Dual Protection May Boost Renal Stenting Outcomes

BY BRUCE JANCIN

NEW ORLEANS -- The key to preserving kidney function following renal artery stenting appears to be utilizing the dual protection provided by an embolic filter device plus the glycoprotein IIb/IIIa inhibitor abciximab, Dr. Christopher J. Cooper reported at a conference sponsored by the American College of Cardiology and the Society for Cardiovascular Angiography and Interventions.

This was the principal finding of the RESIST (Randomized Comparison of Safety and Efficacy of Renal Stenting) trial, a seven-center, prospective study in which 100 U.S. patients undergoing stenting to treat renal artery stenosis received either the platelet inhibitor abciximab (ReoPro) or placebo, and off-label use of the AngioGuard embolic protection device or not.

The primary end point was change in glomerular filtration rate (GFR) from baseline to 1 month, a follow-up period deemed long enough to permit resolution of any adverse renal effects of the contrast agent but short enough to avoid confounding effects of restenosis. The GFR declined by 10% in the control group, by 12% in those with AngioGuard only, and by 10% with abciximab only. In contrast, GFR rose by a highly significant 9% in the group given both AngioGuard and abciximab, said Dr. Cooper, chief the division of cardiovascular medicine, University of Toledo (Ohio).

The second major finding in RESIST was that platelet-rich thromboemboli were found in the filters much more commonly than anticipated, and abciximab sharply curbed this phenomenon. In the AngioGuard-only group, 42% of patients--compared with 7% of those on abciximab--had this gunk in their filters, he said. Levels of soluble CD40, a surrogate measure of platelet activation, dropped sharply with abciximab and remained low for 24 hours after.

"The thing that was really quite intriguing about the study was the unexpected observation of this rather remarkable incidence of platelet-rich thrombi landing in these filters. Certainly I have never viewed renal artery lesions as being particularly thrombogenic, nor have I viewed renal artery intervention as being fraught with platelet-mediated events," the cardiologist said. "Platelet aggregation is an issue we may not have been paying enough attention to. We may need to take a step back with regard to these embolic protection devices and give more thought to their potential interactions with platelets."

Atherosclerotic renal artery stenosis is one of the most common causes of secondary hypertension. Stenting is widely used in affected patients in an effort to improve blood pressure control while enhancing or preserving kidney function. Controversy surrounds the intervention, however, because registry studies show the roughly 25% rate of improvement in GFR is offset by a 20% incidence of deterioration in GFR post stenting. Failure to consider platelet aggregation and emboli may be the explanation for these suboptimal results, he said.

RESIST used the Cordis Corp.'s Genesis transhepatic biliary stent. It's an off-label application, but Dr. Cooper estimated that the stent is employed in 60%-80% of renal artery cases in the United States.

Dr. Cooper said in an interview that although he hasn't utilized glycoprotein IIb/IIIa inhibitor therapy in his renal artery-stenting cases, he plans to reconsider as a result of RESIST. Dr. Cooper said RESIST has changed his practice. He now uses both abciximab and an embolic protection device in high-risk patients.

Research funding for RESIST was provided by Cordis and Centocor Inc.

When asked to comment on this article, Dr. Frank Pomposelli, chief of vascular and endovascular surgery, Beth Israel Deaconess Medical Center, Boston, Mass., stated: "The results are certainly provocative and suggest that using the additional protective measures of an embolic protection device and a G2B3A inhibitor against platelet micro emboli could reduce the relatively common occurrence of loss of GFR when performing renal stenting. It's important to remember that renal stenting is performed by widely varying techniques. Whether the variation in technique in addition to patient selection might be as important as the phenomena noted in this trial for this problem is unknown. A larger prospective trial will be required to know if the added expense and potential increase of bleeding complications is justified by these results." Dr. Pomposelli is an associate medical editor for VASCULAR SPECIALIST