ACC 2009: "Plaque Sealing" With DES in Saphenous Vein Grafts Prompts Both Accolades and Skepticism: VELETI

Shelley Wood

April 07, 2009

April 7, 2009 (Orlando, Florida) — Researchers have toyed for years with the idea of using drug-eluting stents (DES) or other strategies to "seal" coronary plaques before they progress significantly or rupture: now researchers testing the idea in saphenous vein grafts (SVGs) say that this is a reasonable strategy--at least in this particular setting, where atherosclerosis is markedly accelerated. Calling it a "proof-of-concept" study, researchers for the VELETI trial say their findings warrant further study in a larger group of patients, but only for saphenous vein grafts. At least one expert, however, called the strategy "absurd" and "criminal," suggesting that using DES prophylactically, for nonsignificant lesions, could create more problems than solutions.

Dr Josep Rodés-Cabau (Hôpital Laval, QC) presented the VELETI results last week during the American College of Cardiology (ACC) 2009 Scientific Sessions. "This first study evaluating the use of a mechanical strategy--coronary stenting--as a preventive treatment for saphenous vein graft atherosclerosis progression showed that sealing moderate nonsignificant lesions with paclitaxel-eluting stents was effective and safe for the prevention of SVG disease progression," he said. "The results of this pilot study suggest that a new preventive strategy may be further considered for the management of this challenging subset of post-CABG patients."

Holding Atherosclerosis at Bay

The VELETI study enrolled 57 patients, identified as having one or more "moderate" SVG lesions (30% to 60% stenosis) by angiography--in all cases, these moderate lesions were identified during angiography for another, more advanced, lesion that was producing clinical symptoms. On average, patients in the study were 12 years post-CABG. Patients were randomized to medical therapy or stent implantation, and then both groups underwent baseline intravascular ultrasound (IVUS) evaluation and subsequent angiography and IVUS again at 12 months.

At follow-up, change in minimal lumen diameter from baseline was significantly increased in the stent group but reduced in the medical-therapy group. Likewise, percent stenosis was reduced in the stent group but increased in the medical group, both to a statistically significant degree. A full 30% of patients had greater than 50% stenosis at follow-up in the medical group, compared with no patients in the stent group.

Minimal lumen area by IVUS, the primary end point for the study, was significantly reduced in the medical-therapy group and significantly increased in the DES group, and the differences between the two values, at follow-up, were also statistically significant. Atheroma volume in nondiseased segments, the primary safety end point of VELETI, showed no differences between the two groups. Major adverse cardiac events, a secondary end point of the study, were not statistically different between the two groups, although five patients in the medical-treatment group required revascularization procedures.

In his concluding remarks, Rodés-Cabau noted that the periprocedural complication rate was low (3%) and there were no cases of restenosis or stent thrombosis at 12 months. Moreover, plaque sealing appeared to have no effects on atherosclerosis progression in other segments.

VELETI: 12-Month Angiographic and IVUS Outcomes

End point Medical therapy DES p
Change in minimal lumen diameter (mm) -0.3 +0.94 <0.0001
Stenosis (%) +7 -23 <0.0001
Minimal lumen area (mm2) -0.7 2.5 0.001
Change in atheroma volume in nondiseased segments (%) 3 3.2 0.96

Some Concerns

Commenting on the study for heartwire , Dr Renu Virmani (CVPath Institute, Gaithersburg, MD), who has long raised concerns about the effects of DES on vessel healing, expressed considerable discomfort with the idea of using DES in asymptomatic, noncritical lesions, calling the strategy "unethical."

For one, investigators did not report the rate of periprocedural MI (by CK-MB or troponin) during their presentation, she notes. "How can you justify doing this, if you intervene in nonsignificant disease and you get a CK-MB rise?" she asked. She also pointed to the higher use of dual antiplatelet therapy in the DES-treated patients, compared with the medically treated patients, 93% vs 63%. "If you don't give the antiplatelet drugs equally, you can't compare the two," she said.

Lastly, she expressed concern about whether the change in minimal lumen area was truly atherosclerosis or whether it was just neointimal formation. "Neointima doesn't have the necrotic core, so it doesn't rupture, it doesn't cause thrombosis," she explained. "I'm not saying that patients 12 years after vein grafts don't have progression of disease; they do. But I don't know if that's really atherosclerosis you're treating," she said. While Virmani didn't rule out the notion of plaque sealing, she said that doing it with drug-eluting stents was not the way forward, given the "raw" surface these create on the vessel wall. "I think that's just criminal," she said.

In response, Rodés-Cabau clarified that periprocedural MIs, defined as a CK-MB three times the upper limit of normal, occurred in just one patient in the stent group--hence, the 3% mentioned in his concluding statements. Moreover, IVUS confirmed that disease progression was, indeed, atherosclerosis, he said--plaque burden in the medically treated group increased from 61% to 68%, he noted.

As for Virmani's concerns about a differential effect of clopidogrel, Rodés-Cabau acknowledged: "We cannot completely exclude a potential influence of Plavix therapy on the final results." That said, he continued, secondary analyses found no interaction between clopidogrel therapy and significant atherosclerosis progression.

Investigators are now planning a larger study, with clinical end points, he told reporters.

Only in SVG Lesions, Investigators Stressed

Asked by heartwire , during an ACC press conference, about the appetite for extending indications for DES to yet another subset of patients--in this case, patients with lesions that ordinarily would not meet criteria for stenting, Rodés-Cabau emphasized that "moving to other types of lesions--for example, in native CAD--that is not at all the type of strategy we are talking about here."

Backing him up, Dr Claudio D Schuger (Henry Ford Hospital, Detroit, MI), who moderated the press conference, called VELETI a "fascinating" and novel study. "This strategy for proceeding [with stenting] refers only to saphenous vein grafts,” he emphasized. "Here, there is a very specific progression that appears to be accelerated rapidly and inevitably. The strategy of plaque sealing appears to be warranted, because the outcome [for moderate lesions left untreated] is always predictable."

Of note, the concept of plaque sealing has been tested in other settings with disappointing results. The DEFER study, presented at the European Society of Cardiology 2005 Congress and testing the use of "plaque sealing" with stents in intermediate, de novo coronary stenosis but no inducible ischemia, showed that the strategy had no impact on event rates over five years.

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