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Prevalence and outcomes of intermediate saphenous vein graft lesions: Findings from the stenting of saphenous vein grafts randomized-controlled trial
International Journal of Cardiology 168 (2013) 2468–2473
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Prevalence and outcomes of intermediate saphenous vein graft lesions: Findings from the stenting of saphenous vein grafts randomized-controlled trial Abdul-rahman R. Abdel-karim a, b, Monica Da Silva a, b, Christopher Lichtenwalter c, James A. de Lemos a, b, Owen Obel a, b, Tayo Addo a, b, Michele Roesle a, Donald Haagen a, Bavana V. Rangan a, Lorenza Makke a, Omar M. Jeroudi a, b, Deepa Raghunathan a, b, Bilal Saeed d, Joseph K. Bissett e, Rajesh Sachdeva e, Vassilios V. Voudris f, Panagiotis Karyofillis f, Biswajit Kar g, James Rossen h, Panayotis Fasseas i, Peter Berger j, Subhash Banerjee a, b, Emmanouil S. Brilakis a, b,⁎ a
Veteran Affairs North Texas Healthcare System, Dallas, TX, USA University of Texas Southwestern Medical Center, Dallas, TX, USA The Cardiovascular and Arrhythmia Institute, Mesa, AZ, USA d Geisinger Medical Center, Danville, PA, USA e Central Arkansas Veterans Healthcare System and University of Arkansas for Medical Sciences, Little Rock, AR, USA f Onassis Cardiac Surgery Center, Athens, Greece g Michael E. DeBakey Veterans Affairs Medical Center, Houston TX, USA h Iowa City Veteran Affairs Medical Center, Iowa City, IA, USA i Medical College of Wisconsin, Milwaukee, WI, USA j Geisinger Clinic, Danville, PA, USA b c
a r t i c l e
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Article history: Received 28 November 2012 Accepted 9 March 2013 Available online 3 April 2013 Keywords: Saphenous vein grafts Percutaneous Coronary Interventions Stents
a b s t r a c t Background: We sought to examine the prevalence and progression rate of intermediate saphenous vein graft (SVG) lesions in the Stenting Of Saphenous vein grafts (SOS) trial. Methods: The baseline and follow-up angiograms of 80 patients participating in the SOS trial were analyzed to determine the prevalence of intermediate (30–60% angiographic diameter stenosis) SVG lesions and their progression rate. Results: At least one intermediate SVG lesion was present in 31 of 143 (22%) SVGs in 27 of 80 (34%) patients. Most intermediate lesions were present in the SOS stented SVGs (20 grafts in 19 patients). During a median follow-up of 35 months, angiographic follow-up was available for 28 grafts in 25 patients. Progression (defined as percent diameter stenosis ≥70% but b100% at follow-up angiography) was seen in 11 of 28 SVGs (39%) in 11 of 25 patients (44%). Progression rate at 12, 24 and 36 months was 28% and 47% and 84%, respectively. Seven of 11 patients (64%) with intermediate SVG lesion progression presented with an acute coronary syndrome and 8 (73%) underwent PCI. Four of the 28 grafts with intermediate lesions at baseline were 100% occluded at follow-up; all of those SVGs had received a stent in another location in the SVG as part of the SOS trial. Conclusions: Intermediate SVG lesions are common in patients undergoing SVG stenting, have high rates of progression and frequently present with an acute coronary syndrome. Further study of pharmacologic and mechanical treatments to prevent progression of these lesions is needed. Published by Elsevier Ireland Ltd.
1. Introduction In native coronary arteries intermediate stenoses have a favorable prognosis with low rates of rapid progression and lesion-related acute coronary syndromes [1,2]. In contrast, intermediate saphenous
Abbreviations: CABG, Coronary Artery Bypass Graft; HDL, High Density Lipoprotein; LDL, Low Density Lipoprotein; PCI, Percutaneous Coronary Intervention; SOS, Stenting Of Saphenous vein grafts trial; SVG, Saphenous Vein Graft. ⁎ Corresponding author at: Dallas VA Medical Center (111A), 4500 South Lancaster Road, Dallas, TX 75216, USA. Tel.: +1 214 857 1547; fax: +1 214 302 1341. E-mail address: [email protected] (E.S. Brilakis). 0167-5273/$ – see front matter. Published by Elsevier Ireland Ltd. http://dx.doi.org/10.1016/j.ijcard.2013.03.006
vein graft (SVG) lesions often progress rapidly [3–6], and have been associated with a two-fold increase in overall mortality independently of other comorbidities [4]. The VELETI (Moderate VEin Graft LEsion Stenting With the Taxus Stent and Intravascular Ultrasound) trial suggested that prophylactic stenting of intermediate SVG lesions with a paclitaxel-eluting stent (PES) may provide improved outcomes compared to medical therapy alone [6]. The Stenting Of Saphenous vein graft (SOS) trial (NCT00247208) randomized 80 patients with severe SVG lesions to PES or a similar bare metal stent (BMS) and demonstrated improved angiographic and clinical outcomes with PES [7–10]. An intriguing observation from SOS was that 2/3 of the target vessel revascularizations in
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PES-treated patients were due to progression of intermediate SVG lesions [7]. In the present study we sought to determine the prevalence and outcomes of intermediate SVG lesions in the SOS study population. 2. Methods 2.1. Patient population The design and primary results of the SOS trial have been published [7,10]. Briefly, the SOS was a multicenter, randomized, controlled trial that compared the clinical and angiographic outcomes after implantation of a PES vs. a similar BMS in SVG lesions. Patients were asked to return for follow-up angiography 12 months post stenting and were also followed clinically. Median clinical follow-up was 35 months. The author(s) of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.
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2.2. Angiographic analysis The baseline and follow-up angiograms were evaluated to determine whether an intermediate lesion (defined as 30–60% angiographic diameter stenosis by visual estimation, not considered to be responsible for the patient’s clinical presentation) was present and whether it progressed during follow-up. Assessment was performed blinded to the patient’s treatment allocation. Subsequently, quantitative angiographic analyses were performed using the CAAS automated edge detection system version 5.4. (Pie Medical Imaging, Maastricht, the Netherlands). The projection that best showed the stenosis in its tightest view was selected. Patients were considered to have had progression of the intermediate SVG lesion if it was found to have ≥70% but b100% angiographic diameter stenosis at follow-up. Patients with 100% occluded SVGs at follow-up were analyzed separately, because it was not possible to determine whether occlusion was due to progression of the intermediate SVG lesion or due to restenosis or thrombosis of the SOS-target SVG. If a patient had >1 intermediate lesion and at least one of those lesions progressed, he was considered to be a “progressor”.
Fig. 1. Prevalence and outcomes of patients (panel A) and saphenous vein grafts (panel B) with intermediate saphenous vein graft lesions. 1, two patients in this group had two saphenous vein grafts with intermediate lesions: in the first patient one saphenous vein graft progressed and one was occluded at follow-up and in the other patient one saphenous vein graft progressed and one saphenous vein graft did not progress. 2, two patients in this group had two saphenous vein grafts with intermediate lesions: in the first patient one saphenous vein graft did not progress and one was occluded at follow-up and in the other patient one saphenous vein graft did not progress and another saphenous vein graft was not injected at follow-up angiography.
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A.R. Abdel-karim et al. / International Journal of Cardiology 168 (2013) 2468–2473 Table 1 (continued)
Table 1 Baseline characteristics of the study population. Intermediate lesion No intermediate lesion P (patients = 53) (patients = 27) (SVGs = 112) (SVGs = 31) Age (years)a Men, n (%) Inpatient, n (%) Ethnicity, n (%) White Black Hispanic Years since coronary artery bypass graft surgerya Indication for PCI, n (%) Stable angina Unstable angina NSTEMI Other Hypertension, n (%) Hyperlipidemia, n (%) Diabetes mellitus, n (%) Current smoking, n (%) Prior myocardial infarction, n (%) Body mass index (kg/m2)a Statin at baseline, n (%) Ejection fraction, n (%) Not done ≥ 50% 40–49% 30–39% b30% Recipient vessel for all patent SVGs, n (%) LAD/Diagonal Circumflex/OM RCA/PDA Number of SVGs treated per patienta 1 2 Number of lesions treated per patienta SOS lesion location, n (%) Aortic anastomosis Proximal third Mid third Distal third Coronary anastomosis Recipient vessel for each SOS graft, n (%) LAD/Diagonal Circumflex/OM RCA/PDA Pre-stenting TIMI flow, n (%) 1 2 3 Post-stenting TIMI flow, n (%) 2 3 Embolic protection device use, n (%) Predilatation, n (%) Postdilatation, n (%) Maximum balloon diameter (mm)a Maximum inflation pressure (atm)a Contrast utilization (mL)a Fluoroscopy time (min)a Medications at the time of PCI Anticoagulation, n (%) Unfractionated heparin
71 ± 10 27 (100%) 21 (78%)
64 ± 8 53(100%) 35 (66%)
25 (93%) 1 (4%) 1 (4%) 12 ± 6
51 (96%) 1 (2%) 1 (2%) 11 ± 6
10 (37%) 6 (22%) 10 (37%) 1 (4%) 26 (96%) 24 (89%) 11 (41%) 7 (26%) 18 (67%)
15 (28.5%) 24 (45%) 8 (15%) 6 (11.5%) 49 (92.45%) 53 (100%) 21 (40%) 14 (26%) 28 (53%)
30 ± 4 23 (85%)
29 ± 4 48 (91%)
1 (3.5%) 18 (67%) 4 (15%) 3 (11%) 1 (3.5%)
6 (11%) 25 (47%) 14 (26.5%) 5 (9.5%) 3 (6%)
0.004a 1.0 0.28 0.78
0.56
Intermediate lesion No intermediate lesion P (patients = 53) (patients = 27) (SVGs = 112) (SVGs = 31) Bivalirudin Glycoprotein IIb/IIIa inhibitor, n (%) Post PCI myocardial infarction, n (%)
4 (15%) 3 (11%)
12 (23%) 6 (11%)
0.41 0.98
2/25 (8%)
2/40 (5%)
0.62
PCI, percutaneous coronary intervention; NSTEMI, non ST-segment elevation myocardial infarction; SVG, saphenous vein graft; LAD, left anterior descending artery; OM, obtuse marginal; RCA, right coronary artery; PDA, posterior descending artery; TIMI, thrombolysis in myocardial infarction. a mean ± standard deviation.
0.046 2.3. Statistical analysis
0.5 0.013 0.92 0.96 0.24
Continuous parameters were presented as mean ± standard deviation and were compared using the Wilcoxon rank-sum test. Nominal variables were presented as percentages and compared using the chi-square test. The incidence of intermediate SVG lesion progression was calculated using the Kaplan–Meier method. A p-value b0.05 was considered statistically significant for all analyses. Analyses were performed using JMP 8.0 (SAS Institute, Cary, North Carolina).
0.43 0.47 0.47
3. Results 3.1. Prevalence of intermediate SVG lesions
0.47 5 (16%) 13 (42%) 13 (42%) 1.15 ± 0.36
29 (26%) 46 (41%) 37 (33%) 1.07 ± 0.26
23 (85%) 4 (15%) 1.33 ± 0.62
49 (92%) 4 (8%) 1.43 ± 0.69
12 (33.3%) 7 (19.5%) 13 (36%) 1 (3%) 3 (8.3%)
18 (24%) 20 (26%) 22 (28%) 11 (15%) 5 (7%)
0.31
An intermediate SVG lesion was present in 31 of 143 (22%) patent SVGs in 27 of 80 (34%) SOS study patients (Fig. 1). The intermediate lesion
0.31 0.495 0.29
0.475 7 (23%) 11 (35%) 13 (42%)
18 (31.5%) 22 (38.5%) 17 (30%) 0.07
0 (0%) 8 (22%) 28 (78%)
4 (5%) 7 (9%) 65 (86%) 0.019
4 (11%) 32 (89%) 24 (67%)
1 (1%) 75 (99%) 36 (47%)
0.056
10 (28%) 11 (31%) 3.4 ± 0.5
25 (33%) 12 (16%) 3.1 ± 0.45
0.585 0.07 0.01
17.5 ± 2.4
16.5 ± 3.0
0.057
257 ± 84 21 ± 7
261 ± 109 20 ± 11
0.77 0.21
23 (85%)
42 (79%)
0.52
Fig. 2. Example of an intermediate saphenous vein graft lesion progression from baseline (panel A) to follow-up performed 15 months later (panel B).
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was present in a stented SVG in 20 grafts in 19 patients and in a non-stented SVG in 11 grafts in eight patients. The intermediate lesion was located in the aortic anastomosis, SVG body, or distal anastomosis in 16%, 58%, and 26% of grafts, respectively, and the mean percent diameter stenosis was 37 ± 9% by visual estimation. Percent stenosis was 30–39% in 16 grafts, 40–49% in seven grafts, and 50–60% in eight grafts. By quantitative coronary angiography, mean minimum lumen diameter was 1.85 ± 0.46 mm, reference diameter was 2.96 ±0.88 mm, percent diameter stenosis was 35 ± 13% and the lesion length was 8.9 ± 4.0 mm. None of those lesions was considered to be a culprit lesion and none of those lesions was stented during the index procedure. Baseline clinical and angiographic characteristics were largely similar between patients with and without intermediate SVG lesions with the exception that patients with intermediate lesions were older and more frequently presented with myocardial infarction (Table 1). 3.2. Outcomes of intermediate lesions During a median follow-up of 35 months, angiographic follow-up was available for 28 of 31 grafts in 25 of 27 patients (Fig. 1). Progression (defined as percent diameter stenosis ≥ 70% but b100% at followup angiography) was seen in 11 of 28 SVGs (39%) in 11 of 25 patients (44%) (Figs. 1 and 2). Four of the 28 grafts with intermediate lesions at baseline were found to be occluded at follow-up; all of those SVGs had received a stent as part of the SOS trial (Fig. 1). Seven of the 11 patients (64%) with intermediate SVG lesion progression presented with an acute coronary syndrome and PCI of the intermediate lesion was performed in 8 of the 11 (73%) patients (Fig. 3). The rate of intermediate SVG lesion progression at 12, 24 and 36 months was 28% and 47% and 84%, respectively (Fig. 4). Progression and occlusion rates were 50% and 25%, respectively, among patients with 50–59% stenosis at baseline, 33% and 0% among patients with 40–49% baseline stenosis, and 36% and 14% among patients with 30–39% baseline stenosis, respectively, (p = 0.50). Active smoking and diabetes were associated with a significantly higher probability of intermediate SVG lesion progression (p b 0.05 for each, Table 2).
Fig. 4. Kaplan–Meier curve of the intermediate saphenous vein graft lesion progression rate in the SOS trial.
(in approximately one of three patients), (b) occur mostly within the SVGs that require stenting, (c) have high rates of progression, and (d) progression frequently presents with an acute coronary syndrome. 4.1. Prevalence Our data indicate that within a population of patients who need PCI within a SVG, approximately one third of all patients and one fifth of all grafts have an intermediate SVG lesion. Moreover, most intermediate lesions are found within SVGs with severe lesions. This is in agreement with prior studies. Ellis et al. first reported that intermediate SVG lesions are common (1.4 ± 1.5 lesions per prior CABG patient undergoing clinically-indicated cardiac catheterization) [3]. Rodes-Cabau et al. screened 270 patients for inclusion in the VELETI study, of whom 57 patients (21%) had at least one intermediate SVG lesion. 4.2. Progression rates
4. Discussion The main findings of our study is that among patients undergoing SVG stenting, intermediate SVG lesions (a) are frequently encountered
A high rate of intermediate SVG lesion progression was seen in SOS patients: 28% at 1 year and 47% at 2 years. This is similar to prior studies. Ellis et al. first reported 45% and 18% 3-year incidence
Fig. 3. Presentation and outcomes of patients with intermediate saphenous vein graft lesion progression.
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Table 2 Baseline characteristics of patients with intermediate saphenous vein graft lesions, classified according to whether the intermediate lesions progressed or not.
Age (years)a Men, n (%) Inpatient, n (%) Ethnicity, n (%) White Black Hispanic Years since coronary artery bypass graft surgerya Indication for PCI, n (%) Stable angina Unstable angina NSTEMI Other Hypertension, n (%) Hyperlipidemia, n (%) Diabetes mellitus, n (%) Current smoking, n (%) Prior myocardial infarction, n (%) Body mass index (Kg/m2)a Statin prescribed at discharge Minimum lumen diameter, mma Reference vessel diameter, mma Percent diameter stenosisa Lesion length, mma Ejection fraction, n (%) Not done ≥ 50% 40–49% 30–39% b30% Intermediate lesion location, n (%) Proximal third Mid third Distal third Recipient vessel for each intermediate lesion graft, n (%) LAD/Diagonal Circumflex/OM RCA/PDA
Progression (patients = 11) (SVGs = 11)
No progression (patients = 12) (SVGs = 13)
P
68 ± 11 11 (100%) 10 (91%)
75 ± 9 12 (100%) 9 (75%)
0.11 1.0 0.31 0.37
11 (100%) 0 (0%) 0 (0%) 10 ± 5
10 (83.3%) 1 (8.3%) 1 (8.3%) 14 ± 7
3 (27%) 3 (27%) 5 (46%) 0 (0%) 10 (91%) 10 (91%) 7 (64%) 5 (45%) 7 (64%) 31 ± 4 10 (91%) 2 ± 0.48 3 ± 0.9 38 ± 11 8.2 ± 4
5 (42%) 2 (17%) 4 (33%) 1 (8%) 12 (100%) 10 (83%) 2 (17%) 1 (8%) 9 (75%) 28 ± 4 11 (92%) 1.8 ± 0.47 3 ± 0.87 36 ± 8 9.7 ± 4
1 7 2 1 0
0 (0%) 8 (67%) 2 (16.5%) 2 (16.5%) 0 (0%)
0.07 0.62
(9%) (64%) (18%) (9%) (0%)
0.29 0.59 0.02 0.04 0.55 0.18 0.95 0.21 0.58 0.6 0.37 0.72
0.64 1 (9%) 8 (73%) 2 (18%)
2 (15%) 7 (54%) 4 (31%) 0.98
2 (18%) 4 (36%) 5 (46%)
2 (15%) 5 (39%) 6 (46%)
PCI, percutaneous coronary intervention; NSTEMI, non ST-segment elevation myocardial infarction; SVG, saphenous vein graft; LAD, left anterior descending artery; OM, obtuse marginal; RCA, right coronary artery; PDA, posterior descending artery. a mean ± standard deviation.
of major adverse cardiac events in lesions with 41–50% and 31–40% diameter stenosis, respectively, at baseline [3]. In the post coronary artery bypass graft (POST-CABG) trial, patients with intermediate SVG lesions present at follow-up angiography had higher incidence of major adverse cardiac events (35% vs. 18%), and also had higher adjusted risk for death or myocardial infarction (RR = 2.2, 95% CI 1.3, 3.8) and coronary revascularization (RR = 3.3, 95% CI 2.0, 5.3). Rodes-Cabau et al. reported that 26% of 86 patients with intermediate SVG lesion had a cardiac event related to intermediate SVG lesion progression during a mean follow-up of 1.3 ± 1 years [5]. Finally, in the VELETI trial, 19% of the medically-treated patients (23% of the lesions) required target vessel revascularization [6] during 12 months of follow-up. This rapid progression is likely related to the nature of SVG atherosclerosis. SVG atherosclerosis is usually diffuse, concentric, and friable with a poorly developed or absent fibrous cap and little evidence of calcification, whereas native vessel atheroma is proximal, focal, eccentric, and nonfriable with a well-developed fibrous cap and frequent calcification [11]. Histologically, SVG atheromas tend to have more foam cells and inflammatory cells, including multinucleate giant cells, than native coronary atheromas [11]. SVGs have a more
powerful system of lipid biosynthesis and uptake, that may in part account for the accelerated formation of SVG atherosclerosis and forms the basis of using aggressive lipid lowering therapies to prevent SVG failure [11]. This rapid risk of progression in SVG intermediate lesions is in sharp contrast to the low progression rates of intermediate native coronary artery lesions. In the Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) study among patients undergoing PCI for acute coronary syndromes, the 3-year cumulative event rate judged to be related to not initially stented lesions was 11.6% [2]. In the Fractional Flow Reserve versus Angiography for Guiding Percutaneous Coronary Intervention (FAME) study, native coronary artery lesions that were not causing ischemia at baseline rarely progressed and medical therapy alone was superior to PCI in such lesions [1]. Two traditional CAD risk factors (smoking and diabetes) were found to be associated with intermediate SVG progression in our study. This is an important observation because both factors can be modified by pharmacologic or behavioral interventions. The prevalence of diabetes and obesity is very high in such patients: in a study of 367 prior CABG patients undergoing coronary angiography, 53% had diabetes and 52% had a body mass index >30 [12]. Exercise and dietary interventions may be challenging to implement but could have a significant impact on the well-being and risk of subsequent events of prior CABG patients presenting with SVG failure. 4.3. Presentation Progression of intermediate SVG lesions was not a benign event, as patients frequently presented with an acute coronary syndrome. This is similar to the presentation of SVG stent failure [8] and may also be related to the pathogenesis of SVG disease. Similarly, Rodes-Cabau et al. showed that three of the five patients who had intermediate SVG lesion progression in the VELETI trial presented with an acute coronary syndrome (and one patient had an occluded SVG) [6]. Although some of our patients presented with SVG occlusion, these were in stented SVGs, so it is not possible to determine whether this was due to stent failure or due to intermediate SVG lesion progression. 4.4. Implications Our findings have important implications. The poor natural history of intermediate SVG lesions suggests that aggressive treatment may be warranted. Aggressive lipid lowering therapy with statins is indicated [13–15] and the addition of niacin is currently being investigated in the ALPINE-SVG study (NCT01221402). Aggressive control of other coronary artery disease risk factors may also be of benefit and our data would suggest that particular attention on smoking cessation and diabetes control may be important to prevent progression of intermediate SVG lesions [12]. The VELETI trial results suggest that stenting intermediate SVG lesions with PES may be beneficial, but given the relatively high-risk of SVG stenting (periprocedural MI, restenosis) even when DES are used [16], larger studies are needed. The Sealing Moderate Coronary Saphenous VEin Graft Lesions With Paclitaxel-Eluting Stents (VELETI II, NCT01223443) is currently enrolling 450 patients with intermediate SVG lesions who are randomized to stenting with a PES or to standard medical treatment alone. 4.5. Limitations Our study is a post-hoc analysis of the SOS trial, and included relatively few patients. Some of the intermediate lesions were located in a stented graft and subsequent graft occlusion could not be attributed to intermediate lesion progression, as it could have been due to SVG stent failure. Patients underwent routine angiography which could
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have increased the rates of coronary revascularization, although all patients who underwent PCI, except one, presented with an acute coronary syndrome. 5. Conclusions In summary, intermediate SVG lesions are frequently found in patients undergoing SVG stenting, and have high rates of progression, often leading to acute coronary syndromes. Further study of pharmacologic and mechanical treatments to prevent progression of these lesions is needed. Disclosures - Dr. de Lemos has received speaker honoraria from Bristol-Myers Squibb/Sanofi-Aventis and consulting income from Johnson and Johnson. - Dr. Obel works predominantly with cardiac rhythm devices and has speaker agreements with St. Jude, Medtronic, and Boston Scientific. - Dr. Addo has served on the Speakers Bureau for Sanofi-Aventis, Merck-Schering, Eli Lilly and Daiichi-Sankyo. - Dr. Rossen participated in multicenter clinical studies supported by Boston Scientific. - Dr. Berger owns equity in Lumen, Inc. - Dr. Banerjee has served on the Speakers’ Bureau for St. Jude Medical Center, Medtronic Corp., and Johnson & Johnson and has received a research grant from Boston Scientific. - Dr. Brilakis has received speaker honoraria from St. Jude Medical Terumo and Bridgepoint Medical/Boston Scientific, research support from Guerbet and his spouse is an employee of Medtronic. References [1] Tonino PAL, De Bruyne B, Pijls NHJ, et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med 2009;360: 213–24. [2] Stone GW, Maehara A, Lansky AJ, et al. A prospective natural-history study of coronary atherosclerosis. N Engl J Med 2011;364:226–35.
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[3] Ellis SG, Brener SJ, DeLuca S, et al. Late myocardial ischemic events after saphenous vein graft intervention–importance of initially "nonsignificant" vein graft lesions. Am J Cardiol 1997;79:1460–4. [4] Knatterud GL, White C, Geller NL, et al. Angiographic changes in saphenous vein grafts are predictors of clinical outcomes. Am Heart J 2003;145:262–9. [5] Rodes-Cabau J, Facta A, Larose E, et al. Predictors of aorto-saphenous vein bypass narrowing late after coronary artery bypass grafting. Am J Cardiol 2007;100: 640–5. [6] Rodes-Cabau J, Bertrand OF, Larose E, et al. Comparison of plaque sealing with paclitaxel-eluting stents versus medical therapy for the treatment of moderate nonsignificant saphenous vein graft lesions. The Moderate VEin Graft LEsion Stenting With the Taxus Stent and Intravascular Ultrasound (VELETI) pilot trial. Circulation 2009;120:1978–86. [7] Brilakis ES, Lichtenwalter C, de Lemos JA, et al. A randomized controlled trial of a paclitaxel-eluting stent versus a similar bare-metal stent in saphenous vein graft lesions the SOS (Stenting of Saphenous Vein Grafts) trial. J Am Coll Cardiol 2009;53:919–28. [8] Lichtenwalter C, de Lemos JA, Roesle M, et al. Clinical presentation and angiographic characteristics of saphenous vein graft failure after stenting: insights from the SOS (stenting of saphenous vein grafts) trial. JACC Cardiovasc Interv 2009;2:855–60. [9] Badhey N, Lichtenwalter C, de Lemos JA, et al. Contemporary use of embolic protection devices in saphenous vein graft interventions: insights from the stenting of saphenous vein grafts trial. Catheter Cardiovasc Interv 2010;76:263–9. [10] Brilakis ES, Lichtenwalter C, Abdel-karim A-rR, et al. Continued benefit from paclitaxel-eluting compared with bare-metal stent implantation in saphenous vein graft lesions during long-term follow-up of the SOS (Stenting of Saphenous Vein Grafts) trial. J Am Coll Cardiol Intv 2011;4:176–82. [11] Motwani JG, Topol EJ. Aortocoronary saphenous vein graft disease: pathogenesis, predisposition, and prevention. Circulation 1998;97:916–31. [12] Boatman DM, Saeed B, Varghese I, et al. Prior coronary artery bypass graft surgery patients undergoing diagnostic coronary angiography have multiple uncontrolled coronary artery disease risk factors and high risk for cardiovascular events. Heart Vessels 2009;24:241–6. [13] Brilakis ES, de Lemos JA, Cannon CP, et al. Outcomes of patients with acute coronary syndrome and previous coronary artery bypass grafting (from the Pravastatin or Atorvastatin Evaluation and Infection Therapy [PROVE IT-TIMI 22] and the Aggrastat to Zocor [A to Z] trials). Am J Cardiol 2008;102:552–8. [14] Shah SJ, Waters DD, Barter P, et al. Intensive lipid-lowering with atorvastatin for secondary prevention in patients after coronary artery bypass surgery. J Am Coll Cardiol 2008;51:1938–43. [15] Wee CC, Girotra S, Weinstein AR, Mittleman MA, Mukamal KJ. The relationship between obesity and atherosclerotic progression and prognosis among patients with coronary artery bypass grafts the effect of aggressive statin therapy. J Am Coll Cardiol 2008;52:620–5. [16] Brilakis ES, Saeed B, Banerjee S. Drug-eluting stents in saphenous vein graft interventions: a systematic review. EuroIntervention 2010;5:722–30.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Prevalence and outcomes of intermediate saphenous vein graft lesions: Findings from the stenting of saphenous vein grafts randomized-controlled trial Abdul-rahman R. Abdel-karim a, b, Monica Da Silva a, b, Christopher Lichtenwalter c, James A. de Lemos a, b, Owen Obel a, b, Tayo Addo a, b, Michele Roesle a, Donald Haagen a, Bavana V. Rangan a, Lorenza Makke a, Omar M. Jeroudi a, b, Deepa Raghunathan a, b, Bilal Saeed d, Joseph K. Bissett e, Rajesh Sachdeva e, Vassilios V. Voudris f, Panagiotis Karyofillis f, Biswajit Kar g, James Rossen h, Panayotis Fasseas i, Peter Berger j, Subhash Banerjee a, b, Emmanouil S. Brilakis a, b,⁎ a
Veteran Affairs North Texas Healthcare System, Dallas, TX, USA University of Texas Southwestern Medical Center, Dallas, TX, USA The Cardiovascular and Arrhythmia Institute, Mesa, AZ, USA d Geisinger Medical Center, Danville, PA, USA e Central Arkansas Veterans Healthcare System and University of Arkansas for Medical Sciences, Little Rock, AR, USA f Onassis Cardiac Surgery Center, Athens, Greece g Michael E. DeBakey Veterans Affairs Medical Center, Houston TX, USA h Iowa City Veteran Affairs Medical Center, Iowa City, IA, USA i Medical College of Wisconsin, Milwaukee, WI, USA j Geisinger Clinic, Danville, PA, USA b c
a r t i c l e
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Article history: Received 28 November 2012 Accepted 9 March 2013 Available online 3 April 2013 Keywords: Saphenous vein grafts Percutaneous Coronary Interventions Stents
a b s t r a c t Background: We sought to examine the prevalence and progression rate of intermediate saphenous vein graft (SVG) lesions in the Stenting Of Saphenous vein grafts (SOS) trial. Methods: The baseline and follow-up angiograms of 80 patients participating in the SOS trial were analyzed to determine the prevalence of intermediate (30–60% angiographic diameter stenosis) SVG lesions and their progression rate. Results: At least one intermediate SVG lesion was present in 31 of 143 (22%) SVGs in 27 of 80 (34%) patients. Most intermediate lesions were present in the SOS stented SVGs (20 grafts in 19 patients). During a median follow-up of 35 months, angiographic follow-up was available for 28 grafts in 25 patients. Progression (defined as percent diameter stenosis ≥70% but b100% at follow-up angiography) was seen in 11 of 28 SVGs (39%) in 11 of 25 patients (44%). Progression rate at 12, 24 and 36 months was 28% and 47% and 84%, respectively. Seven of 11 patients (64%) with intermediate SVG lesion progression presented with an acute coronary syndrome and 8 (73%) underwent PCI. Four of the 28 grafts with intermediate lesions at baseline were 100% occluded at follow-up; all of those SVGs had received a stent in another location in the SVG as part of the SOS trial. Conclusions: Intermediate SVG lesions are common in patients undergoing SVG stenting, have high rates of progression and frequently present with an acute coronary syndrome. Further study of pharmacologic and mechanical treatments to prevent progression of these lesions is needed. Published by Elsevier Ireland Ltd.
1. Introduction In native coronary arteries intermediate stenoses have a favorable prognosis with low rates of rapid progression and lesion-related acute coronary syndromes [1,2]. In contrast, intermediate saphenous
Abbreviations: CABG, Coronary Artery Bypass Graft; HDL, High Density Lipoprotein; LDL, Low Density Lipoprotein; PCI, Percutaneous Coronary Intervention; SOS, Stenting Of Saphenous vein grafts trial; SVG, Saphenous Vein Graft. ⁎ Corresponding author at: Dallas VA Medical Center (111A), 4500 South Lancaster Road, Dallas, TX 75216, USA. Tel.: +1 214 857 1547; fax: +1 214 302 1341. E-mail address: [email protected] (E.S. Brilakis). 0167-5273/$ – see front matter. Published by Elsevier Ireland Ltd. http://dx.doi.org/10.1016/j.ijcard.2013.03.006
vein graft (SVG) lesions often progress rapidly [3–6], and have been associated with a two-fold increase in overall mortality independently of other comorbidities [4]. The VELETI (Moderate VEin Graft LEsion Stenting With the Taxus Stent and Intravascular Ultrasound) trial suggested that prophylactic stenting of intermediate SVG lesions with a paclitaxel-eluting stent (PES) may provide improved outcomes compared to medical therapy alone [6]. The Stenting Of Saphenous vein graft (SOS) trial (NCT00247208) randomized 80 patients with severe SVG lesions to PES or a similar bare metal stent (BMS) and demonstrated improved angiographic and clinical outcomes with PES [7–10]. An intriguing observation from SOS was that 2/3 of the target vessel revascularizations in
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PES-treated patients were due to progression of intermediate SVG lesions [7]. In the present study we sought to determine the prevalence and outcomes of intermediate SVG lesions in the SOS study population. 2. Methods 2.1. Patient population The design and primary results of the SOS trial have been published [7,10]. Briefly, the SOS was a multicenter, randomized, controlled trial that compared the clinical and angiographic outcomes after implantation of a PES vs. a similar BMS in SVG lesions. Patients were asked to return for follow-up angiography 12 months post stenting and were also followed clinically. Median clinical follow-up was 35 months. The author(s) of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.
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2.2. Angiographic analysis The baseline and follow-up angiograms were evaluated to determine whether an intermediate lesion (defined as 30–60% angiographic diameter stenosis by visual estimation, not considered to be responsible for the patient’s clinical presentation) was present and whether it progressed during follow-up. Assessment was performed blinded to the patient’s treatment allocation. Subsequently, quantitative angiographic analyses were performed using the CAAS automated edge detection system version 5.4. (Pie Medical Imaging, Maastricht, the Netherlands). The projection that best showed the stenosis in its tightest view was selected. Patients were considered to have had progression of the intermediate SVG lesion if it was found to have ≥70% but b100% angiographic diameter stenosis at follow-up. Patients with 100% occluded SVGs at follow-up were analyzed separately, because it was not possible to determine whether occlusion was due to progression of the intermediate SVG lesion or due to restenosis or thrombosis of the SOS-target SVG. If a patient had >1 intermediate lesion and at least one of those lesions progressed, he was considered to be a “progressor”.
Fig. 1. Prevalence and outcomes of patients (panel A) and saphenous vein grafts (panel B) with intermediate saphenous vein graft lesions. 1, two patients in this group had two saphenous vein grafts with intermediate lesions: in the first patient one saphenous vein graft progressed and one was occluded at follow-up and in the other patient one saphenous vein graft progressed and one saphenous vein graft did not progress. 2, two patients in this group had two saphenous vein grafts with intermediate lesions: in the first patient one saphenous vein graft did not progress and one was occluded at follow-up and in the other patient one saphenous vein graft did not progress and another saphenous vein graft was not injected at follow-up angiography.
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Table 1 Baseline characteristics of the study population. Intermediate lesion No intermediate lesion P (patients = 53) (patients = 27) (SVGs = 112) (SVGs = 31) Age (years)a Men, n (%) Inpatient, n (%) Ethnicity, n (%) White Black Hispanic Years since coronary artery bypass graft surgerya Indication for PCI, n (%) Stable angina Unstable angina NSTEMI Other Hypertension, n (%) Hyperlipidemia, n (%) Diabetes mellitus, n (%) Current smoking, n (%) Prior myocardial infarction, n (%) Body mass index (kg/m2)a Statin at baseline, n (%) Ejection fraction, n (%) Not done ≥ 50% 40–49% 30–39% b30% Recipient vessel for all patent SVGs, n (%) LAD/Diagonal Circumflex/OM RCA/PDA Number of SVGs treated per patienta 1 2 Number of lesions treated per patienta SOS lesion location, n (%) Aortic anastomosis Proximal third Mid third Distal third Coronary anastomosis Recipient vessel for each SOS graft, n (%) LAD/Diagonal Circumflex/OM RCA/PDA Pre-stenting TIMI flow, n (%) 1 2 3 Post-stenting TIMI flow, n (%) 2 3 Embolic protection device use, n (%) Predilatation, n (%) Postdilatation, n (%) Maximum balloon diameter (mm)a Maximum inflation pressure (atm)a Contrast utilization (mL)a Fluoroscopy time (min)a Medications at the time of PCI Anticoagulation, n (%) Unfractionated heparin
71 ± 10 27 (100%) 21 (78%)
64 ± 8 53(100%) 35 (66%)
25 (93%) 1 (4%) 1 (4%) 12 ± 6
51 (96%) 1 (2%) 1 (2%) 11 ± 6
10 (37%) 6 (22%) 10 (37%) 1 (4%) 26 (96%) 24 (89%) 11 (41%) 7 (26%) 18 (67%)
15 (28.5%) 24 (45%) 8 (15%) 6 (11.5%) 49 (92.45%) 53 (100%) 21 (40%) 14 (26%) 28 (53%)
30 ± 4 23 (85%)
29 ± 4 48 (91%)
1 (3.5%) 18 (67%) 4 (15%) 3 (11%) 1 (3.5%)
6 (11%) 25 (47%) 14 (26.5%) 5 (9.5%) 3 (6%)
0.004a 1.0 0.28 0.78
0.56
Intermediate lesion No intermediate lesion P (patients = 53) (patients = 27) (SVGs = 112) (SVGs = 31) Bivalirudin Glycoprotein IIb/IIIa inhibitor, n (%) Post PCI myocardial infarction, n (%)
4 (15%) 3 (11%)
12 (23%) 6 (11%)
0.41 0.98
2/25 (8%)
2/40 (5%)
0.62
PCI, percutaneous coronary intervention; NSTEMI, non ST-segment elevation myocardial infarction; SVG, saphenous vein graft; LAD, left anterior descending artery; OM, obtuse marginal; RCA, right coronary artery; PDA, posterior descending artery; TIMI, thrombolysis in myocardial infarction. a mean ± standard deviation.
0.046 2.3. Statistical analysis
0.5 0.013 0.92 0.96 0.24
Continuous parameters were presented as mean ± standard deviation and were compared using the Wilcoxon rank-sum test. Nominal variables were presented as percentages and compared using the chi-square test. The incidence of intermediate SVG lesion progression was calculated using the Kaplan–Meier method. A p-value b0.05 was considered statistically significant for all analyses. Analyses were performed using JMP 8.0 (SAS Institute, Cary, North Carolina).
0.43 0.47 0.47
3. Results 3.1. Prevalence of intermediate SVG lesions
0.47 5 (16%) 13 (42%) 13 (42%) 1.15 ± 0.36
29 (26%) 46 (41%) 37 (33%) 1.07 ± 0.26
23 (85%) 4 (15%) 1.33 ± 0.62
49 (92%) 4 (8%) 1.43 ± 0.69
12 (33.3%) 7 (19.5%) 13 (36%) 1 (3%) 3 (8.3%)
18 (24%) 20 (26%) 22 (28%) 11 (15%) 5 (7%)
0.31
An intermediate SVG lesion was present in 31 of 143 (22%) patent SVGs in 27 of 80 (34%) SOS study patients (Fig. 1). The intermediate lesion
0.31 0.495 0.29
0.475 7 (23%) 11 (35%) 13 (42%)
18 (31.5%) 22 (38.5%) 17 (30%) 0.07
0 (0%) 8 (22%) 28 (78%)
4 (5%) 7 (9%) 65 (86%) 0.019
4 (11%) 32 (89%) 24 (67%)
1 (1%) 75 (99%) 36 (47%)
0.056
10 (28%) 11 (31%) 3.4 ± 0.5
25 (33%) 12 (16%) 3.1 ± 0.45
0.585 0.07 0.01
17.5 ± 2.4
16.5 ± 3.0
0.057
257 ± 84 21 ± 7
261 ± 109 20 ± 11
0.77 0.21
23 (85%)
42 (79%)
0.52
Fig. 2. Example of an intermediate saphenous vein graft lesion progression from baseline (panel A) to follow-up performed 15 months later (panel B).
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was present in a stented SVG in 20 grafts in 19 patients and in a non-stented SVG in 11 grafts in eight patients. The intermediate lesion was located in the aortic anastomosis, SVG body, or distal anastomosis in 16%, 58%, and 26% of grafts, respectively, and the mean percent diameter stenosis was 37 ± 9% by visual estimation. Percent stenosis was 30–39% in 16 grafts, 40–49% in seven grafts, and 50–60% in eight grafts. By quantitative coronary angiography, mean minimum lumen diameter was 1.85 ± 0.46 mm, reference diameter was 2.96 ±0.88 mm, percent diameter stenosis was 35 ± 13% and the lesion length was 8.9 ± 4.0 mm. None of those lesions was considered to be a culprit lesion and none of those lesions was stented during the index procedure. Baseline clinical and angiographic characteristics were largely similar between patients with and without intermediate SVG lesions with the exception that patients with intermediate lesions were older and more frequently presented with myocardial infarction (Table 1). 3.2. Outcomes of intermediate lesions During a median follow-up of 35 months, angiographic follow-up was available for 28 of 31 grafts in 25 of 27 patients (Fig. 1). Progression (defined as percent diameter stenosis ≥ 70% but b100% at followup angiography) was seen in 11 of 28 SVGs (39%) in 11 of 25 patients (44%) (Figs. 1 and 2). Four of the 28 grafts with intermediate lesions at baseline were found to be occluded at follow-up; all of those SVGs had received a stent as part of the SOS trial (Fig. 1). Seven of the 11 patients (64%) with intermediate SVG lesion progression presented with an acute coronary syndrome and PCI of the intermediate lesion was performed in 8 of the 11 (73%) patients (Fig. 3). The rate of intermediate SVG lesion progression at 12, 24 and 36 months was 28% and 47% and 84%, respectively (Fig. 4). Progression and occlusion rates were 50% and 25%, respectively, among patients with 50–59% stenosis at baseline, 33% and 0% among patients with 40–49% baseline stenosis, and 36% and 14% among patients with 30–39% baseline stenosis, respectively, (p = 0.50). Active smoking and diabetes were associated with a significantly higher probability of intermediate SVG lesion progression (p b 0.05 for each, Table 2).
Fig. 4. Kaplan–Meier curve of the intermediate saphenous vein graft lesion progression rate in the SOS trial.
(in approximately one of three patients), (b) occur mostly within the SVGs that require stenting, (c) have high rates of progression, and (d) progression frequently presents with an acute coronary syndrome. 4.1. Prevalence Our data indicate that within a population of patients who need PCI within a SVG, approximately one third of all patients and one fifth of all grafts have an intermediate SVG lesion. Moreover, most intermediate lesions are found within SVGs with severe lesions. This is in agreement with prior studies. Ellis et al. first reported that intermediate SVG lesions are common (1.4 ± 1.5 lesions per prior CABG patient undergoing clinically-indicated cardiac catheterization) [3]. Rodes-Cabau et al. screened 270 patients for inclusion in the VELETI study, of whom 57 patients (21%) had at least one intermediate SVG lesion. 4.2. Progression rates
4. Discussion The main findings of our study is that among patients undergoing SVG stenting, intermediate SVG lesions (a) are frequently encountered
A high rate of intermediate SVG lesion progression was seen in SOS patients: 28% at 1 year and 47% at 2 years. This is similar to prior studies. Ellis et al. first reported 45% and 18% 3-year incidence
Fig. 3. Presentation and outcomes of patients with intermediate saphenous vein graft lesion progression.
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Table 2 Baseline characteristics of patients with intermediate saphenous vein graft lesions, classified according to whether the intermediate lesions progressed or not.
Age (years)a Men, n (%) Inpatient, n (%) Ethnicity, n (%) White Black Hispanic Years since coronary artery bypass graft surgerya Indication for PCI, n (%) Stable angina Unstable angina NSTEMI Other Hypertension, n (%) Hyperlipidemia, n (%) Diabetes mellitus, n (%) Current smoking, n (%) Prior myocardial infarction, n (%) Body mass index (Kg/m2)a Statin prescribed at discharge Minimum lumen diameter, mma Reference vessel diameter, mma Percent diameter stenosisa Lesion length, mma Ejection fraction, n (%) Not done ≥ 50% 40–49% 30–39% b30% Intermediate lesion location, n (%) Proximal third Mid third Distal third Recipient vessel for each intermediate lesion graft, n (%) LAD/Diagonal Circumflex/OM RCA/PDA
Progression (patients = 11) (SVGs = 11)
No progression (patients = 12) (SVGs = 13)
P
68 ± 11 11 (100%) 10 (91%)
75 ± 9 12 (100%) 9 (75%)
0.11 1.0 0.31 0.37
11 (100%) 0 (0%) 0 (0%) 10 ± 5
10 (83.3%) 1 (8.3%) 1 (8.3%) 14 ± 7
3 (27%) 3 (27%) 5 (46%) 0 (0%) 10 (91%) 10 (91%) 7 (64%) 5 (45%) 7 (64%) 31 ± 4 10 (91%) 2 ± 0.48 3 ± 0.9 38 ± 11 8.2 ± 4
5 (42%) 2 (17%) 4 (33%) 1 (8%) 12 (100%) 10 (83%) 2 (17%) 1 (8%) 9 (75%) 28 ± 4 11 (92%) 1.8 ± 0.47 3 ± 0.87 36 ± 8 9.7 ± 4
1 7 2 1 0
0 (0%) 8 (67%) 2 (16.5%) 2 (16.5%) 0 (0%)
0.07 0.62
(9%) (64%) (18%) (9%) (0%)
0.29 0.59 0.02 0.04 0.55 0.18 0.95 0.21 0.58 0.6 0.37 0.72
0.64 1 (9%) 8 (73%) 2 (18%)
2 (15%) 7 (54%) 4 (31%) 0.98
2 (18%) 4 (36%) 5 (46%)
2 (15%) 5 (39%) 6 (46%)
PCI, percutaneous coronary intervention; NSTEMI, non ST-segment elevation myocardial infarction; SVG, saphenous vein graft; LAD, left anterior descending artery; OM, obtuse marginal; RCA, right coronary artery; PDA, posterior descending artery. a mean ± standard deviation.
of major adverse cardiac events in lesions with 41–50% and 31–40% diameter stenosis, respectively, at baseline [3]. In the post coronary artery bypass graft (POST-CABG) trial, patients with intermediate SVG lesions present at follow-up angiography had higher incidence of major adverse cardiac events (35% vs. 18%), and also had higher adjusted risk for death or myocardial infarction (RR = 2.2, 95% CI 1.3, 3.8) and coronary revascularization (RR = 3.3, 95% CI 2.0, 5.3). Rodes-Cabau et al. reported that 26% of 86 patients with intermediate SVG lesion had a cardiac event related to intermediate SVG lesion progression during a mean follow-up of 1.3 ± 1 years [5]. Finally, in the VELETI trial, 19% of the medically-treated patients (23% of the lesions) required target vessel revascularization [6] during 12 months of follow-up. This rapid progression is likely related to the nature of SVG atherosclerosis. SVG atherosclerosis is usually diffuse, concentric, and friable with a poorly developed or absent fibrous cap and little evidence of calcification, whereas native vessel atheroma is proximal, focal, eccentric, and nonfriable with a well-developed fibrous cap and frequent calcification [11]. Histologically, SVG atheromas tend to have more foam cells and inflammatory cells, including multinucleate giant cells, than native coronary atheromas [11]. SVGs have a more
powerful system of lipid biosynthesis and uptake, that may in part account for the accelerated formation of SVG atherosclerosis and forms the basis of using aggressive lipid lowering therapies to prevent SVG failure [11]. This rapid risk of progression in SVG intermediate lesions is in sharp contrast to the low progression rates of intermediate native coronary artery lesions. In the Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) study among patients undergoing PCI for acute coronary syndromes, the 3-year cumulative event rate judged to be related to not initially stented lesions was 11.6% [2]. In the Fractional Flow Reserve versus Angiography for Guiding Percutaneous Coronary Intervention (FAME) study, native coronary artery lesions that were not causing ischemia at baseline rarely progressed and medical therapy alone was superior to PCI in such lesions [1]. Two traditional CAD risk factors (smoking and diabetes) were found to be associated with intermediate SVG progression in our study. This is an important observation because both factors can be modified by pharmacologic or behavioral interventions. The prevalence of diabetes and obesity is very high in such patients: in a study of 367 prior CABG patients undergoing coronary angiography, 53% had diabetes and 52% had a body mass index >30 [12]. Exercise and dietary interventions may be challenging to implement but could have a significant impact on the well-being and risk of subsequent events of prior CABG patients presenting with SVG failure. 4.3. Presentation Progression of intermediate SVG lesions was not a benign event, as patients frequently presented with an acute coronary syndrome. This is similar to the presentation of SVG stent failure [8] and may also be related to the pathogenesis of SVG disease. Similarly, Rodes-Cabau et al. showed that three of the five patients who had intermediate SVG lesion progression in the VELETI trial presented with an acute coronary syndrome (and one patient had an occluded SVG) [6]. Although some of our patients presented with SVG occlusion, these were in stented SVGs, so it is not possible to determine whether this was due to stent failure or due to intermediate SVG lesion progression. 4.4. Implications Our findings have important implications. The poor natural history of intermediate SVG lesions suggests that aggressive treatment may be warranted. Aggressive lipid lowering therapy with statins is indicated [13–15] and the addition of niacin is currently being investigated in the ALPINE-SVG study (NCT01221402). Aggressive control of other coronary artery disease risk factors may also be of benefit and our data would suggest that particular attention on smoking cessation and diabetes control may be important to prevent progression of intermediate SVG lesions [12]. The VELETI trial results suggest that stenting intermediate SVG lesions with PES may be beneficial, but given the relatively high-risk of SVG stenting (periprocedural MI, restenosis) even when DES are used [16], larger studies are needed. The Sealing Moderate Coronary Saphenous VEin Graft Lesions With Paclitaxel-Eluting Stents (VELETI II, NCT01223443) is currently enrolling 450 patients with intermediate SVG lesions who are randomized to stenting with a PES or to standard medical treatment alone. 4.5. Limitations Our study is a post-hoc analysis of the SOS trial, and included relatively few patients. Some of the intermediate lesions were located in a stented graft and subsequent graft occlusion could not be attributed to intermediate lesion progression, as it could have been due to SVG stent failure. Patients underwent routine angiography which could
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have increased the rates of coronary revascularization, although all patients who underwent PCI, except one, presented with an acute coronary syndrome. 5. Conclusions In summary, intermediate SVG lesions are frequently found in patients undergoing SVG stenting, and have high rates of progression, often leading to acute coronary syndromes. Further study of pharmacologic and mechanical treatments to prevent progression of these lesions is needed. Disclosures - Dr. de Lemos has received speaker honoraria from Bristol-Myers Squibb/Sanofi-Aventis and consulting income from Johnson and Johnson. - Dr. Obel works predominantly with cardiac rhythm devices and has speaker agreements with St. Jude, Medtronic, and Boston Scientific. - Dr. Addo has served on the Speakers Bureau for Sanofi-Aventis, Merck-Schering, Eli Lilly and Daiichi-Sankyo. - Dr. Rossen participated in multicenter clinical studies supported by Boston Scientific. - Dr. Berger owns equity in Lumen, Inc. - Dr. Banerjee has served on the Speakers’ Bureau for St. Jude Medical Center, Medtronic Corp., and Johnson & Johnson and has received a research grant from Boston Scientific. - Dr. Brilakis has received speaker honoraria from St. Jude Medical Terumo and Bridgepoint Medical/Boston Scientific, research support from Guerbet and his spouse is an employee of Medtronic. References [1] Tonino PAL, De Bruyne B, Pijls NHJ, et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med 2009;360: 213–24. [2] Stone GW, Maehara A, Lansky AJ, et al. A prospective natural-history study of coronary atherosclerosis. N Engl J Med 2011;364:226–35.
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[3] Ellis SG, Brener SJ, DeLuca S, et al. Late myocardial ischemic events after saphenous vein graft intervention–importance of initially "nonsignificant" vein graft lesions. Am J Cardiol 1997;79:1460–4. [4] Knatterud GL, White C, Geller NL, et al. Angiographic changes in saphenous vein grafts are predictors of clinical outcomes. Am Heart J 2003;145:262–9. [5] Rodes-Cabau J, Facta A, Larose E, et al. Predictors of aorto-saphenous vein bypass narrowing late after coronary artery bypass grafting. Am J Cardiol 2007;100: 640–5. [6] Rodes-Cabau J, Bertrand OF, Larose E, et al. Comparison of plaque sealing with paclitaxel-eluting stents versus medical therapy for the treatment of moderate nonsignificant saphenous vein graft lesions. The Moderate VEin Graft LEsion Stenting With the Taxus Stent and Intravascular Ultrasound (VELETI) pilot trial. Circulation 2009;120:1978–86. [7] Brilakis ES, Lichtenwalter C, de Lemos JA, et al. A randomized controlled trial of a paclitaxel-eluting stent versus a similar bare-metal stent in saphenous vein graft lesions the SOS (Stenting of Saphenous Vein Grafts) trial. J Am Coll Cardiol 2009;53:919–28. [8] Lichtenwalter C, de Lemos JA, Roesle M, et al. Clinical presentation and angiographic characteristics of saphenous vein graft failure after stenting: insights from the SOS (stenting of saphenous vein grafts) trial. JACC Cardiovasc Interv 2009;2:855–60. [9] Badhey N, Lichtenwalter C, de Lemos JA, et al. Contemporary use of embolic protection devices in saphenous vein graft interventions: insights from the stenting of saphenous vein grafts trial. Catheter Cardiovasc Interv 2010;76:263–9. [10] Brilakis ES, Lichtenwalter C, Abdel-karim A-rR, et al. Continued benefit from paclitaxel-eluting compared with bare-metal stent implantation in saphenous vein graft lesions during long-term follow-up of the SOS (Stenting of Saphenous Vein Grafts) trial. J Am Coll Cardiol Intv 2011;4:176–82. [11] Motwani JG, Topol EJ. Aortocoronary saphenous vein graft disease: pathogenesis, predisposition, and prevention. Circulation 1998;97:916–31. [12] Boatman DM, Saeed B, Varghese I, et al. Prior coronary artery bypass graft surgery patients undergoing diagnostic coronary angiography have multiple uncontrolled coronary artery disease risk factors and high risk for cardiovascular events. Heart Vessels 2009;24:241–6. [13] Brilakis ES, de Lemos JA, Cannon CP, et al. Outcomes of patients with acute coronary syndrome and previous coronary artery bypass grafting (from the Pravastatin or Atorvastatin Evaluation and Infection Therapy [PROVE IT-TIMI 22] and the Aggrastat to Zocor [A to Z] trials). Am J Cardiol 2008;102:552–8. [14] Shah SJ, Waters DD, Barter P, et al. Intensive lipid-lowering with atorvastatin for secondary prevention in patients after coronary artery bypass surgery. J Am Coll Cardiol 2008;51:1938–43. [15] Wee CC, Girotra S, Weinstein AR, Mittleman MA, Mukamal KJ. The relationship between obesity and atherosclerotic progression and prognosis among patients with coronary artery bypass grafts the effect of aggressive statin therapy. J Am Coll Cardiol 2008;52:620–5. [16] Brilakis ES, Saeed B, Banerjee S. Drug-eluting stents in saphenous vein graft interventions: a systematic review. EuroIntervention 2010;5:722–30.