Stenting of Saphenous Vein Grafts — A Treacherous Road to Travel

Following the first successful clinical aorto-coronary saphenous vein graft (SVG) implantation by DeBakey and Garrett in 1964,¹ coronary artery bypass grafting (CABG) rapidly became the most frequent surgical procedure in the United States in the 1970s. This explosive growth lasted for nearly two decades and three prospective, randomized, multicenter trials were performed demonstrating a survival advantage in patients with left main and triple coronary artery disease (CAD).^2–4 By the mid 1980s, Floyd Loop at the Cleveland Clinic developed the Internal Mammary Artery (IMA) as an arterial graft to bypass the left anterior descending artery (LAD) and demonstrated its potent survival benefit.⁵ However, patients with multivessel CAD undergoing CABG still required the 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.^6,7 In the early 1980s, the emergence of percutaneous coronary intervention (PCI) offered a less invasive revascularization alternative for native coronary arteries to CABG, particularly for patients with less extensive obstructive CAD. By 1990, more patients underwent PCI than CABG,⁸ and over the last decade, this trend has continued in the United States.⁹

Percutaneous coronary intervention has also become an attractive approach in patients with severe SVG disease with patent LIMA grafts in whom redo-CABG is associated with higher mortality and increased risk of complications. Indeed, most patients with SVG disease requiring revascularization undergo PCI either of the bypassed native vessel or more commonly of the SVG, as the native vessel is often occluded. Clinical and pathological studies have demonstrated that atherosclerosis in SVGs represents friable bulky disease that makes SVG PCI fraught with the immediate hazards of distal embolization and no reflow and delayed risk of high rates of restenosis.^10–13 Compared to balloon angioplasty, bare metal stenting of SVGs yielded lower mortality, myocardial infarction risk, freedom from emergency surgery and target lesion revascularization.¹⁴ A significant advance in SVG PCI was the advent of proximal and distal protection devices, which dramatically reduced distal embolization, no-reflow, and subsequent peri-procedural complication rates.^15–17

To address the longer term complication of high rates of restenosis with bare metal stent (BMS) PCI of SVGs, drug-eluting stents (DES) were proposed as the solution.¹⁸ Despite initial optimism from the RRISC (Reduction of Restenosis In Saphenous vein grafts with Cypher) trial demonstrating improved restenosis, target lesion revascularization and target vessel revascularization rates in patients with sirolimus-eluting stents (SES)¹⁹ compared with BMS, long-term follow-up at a median of 32 months raised concerns that more patients died in the SES group compared to the BMS group (11 of 38 patients in the SES versus 0 of 37 patients in the BMS group, p<0.001).²⁰ In contrast to the RRISC study, the recently presented Efficacy Study of Drug-eluting and Bare Metal Stents in Bypass Graft Lesions (ISAR-CABG) results showed that at one-year follow up, the DES group had a 35% lower incidence of the primary composite end point (death, MI, and target lesion revascularization) than the BMS group (16.5% vs 22.1%, p=0.028). Not surprisingly, this difference was driven by the decrease in target lesion revascularization (7.2% vs 12.9%, p=0.020). There were no statistically significant differences in the individual rates of death or MI. Similarly, the Stenting of Saphenous Vein Grafts (SOS) trial, a small randomized trial of paclitaxel-eluting stent (PES) versus BMS for SVG PCI, demonstrated at a median follow-up of 35 months lower incidence of myocardial infarction (hazard ratio [HR]: 0.32, p = 0.01), target lesion revascularization (HR: 0.20, p = 0.004), target vessel revascularization (HR: 0.41, p = 0.03), and target vessel failure (HR: 0.34, p = 0.001) as well as a trend toward less definite or probable stent thrombosis (HR: 0.15, p = 0.08) in patients treated with PES compared with BMS, though all-cause mortality (HR: 2.04, p = 0.19) and cardiac mortality (HR: 0.62, p = 0.51) did not differ between groups.²¹

The article by Michael et al published in this issue of the Journal provides additional insights into these promising results with PCI of SVGs using DES by performing a post-hoc analysis of recurrent events after the initial major adverse cardiac event (MACE).²² The rationale for performing this analysis is that most studies, including the original SOS study, only report the time to first MACE at which time patients were censored. Therefore, subsequent events (which are frequent in patients with advanced SVG disease) are not evaluated and reported. The authors found that in total during a median follow-up of 35 months, the majority of patients, 52 of the 80 patients (65%), experienced at least one MACE. In 13 of 15 patients who died, death was the first event. Thirty-nine patients (49%) had at least one non-fatal event of whom a subsequent adverse event occurred in 14 patients (12 in BMS vs 2 in PES group; p=0.24). Although the incidence of recurrent MACE related to the SVG appeared to be greater in the BMS cohort this was not a statistically significant finding in this small cohort. Another interesting observation of this analysis is that 11 of 26 (42%) subsequent MACE after an initial event were related to the same target SVG.

The authors make three conclusions from this analysis. First that patients undergoing SVG PCI who have a first adverse event have a high incidence of recurrent MACE that commonly manifest as an acute coronary syndrome; second that recurrent events are often related to the vein graft that was originally stented; and third that recurrent events are more likely to occur in patients who receive BMS than DES. While these observations which seem sensible may turn out to be accurate, 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. As data from the large ACC NCDR suggest, the higher risk of complications associated with PCI of SVGs may relate to the advanced age of these patients, the age of SVG graft and multiple comorbidities these patients possess.²³

Therefore, due to lack of firm consensus regarding the use of DES for PCI of SVGs, the current PCI guidelines including the 2009 focused update recommend that a DES should be considered as an alternative to the BMS in subsets of patients in whom trial data suggest efficacy (Class I, Level of Evidence: A) and that DES may be considered for use in anatomic settings in which their usefulness, effectiveness, and safety have not been fully documented in published trials (Class IIb, Level of Evidence: C).^24,25 While the pathobiology of accelerated atherosclerosis in SVGs may be distinct from native atherosclerosis, it seems logical to apply some of the same principles that are utilized in choosing DES versus BMS in native coronary arteries to SVG PCI, namely, to reach for DES for longer lesions that reside in smaller vessels. Clearly, intensification of medical therapy and risk factor modification remains paramount in this cohort with advanced atherosclerosis and comorbidities.

In summary, although PCI is often the preferred approach to revascularizing SVGs and the advent of stents and atheroembolic protection devices have improved outcomes, SVG PCI remains a complex and treacherous road to travel.

References

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From Emory University, Atlanta, Georgia.
The authors report no conflicts of interest regarding the content herein.
Address for correspondence: Habib Samady, Professor of Medicine, Emory University, 1364 Clifton Road, Suite F606, Atlanta, Georgia 30322. Email: hsamady@emory.edu