Comparing Drug-Eluting Stents to Bare-Metal Stents for Saphenous Vein Graft Lesion PCI

Percutaneous coronary interventions (PCI) in patients with prior coronary artery bypass graft (CABG) surgery constitute approximately 18% of PCI procedures performed in the United States.^1,2 The target vessel in a significant proportion of these cases (25%-35%) is a diseased saphenous vein graft (SVG), and SVG-PCI is associated with worse clinical outcomes as compared with native coronary artery PCI.^1-3 These adverse events include an elevated risk of distal embolization, no reflow, and periprocedural myocardial infarction (MI), and a substantially higher rate of target-vessel revascularization (TVR).⁴ Strategies to mitigate these risks have primarily involved use of embolic protection devices (EPDs) and drug-eluting stent (DES) implantation during SVG-PCI. While EPDs have reduced risk of periprocedural complications (distal embolization, no reflow, and MI), conclusive evidence for improved durability following SVG-PCI with DES remains controversial. This gap between the level of evidence and the use of DES during ~60% of SVG-PCIs in everyday clinical practice creates a fertile ground for meta-analytical studies that compile all available evidence.⁵ Thus, the systematic review and meta-analysis from Mosleh et al, which compares DES with bare-metal stent (BMS) for SVG-PCI, is relevant and timely.⁶

Perhaps the most important finding of this meta-analysis is that we simply do not have enough high-quality data to reliably answer the question at hand. Only three randomized controlled trials (RCTs)^7-9 and one post hoc analysis of an RCT¹⁰ have been published to date, all of which used first-generation DES implantation and provided inconclusive combined results (odds ratio for major adverse cardiac events was 0.53; P=.20). Although the 35 observational studies collectively suggest that DES implantation is beneficial,⁶ they are subject to marked selection bias. Prior meta-analyses of DES vs BMS have shown lower mortality with DES in observational studies with no difference in RCTs;¹¹ the benefit of DES has been limited to lower need for repeat target-lesion revascularization. Moreover, as the authors of this meta-analysis precisely point out, the DELAYED-RRISC trial remains an outlier. 

Can we expect new RCTs on DES vs BMS in SVGs? The BASKET-SAVAGE (Basel Kosten Effektivitäts Trial – SAphenous Venous Graft Angioplasty Using Glycoprotein 2b/3a Receptor Inhibitors and Drug-Eluting Stents) RCT (presented at the 2016 European Society of Cardiology meeting) randomized 173 patients undergoing SVG-PCI to Taxus DES vs BMS, but was terminated prematurely (planned enrollment was 240 patients). The incidence of major adverse cardiac events was significantly lower with DES as compared with BMS at 12 months (2.3% vs 17.9%; P<.001) and 3 years (12.4% vs 29.8%; P<.01), driven mainly by lower TVR with DES (19.1% vs 4.5% at 3 years). These are similar findings with those of the largest RCT performed to date, the ISAR-CABG (Is Drug-Eluting-Stenting Associated with Improved Results in Coronary Artery Bypass Grafts?”) trial, which also showed a significant reduction in TVR with DES implantation. BASKET-SAVAGE did not mandate angiographic follow-up, as was done in all prior RCTs; in addition, it was not blinded and used a first-generation DES (Taxus) that is no longer in clinical use.

The next (and probably the last) large RCT of DES vs BMS in SVGs is the DIVA (Drug-Eluting Stents vs Bare-Metal Stents In Saphenous Vein graft Angioplasty) trial (NCT 01121224). DIVA is a multicenter, Veterans Affairs cooperative trial that was designed to address the limitations of prior RCTs, ie, small sample size, routine angiographic follow-up, lack of blinding, low use of EPDs, and use of first-generation DES. The study has enrolled 599 patients and is currently in follow-up; results will be available in 2017.

Until then, most operators will likely continue to use DESs in SVGs, or preferentially treat the native coronary arteries,^1,3 an increasingly popular strategy given recent advances in the treatment of complex coronary lesions.¹²

References

1.    Brilakis ES, Rao SV, Banerjee S, et al. Percutaneous coronary intervention in native arteries versus bypass grafts in prior coronary artery bypass grafting patients a report from the national cardiovascular data registry. JACC Cardiovasc Interv. 2011;4:844-850.

2.    Brilakis ES, O’Donnell CI, Penny W, et al. Percutaneous coronary intervention in native coronary arteries versus bypass grafts in patients with prior coronary artery bypass graft surgery: insights from the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program. JACC Cardiovasc Interv. 2016;9:884-893.

3.    Brilakis ES, Banerjee S, Lombardi WL. Retrograde recanalization of native coronary artery chronic occlusions via acutely occluded vein grafts. Catheter Cardiovasc Interv. 2010;75:109-113.

4.    Brilakis ES, Lee M, Mehilli J, et al. Saphenous vein graft interventions. Curr Treat Options Cardiovasc Med. 2014;16:301.

5.    Aggarwal V, Stanislawski MA, Maddox TM, et al. Safety and effectiveness of drug-eluting versus bare-metal stents in saphenous vein bypass graft percutaneous coronary interventions: insights from the Veterans Affairs CART Program. J Am Coll Cardiol. 2014;64:1825-1836.

6.    Mosleh W, Gandhi S, El Siddig M, Schwalm JD, Farkouh ME. Comparison of drug-eluting stents to bare metal stents for PCI of saphenous vein graft lesions: systematic review and meta-analysis. J Invasive Cardiol. 2016;28:E139-E169. Epub 2016 Nov 15.

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;53:919-928.

8.    Vermeersch P, Agostoni P, Verheye S, et al. Randomized double-blind comparison of sirolimus-eluting stent versus bare-metal stent implantation in diseased saphenous vein grafts: six-month angiographic, intravascular ultrasound, and clinical follow-up of the RRISC trial. J Am Coll Cardiol. 2006;48:2423-2431.

9.    Mehilli J, Pache J, Abdel-Wahab M, et al. Drug-eluting versus bare-metal stents in saphenous vein graft lesions (ISAR-CABG): a randomised controlled superiority trial. Lancet. 2011;378:1071-1078.

10.    Jeger RV, Schneiter S, Kaiser C, et al. Drug-eluting stents compared with bare metal stents improve late outcome after saphenous vein graft but not after large native vessel interventions. Cardiology. 2009;112:49-55.

11.    Kirtane AJ, Gupta A, Iyengar S, et al. Safety and efficacy of drug-eluting and bare-metal stents: comprehensive meta-analysis of randomized trials and observational studies. Circulation. 2009;119:3198-3206.

12.    Kirtane AJ, Doshi D, Leon MB, et al. Treatment of higher-risk patients with an indication for revascularization: evolution within the field of contemporary percutaneous coronary intervention. Circulation. 2016;134:422-431.

From the ¹University of Texas Southwestern Medical Center, Dallas, Texas and Veterans Affairs Southwestern Medical Center, Dallas, Texas; and ²Minneapolis Heart Institute, Minneapolis, Minnesota.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Banerjee reports research grants from Gilead and the Medicines Company; consultant/speaker honoraria from Covidien and Medtronic; ownership in MDCare Global (spouse); intellectual property in HygeiaTel. Dr Brilakis reports research support from Boston Scientific and InfraRedx; consulting/speaker honoraria from Abbott Vascular, Asahi Intecc, Cardinal Health, Elsevier, and GE HealthCare; spouse is employee of Medtronic.  

Address for correspondence: Subhash Banerjee, MD, 4500 S. Lancaster Road (111a), Dallas, TX 75230. Email: subhash.banerjee@utsouthwestern.edu