MI = myocardial infarction, TLR = target lesion revascularization, TVR = target vessel revascularization, CABG = coronary artery bypass graft, MACE = major adverse cardiovascular events, BMS = bare metal stent, DES = drug eluting stent.
4.2. In hospital outcomes
5. Discussion
The in-hospital outcomes are described in Table 3. There was no statistically significant difference observed regarding in-hospital composite MACE between the BMS and DES groups. There were no TLR, TVR or CABG performed in either group. Though the incidence of minor bleeding was observed to be higher in the BMS group compared to the DES group, the incidence of major bleeding complications was similar and both remained insignificant.
Our study represents one of the largest single center registries of octogenarians treated with PCI in the stent era. The main finding of our study was significantly lower adjusted risk of cumulative MACE outcomes at one year follow-up after DES implantation comparing BMS. The differences in target vessel revascularization remained significant after adjustment for multiple variables between BMS and DES; with no differences in all cause mortality, TLR, stent thrombosis or hemorrhagic complications, thus making both BMS and DES to have comparable safety and efficacy. Also, there were no significant differences in the in-hospital outcomes in terms of MACE, non-fatal MI and hemorrhagic complications. Randomized clinical trials [8–10] have traditionally excluded patients more than 80 years of age making comparison between BMS and DES being difficult in this patient population and hence results of our present study would be not be comparable with current data in the literature; however similarities to studies comparing the outcomes between these two stent types could be analyzed. Majority of the studies [8,11,12] comparing the BMS and DES have examined the rate of target lesion revascularization or restenosis as the primary end point with results showing effective reduction in the restenosis rate with DES compared to BMS. Also, only few studies [13–17] have compared the occurrence of the MACE, particularly myocardial infarction and all cause mortality between BMS and DES. In a meta analysis, Roiron et al. [15] showed the reduction of MACE (death, MI, and revascularization) at
4.3. One-year clinical outcomes One year clinical outcomes are outlined in Table 3. At one year, the incidence of cumulative MACE (18.8% vs 9.8%; p = 0.03) and TVR (10.1% vs 3.9%; p = 0.03) was higher in the BMS group compared to DES group. However the frequency of all cause mortality (6.8% vs 3.9%; p = 0.3), cardiac death (5.9% vs 2.9%; p = 0.2), non-fatal myocardial infarction (2.7% vs 2.9%; p = 0.6) and TLR (3.6% vs 3.9%; p = 0.6) was similar between the two groups. Incidence of major and minor bleedings was not significant between the two groups of patients. The incidence of stent thrombosis was compared between the BMS and DES groups of patients depending upon the time of occurrence of stent thrombosis after the index procedure and is detailed in Table 4. There were no comparable differences in stent thrombosis between BMS and DES groups across all the time range. Cumulative incidence of MACE and independent predictors of cumulative MACE between the BMS and DES groups of patients are shown in Fig. 1 and Table 5 respectively. The use of BMS was an independent predictor of increased MACE at one year (HR adjusted: 2.33; 95% confidence interval [C.I.]: 1.12 to 4.86; p = 0.02). Cumulative incidence of TVR between the BMS and DES groups of patients is shown in Fig. 2. One year incidence of TVR was higher in the BMS group (10.1% vs 3.9% HRadjusted: 2.94; C.I. 1.01 to 8.59; p = 0.045). Independent predictors of TVR at one year were diabetes mellitus (HRadjusted; 2.92; 95% C.I.: 1.28 to 6.66; p = 0.01) and number of stents implanted (HRadjusted: 1.52; 95% C.I.: 1.18 to 2.02; p = 0.03).
Table 4 Incidence of stent thrombosis according to the time of occurrence after index PCI procedure. Stent thrombosis
BMS (n = 218)
DES (n = 102)
p value
Acute Sub acute Late Total
0.5% (1) 0.9% (2) 0.5% (1) 1.8% (4)
0.0 (0) 0.9% (1) 1.9% (2) 2.9% (3)
0.4 0.9 0.2 0.6
BMS = bare metal stent, DES = drug eluting stent.
Fig. 1. One year cumulative event rate for major adverse cardiovascular events between bare metal stent and drug groups.
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Table 5 Independent predictors of one year major adverse cardiovascular events. Variable
Adjusted hazard ratio
95% confidence interval
p value
Bare metal stent Diabetes mellitus Type C lesion Complete procedural success
2.33 1.99 1.58 0.24
1.12–4.86 1.06–3.77 1.39–1.88 0.09–0.59
0.02 0.03 0.01 0.002
9 months with DES group compared to BMS with no differences when analyzed individually in all cause mortality, myocardial infarction and stent thrombosis between the two groups similar to results observed in our study. Applegate et al. [18], who compared the frequency of TVR and myocardial infarction at 9 months after the index PCI procedure showed significant reduction in TVR among the DES group compared to BMS with no differences in MI. Although TVR rate at one year in our study was more in the BMS group, all cause death and MI at one year remained similar in both DES and BMS groups. Current study results reflective of Applegate et al. [18] may possibly due to comparable complex angiographic lesions, and differences in antiplatelet therapy between the two study groups, with need for prolonged duration of the dual antiplatelet agent in DES group compared to BMS. Groeneveld et al. [16] compared the MACE outcomes (defined as all cause mortality, MI and revascularization rate) and components of MACE between BMS and DES in a large group of medicare population and showed significant reduction in MACE outcomes and all individual components of MACE in DES group at 1 and 2 years. Though, the results of MACE outcomes were similar to our study, the study was lacking angiographic and procedure details and not adjusted for all the potential angiographic variables in this patient population with complex coronary lesions. In our study, diabetes was an independent predictor of MACE outcomes and TVR. Recent long term follow-up study [19] showed that there were no significant differences between BMS and DES diabetic patient groups in terms of their composite outcome of death and myocardial infarction with a median 2.5 years of follow-up. However in the same study population, diabetic patients who received DES had a decreased rate of restenosis compared to BMS. Additional information about the optimal treatment of elderly diabetic patients including octogenarians undergoing PCI with either BMS or DES could be derived from the results of future randomized trials. Comparison of the in-hospital and long term safety profile in terms of stent thrombosis and hemorrhagic complications among octogenarians
Fig. 2. One year cumulative event rate for target vessel revascularization between bare metal stent and drug eluting stent groups.
between the BMS and DES groups remained similar as demonstrated by our study. Though the absence of differences in stent thrombosis and bleeding complications between the two groups may be partly explained by the limited number of events, it is comparable to and remained similar to other randomized studies [20–23]. This study is single center and retrospective with its inherent limitations. The relatively small study population with limited number of in-hospital outcomes to detect significant association between DES and BMS may preclude drawing any definitive conclusions on safety outcomes between these two stent types in this special population. However, the number of octogenarian patients undergoing PCI is lesser in number in any single center and hence our study reflects comparison of DES and BMS in a real world experience among this special patient population. Our study encourages the use of DES in octogenarians undergoing PCI according to the current recognized indications which will facilitate lesser frequency of revascularization and combined major adverse cardiovascular outcomes, thus making age as a less discriminating factor in the type of stent selection. Multicenter prospective randomized controlled clinical trials comparing BMS and DES in the octogenarians undergoing PCI are needed in the future to better delineate the risk of bleeding and safety outcomes. Conflict of interest The authors report no relationships that could be construed as a conflict of interest. Acknowledgment The authors acknowledge the invaluable assistance of Cynthia David, MLS MPS and Revathi Hariram B.S. References [1] S.H. McKellar, M.L. Brown, R.L. Frye, H.V. Schaff, T.M. Sundt III, Comparison of coronary revascularization procedures in octogenarians: a systematic review and metaanalysis, Nat. Clin. Pract. Cardiovasc. Med. 5 (2008) 738–746. [2] P.Y. Lee, K.P. Alexander, B.G. Hammill, S.K. Pasquali, E.D. Peterson, Representation of elderly persons and women in published randomized trials of acute coronary syndromes, JAMA 286 (2001) 708–713. [3] M. Hordijk-Trion, M. Lenzen, W. Wijns, P. de Jaegere, M.L. Simoons, W.J. Scholte op Reimer, M.E. Bertrand, N. Mercado, E. Boersma, EHS-CR Investigators, Patients enrolled in coronary intervention trials are not representative of patients in clinical practice: results from the Euro Heart Survey on Coronary Revascularization, Eur. Heart J. 27 (2006) 671–678. [4] R.J. Applegate, M.A. Grabarczyk, W.C. Little, T. Craven, M. Walkup, F.R. Kahl, G.A. Braden, K.M. Rankin, M.A. Kutcher, Vascular closure devices in patients treated with anticoagulation and IIb/IIIa receptor inhibitors during percutaneous revascularization, J. Am. Coll. Cardiol. 40 (2002) 78–83. [5] J.S. Alpert, K. Thygesen, E. Antman, J.P. Bassand, Myocardial infarction redefined—a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction, J. Am. Coll. Cardiol. 36 (2000) 959–969. [6] D.E. Cutlip, S. Windecker, R. Mehran, A. Boam, D.J. Cohen, G.A. van Es, P.G. Steg, M.A. Morel, L. Mauri, P. Vranckx, E. McFadden, A. Lansky, M. Hamon, M.W. Krucoff, P.W. Serruys, Academic Research Consortium, Clinical end points in coronary stent trials: a case for standardized definitions, Circulation 115 (2007) 2344–2351. [7] E.M. Antman, C.H. McCabe, E.P. Gurfinkel, A.G. Turpie, P.J. Bernink, D. Salein, A. Bayes De Luna, K. Fox, J.M. Lablanche, D. Radley, J. Premmereur, E. Braunwald, Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q-wave myocardial infarction. Results of the thrombolysis in myocardial infarction (TIMI) 11B trial, Circulation 100 (1999) 1593–1601. [8] G.W. Stone, S.G. Ellis, L. Cannon, J.T. Mann, J.D. Greenberg, D. Spriggs, C.D. O'Shaughnessy, S. DeMaio, P. Hall, J.J. Popma, J. Koglin, M.E. Russell, TAXUS V Investigators, Comparison of a polymer-based paclitaxel-eluting stent with a bare metal stent in patients with complex coronary artery disease: a randomized controlled trial, JAMA 294 (2005) 1215–1223. [9] J.W. Moses, M.B. Leon, J.J. Popma, P.J. Fitzgerald, D.R. Holmes, C. O'Shaughnessy, R.P. Caputo, D.J. Kereiakes, D.O. Williams, P.S. Teirstein, J.L. Jaeger, R.E. Kuntz, SIRIUS Investigators, Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery, N. Engl. J. Med. 349 (2003) 1315–1323. [10] M.C. Morice, P.W. Serruys, J.E. Sousa, J. Fajadet, E. Ban Hayashi, M. Perin, A. Colombo, G. Schuler, P. Barragan, G. Guagliumi, F. Molnàr, R. Falotico, RAVEL Study Group, Randomized study with the sirolimus-coated Bx velocity balloon-expandable stent in the treatment of patients with de novo native coronary artery lesions. A
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