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Page 10 of 14 Heng et al. Vessel Plus 2023;7:31 https://dx.doi.org/10.20517/2574-1209.2023.97

HUMAN CLINICAL TRIALS OF VEIN GRAFT FAILURE PREVENTION
Over the years, several therapies demonstrating promising preclinical data for the prevention of vein graft
failure have been implemented in clinical trials. However, translation from laboratory to human application
has produced mixed results, with some treatments demonstrating encouraging findings and others falling
short of anticipated outcomes.

PREVENT IV
The Project of Ex-vivo Vein Graft Engineering via transfection (PREVENT IV) trial was a phase III,
multicenter, randomized, double-blind, placebo-controlled trial that evaluated the efficacy and safety of
edifoligide, an E2F transcription factor decoy shown to reduce intimal hyperplasia in animal models, in
[45]
preventing vein graft failure following CABG . A total of 3,014 patients undergoing CABG with at least
two planned vein grafts were enrolled. The primary endpoint was the rate of vein graft failure at
12-18 months after enrollment. Both at 1- and 5-year follow-ups, edifoligide was found to be no more
effective than placebo in preventing vein graft failure, and did not affect outcomes or survival after
CABG [45,46] .

Extent study
The Extent study was a phase I randomized clinical trial that enrolled 20 patients undergoing isolated
CABG to evaluate the use of an external Dacron stent for the prevention of vein graft failure . The Extent
[47]
(Vascutek Ltd, Inchinnan, Scotland) was composed of an incomplete tube of macroporous knitted polyester
reinforced with PTFE ribs at 1 cm intervals to form a flange. On follow-up angiography between
6-18 months after CABG, 17 of 20 Extent grafts were thrombosed, while all LIMA and non-extent vein
grafts remained patent. The disappointing universal thrombosis of Extent vein grafts in this study was
attributed to stent rigidity and graft kinking resulting from the flanged edge design.

eSVS Mesh
The eSVS mesh (Kips Bay Medical Inc, Minneapolis, MN, USA) was an external graft stent comprised of a
knitted Nitinol mesh tube, and was advertised as being highly flexible and kink resistant. The procedure of
eSVS application in CABG involved selecting an appropriately sized device based on saphenous vein
measurement, pulling the SVG through the mesh tube, and finally fixing the mesh to the vein using fibrin
glue. As part of a prospective, randomized, multicenter trial, Schoettler et al. reported that among 25
subjects enrolled in their clinic, a nine-month follow-up demonstrated 27.8% patency of mesh-supported
grafts vs. 85.7% patency in conventional vein grafts . Inderbitzin et al. similarly reported 76% patency
[48]
of meshed SVGs at 1 year vs. 100% patency in non-meshed SVGs. Inferior patency in these studies
[49]
was believed to be related to the use of fibrin glue and stent undersizing .

VEST
Perhaps the most prominently studied in-human device for the prevention of vein graft failure has been the
VEST (Vascular Graft Solutions Ltd, Tel Aviv, Israel). The VEST device is an external sheath composed of
braided cobalt-chromium alloy that had demonstrated promise in animal models of CABG, and has since
been investigated in multiple randomized controlled trials. In the VEST I trial, 30 patients undergoing
CABG were enrolled to receive one external stent device to a single SVG randomly assigned to either the
right or circumflex coronary territory . At 1-year follow-up angiography, the primary endpoint of intimal
[50]
hyperplasia by mean wall area was significantly reduced (4.37 ± 1.40 mm vs. 5.12 ± 1.35 mm , P = 0.04) with
2
2
VEST application, while early graft failure was not significantly different between stented and non-stented
vein grafts (30% vs. 28.2%, P = 0.55). Additionally, SVG failure rates in both groups were noted to be
significantly lower in the left circumflex (17.6% vs. 27.5%, P = 0.02) as compared to the right coronary
territory (46.2% vs. 13.4%, P = 0.01), and this was suspected to be related to the use of metallic clips to ligate