By Jeffrey Zimmet, MD, PhD
Associate Professor of Medicine, University of California, San Francisco; Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center
Dr. Zimmet reports no financial relationships relevant to this field of study.
SYNOPSIS: The two largest randomized trials to date have shown no advantage to drug-eluting stents compared to bare-metal stents in saphenous vein graft percutaneous interventions.
SOURCE: Colleran R, Kufner S, Mehilli J, et al. Efficacy over time with drug-eluting stents in saphenous vein graft lesions. J Am Coll Cardiol 2018;71:1973-1982.
In treatment of obstructive disease involving saphenous vein grafts (SVGs), percutaneous intervention (PCI) is a common element of management, with high rates of upfront technical success. Generally, drug-eluting stents (DES) perform better than bare-metal stents (BMS) in native coronary vessels, with lower rates of target vessel revascularization and higher rates of primary patency in complex lesions. Multiple studies comparing BMS with DES in SVGs have been performed, with the majority comprised of relatively small populations. The authors of most of those older trials have reported an advantage to DES in terms of short- and intermediate-term events. Based on those results, current guidelines in both the United States and Europe recommend DES as a first-line option for SVG lesions.
The largest of these studies is the ISAR-CABG trial, which enrolled 610 patients who were randomized to treatment with DES (303) or BMS (307). In 2011, the 12-month results from this trial were published. Major adverse cardiac events (MACE) at one year were significantly lower in the DES group compared with BMS (15.0% vs. 22.1%; relative risk, 0.64; P = 0.02), a difference that was driven almost entirely by a reduction in ischemia-driven target lesion revascularization (TLR) (6.8% vs. 13.1%; P = 0.01). There were no differences in death (5.1% vs. 4.7%; P = 0.83), myocardial infarction (MI; 4.2% vs. 6.0%; P = 0.27), or stent thrombosis (0.7% vs. 0.7%; P = 0.99).
Recently, investigators reported five-year outcomes from this trial. In the final analysis, the combined endpoint of death, MI, or TLR occurred in 159 patients in the DES group vs. 157 patients in the BMS group. While the event rate was lower in the DES group at the end of the first year, there was a “catch up” phenomenon over the subsequent time in the study, such that TLR actually was higher in the DES group after the first year, and not significantly different at five years.
The authors concluded that in patients undergoing PCI for treatment of SVG lesions, the initial advantage of DES over BMS is subsequently lost, such that there is no significant difference in efficacy by five years.
The first learning point from this trial is the obvious one — namely, that BMS can be used in vein grafts with similar efficacy to DES. In support of this finding, the recently published DIVA study showed no significant difference in outcomes between DES and BMS among 597 patients followed for a median of 2.7 years.1 The main implication of this result pertains to cost, as there remains a significant (although shrinking as the cost of DES comes down) price differential between these devices. One should not be too quick to conclude that a shorter length of dual antiplatelet therapy (DAPT) also is indicated, however, as all patients in the ISAR CABG trial were prescribed six months of DAPT, regardless of stent type.
What else can we learn from these data? We know that SVGs, compared with native coronaries, exhibit different pathophysiology, leading to higher rates of adverse outcomes. Additional lesions often form after treatment of an initial SVG stenosis, leading to recurrent SVG failure. In this regard, the numbers reported in the trial still are striking. At the five-year mark, the primary outcome (a composite of death, MI, and TLR) had occurred in more than half of all patients in the trial, regardless of treatment strategy. This sobering statistic reminds us that SVG failure, even after successful PCI, is a marker for adverse outcomes in a majority of patients, and should prompt us to optimize therapy in every possible way.
One strategy for dealing with this dismal record is to examine each individual case for the optimal revascularization strategy. Redo CABG often is not the best choice, but should be considered when the left internal thoracic artery has not been grafted, and when multiple lesions require treatment. Because PCI of the native coronary vessels is likely to demonstrate superior longevity to treatment of the graft, native vessel alternatives to SVG PCI also should be examined. For situations in which PCI of the native coronary is not overly complex, some authors have advocated approaching the native vessel first, even when PCI of the graft also is straightforward.
The two largest trials to date have shown no advantage of DES compared with BMS in PCI of SVG lesions. The high subsequent event rates in patients with SVG lesions should, in each case, prompt a global evaluation of optimal medical therapy and revascularization strategies.
- Brilakis ES, Edson R, Bhatt DL, et al. Drug-eluting stents versus bare-metal stents in saphenous vein grafts: A double-blind, randomised trial. Lancet 2018;391:1997-2007.