Stenting of saphenous vein grafts with drug eluting stents: maybe not as good as in native vessels

EDITORIAL

^IDepartment of Cardiology - Cleveland Clinic - Cleveland, OH, USA

^IIInstituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (InCor/HCFMUSP) - São Paulo, SP, Brasil

Correspondência

Since the introduction by Floyd Loop at the Cleveland Clinic of the internal mammary artery (IMA) as an arterial graft to bypass the left anterior descending artery (LAD), it has been the gold standard conduit for revascularization, principally because it demonstrated its potent survival benefit in the long term follow-up.¹ However, patients with multivessel coronary artery disease (CAD) undergoing coronary artery bypass graft (CABG) still required the saphenous vein grafts (SVG) as a bypass conduit to non-LAD coronary arteries and unlike the extremely high durability and patency rates for the LIMA graft, 50% of SVGs develop severe disease or occlusion at 10 years.

Over the last decades, percutaneous coronary intervention (PCI) has offered a less invasive revascularization alternative compared to CABG, particularly for patients with less extensive obstructive CAD. Interventional cardiology has rapidly progressed, with clear improvement of the technique that has permitted the widespread use of stents in more than 95% of interventional procedures, including the treatment of more complex stenosis such as long lesions, small vessels, multivessel disease, and SVGs.^2-5

Currently, PCI of SVG comprise about 10% of all interventional procedures in many centers⁶ and is associated with a higher risk of both emboli-related myocardial infarction (MI) and restenosis, despite major advances in pharmacological and device therapy.⁷ Thus, although drug-eluting stents (DES) vs. bare metal stents (BMS) have shown better outcomes in the treatment of native coronary artery disease,⁵ most major studies excluded or had few patients with SVG lesions, and studies comparing DES vs. BMS in SVG interventions have yielded conflicting results, and most of them do not have long-term follow-up.^2,7-10

The article by Collet et al.¹¹ published in this issue of the Revista Brasileira de Cardiologia Invasiva provides additional insights into the comparison of DES vs. BMS for the treatment of SVGs, using data from a Registry that included consecutive patients enrolled and divided according to the type of stent deployed (209 with DES and 99 with BMS). The rationale of this study is this lack of large studies with long-term follow-up (> 1 year). The authors found that during hospitalization, there was a trend toward higher major adverse cardiac events (MACE) in the DES vs. BMS group (12% vs. 5.1%, respectively; P = 0.06). However, after up to 24 months of follow-up, MACE was equivalent between both groups (17.2% vs. 18.2%, respectively; P = 0.87), as was definite/probable stent thrombosis (2.3% vs. 2%, respectively; P = 0.94). In conclusion, in this real world series of complex patients, the authors found no long-term safety concerns related to the use of DES in the treatment of SVG lesions, with similar rates of cardiac death/MI/ stent thrombosis in both cohorts, but no demonstrable benefit in reduction in subsequent revascularization. Based on the results of the present study and given the post-hoc nature of this paper and the small numbers of patients, firm conclusions may be difficult to draw from the present analysis and larger randomized studies addressing these issues are warranted.

Nevertheless, recent meta-analysis combining randomized and observational studies have suggested benefit from DES vs. BMS in the treatment of SVG lesions.^2,7-10,12 Hakeem et al.⁹ showed a lower rate of MACE (19% vs. 28%, respectively; P < 0.00001), driven by lower rates of death (P = 0.02), MI (P = 0.007), and target vessel revascularization (TVR) (P = 0.0002). There were no differences in stent thrombosis (1% vs. 1.7%, respectively; P = 0.08). While a reduction in TVR is plausible, one might wonder how use of a DES instead of a BMS might reduce death and MI, leaving open the question as to whether the result was due to concomitant drug therapy or that DES were used in patients with fewer major comorbidities. On the other hand, Lee et al.¹² demonstrated that TVR was lower for SVG intervention with a DES [odds ratio (OR) 0.59, 95% confidence interval (CI) 0.49 to 0.72], with also lower rates of MI (OR 0.69, 95% CI 0.49 to 0.99), but no differences in stent thrombosis or death between both groups. Thus, both studies showed lower rates of TVR.

Another interesting phenomenon seen in some trials that pursued late follow-up is the so called "late catchup phenomenon" in TVR. This because the initial benefit seen in the first years in TVR is not sustained with longer-term follow-up.¹⁰ TVR after SVG intervention occurs more commonly at untreated sites other than at the target lesion after the first year.⁸ This progression of disease at SVG sites other than the target lesion might account for most of the late TVR.

Another important reason for the lack of benefit of DES to treat SVG is that the pathophysiology of atherosclerosis is different among veins and arteries. Vein grafts are subjected to unique mechanisms of graft failure, such as anastomotic lesions, kinking, and entrapment, in which DES may offer no benefit over BMS. The lack of long-term benefit of DES in SVG lesions is also likely related to a progressive degenerative process that is not necessarily stopped by a very focal or segmental therapy such as stenting. Importantly, once SVGs begin to degenerate, there is a high rate of graft failure and much more rapid progression of disease than in native vessels.^7,8

The largest, most important randomized study in this topic is the recently presented ISAR-CABG trial that showed at one-year follow up, that DES group had a 35% lower incidence of the primary composite end point (death, MI, and TLR) compared to BMS group (16.5% vs. 22.1%; P = 0.028).¹³ Not surprisingly, this difference was mainly driven by the decrease in target lesion revascularization (7.2% vs. 12.9%; P = 0.020) with little difference in other factors comprising MACE. The longer term follow-up of this study should provide better answers to the question of the exact benefits of DES to treat SVGs.

CONFLICT OF INTEREST

The authors have no conflict of interest to declare.

REFERENCES

• 1. Loop FD, Lytle BW, Cosgrove DM, Stewart RW, Goormastic M, Williams GW, et al. Influence of the internal-mammary-artery graft on 10-year survival and other cardiac events. N Engl J Med. 1986;314(1):1-6.
• 2. Brilakis ES, Lichtenwalter C, de Lemos JA, Roesle M, Obel O, Haagen D, 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(11):919-28.
• 3. Serruys PW, de Jaegere P, Kiemeneij F, Macaya C, Rutsch W, Heyndrickx G, et al. A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. Benestent Study Group. N Engl J Med. 1994;331(8):489-95.
• 4. Wiisanen ME, Abdel-Latif A, Mukherjee D, Ziada KM. Drug-eluting stents versus bare-metal stents in saphenous vein graft interventions: a systematic review and meta-analysis. JACC Cardiovasc Interv. 2010;3(12):1262-73.
• 5. Stone GW, Ellis SG, Cox DA, Hermiller J, O'Shaughnessy C, Mann JT, et al. A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease. N Engl J Med. 2004;350(3):221-31.
• 6. Coolong A, Baim DS, Kuntz RE, O'Malley AJ, Marulkar S, Cutlip DE, et al. Saphenous vein graft stenting and major adverse cardiac events: a predictive model derived from a pooled analysis of 3958 patients. Circulation. 2008;117(6):790-7.
• 7. Keeley EC, Velez CA, O'Neill WW, Safian RD. Long-term clinical outcome and predictors of major adverse cardiac events after percutaneous interventions on saphenous vein grafts. J Am Coll Cardiol. 2001;38(3):659-65.
• 8. Ellis SG, Brener SJ, DeLuca S, Tuzcu EM, Raymond RE, Whitlow PL, et al. Late myocardial ischemic events after saphenous vein graft intervention: importance of initially "nonsignificant" vein graft lesions. Am J Cardiol. 1997;79(11):1460-4.
• 9. Hakeem A, Helmy T, Munsif S, Bhatti S, Mazraeshahi R, Cilingiroglu M, et al. Safety and efficacy of drug eluting stents compared with bare metal stents for saphenous vein graft interventions: a comprehensive meta-analysis of randomized trials and observational studies comprising 7,994 patients. Catheter Cardiovasc Interv. 2011;77(3):343-55.
• 10. Vermeersch P, Agostoni P, Verheye S, Van den Heuvel P, Convens C, Van den Branden F, et al.; DELAYED RRISC (Death and Events at Long-term follow-up Analysis: Extended Duration of the Reduction of Restenosis in Saphenous vein grafts with Cypher stent) Investigators. Increased late mortality after sirolimus-eluting stents versus bare-metal stents in diseased saphenous vein grafts: results from the randomized DELAYED RRISC Trial. J Am Coll Cardiol. 2007;50(3):261-7.
• 11. Collet CA, Costa Jr. JR, Sousa AGMR, Feres F, Moreira A, Costa R, et al. Stents farmacológicos vs. stents convencionais no tratamento de enxertos de veia safena. Rev Bras Cardiol Invasiva. 2011;19(2):122-30.
• 12. Lee MS, Yang T, Kandzari DE, Tobis JM, Liao H, Mahmud E. Comparison by meta-analysis of drug-eluting stents and bare metal stents for saphenous vein graft intervention. Am J Cardiol. 2010;105(8):1076-82.
• 13. Mehilli J. Is drug-eluting stenting associated with improved results in coronary artery bypass grafts? Presented at: American College of Cardiology Scientific Session/i2 Summit; April 4, 2011; New Orleans, LA. New Orleans: ACC; 2011.

Stenting of saphenous vein grafts with drug eluting stents - maybe not as good as in native vessels

Stephen G. Ellis^I; Henrique B. Ribeiro^II

Publication Dates

• Publication in this collection
  03 Aug 2012
• Date of issue
  June 2011