RIO: Abciximab No Benefit for Peripheral Interventions

BY BRUCE JANCIN

VIENNA -- The addition of abciximab does not provide major benefit over standard dual-agent antiplatelet therapy in patients undergoing percutaneous intervention for femoropopliteal long chronic occlusions, Dr. Iris Baumgartner said at the annual congress of the European Society of Cardiology.

She presented preliminary 6-month outcomes of the ReoPro and Peripheral Arterial Intervention to Improve Clinical Outcome in Patients with Peripheral Arterial Disease (RIO) trial, a multicenter European study in which 423 such patients with TASC C and D lesions were randomized in double-blind fashion to placebo or a 0.25-mg/kg bolus of abciximab followed by a 12-hour maintenance infusion. All participants received aspirin at 100 mg/day and a 300-mg preprocedural loading dose of clopidogrel followed by 75 mg/day for 28 days.

"Although previous randomized controlled trials demonstrated the benefit of abciximab in patients undergoing angioplasty plus or minus stenting in acute or subacute limb ischemia, RIO failed to demonstrate superiority of abciximab over placebo to reduce the composite end point of death, amputation at any level, reinterventions, or reocclusion at 30 days in chronic long occlusions at the femoropopliteal site--and it was associated with significantly increased access site bleeding," reported Dr. Baumgartner of University Hospital, Bern, Switzerland.

The rate of the composite end point was 5.08% with abciximab and 5.64% with placebo. RIO organizers had expected the rate to be 20% or more in the placebo arm based upon studies conducted in an earlier era when neither stenting nor dual-antiplatelet therapy were routine.

The severe bleeding rate in RIO was 5.1% in the abciximab arm and 1.0% with placebo. None of the episodes was life threatening, intracranial, or required surgery. Most involved localized access site bleeding.

Although follow-up is planned to continue for 3 years, Dr. Baumgartner noted that abciximab has already demonstrated a significant advantage in terms of several shorter-term secondary end points. The angiographically confirmed distal embolization rate of 6.1% with the glycoprotein IIb/IIIa inhibitor was less than half that in the control group. Target vessel reocclusion at 6 months occurred in 22% of the abciximab group, compared with 39% of controls. Greater than 50% restenosis was demonstrated by duplex ultrasound in 56% of the abciximab group and 68% of controls. And abciximab-supported procedures averaged 31 minutes shorter duration than the 106 minutes in the control group.

But these secondary successes didn't sway RIO discussant, Dr. Horst Sievert, who said, "With the currently available information about the results of this trial, ReoPro seems to be not indicated in elective peripheral interventions." Dr. Sievert said he couldn't get past that sharply increased bleeding risk.

"There was a fivefold increase in major bleeding complications. Although none of the bleeding complications in this trial have been life threatening, you have to remember that bleeding complications--especially bleeding complications related to the access site--are the most important cause of mortality in peripheral interventions," said Dr. Sievert of the Cardiovascular Center, Frankfurt, Germany.

He speculated that abciximab's failure to significantly reduce the primary composite end point in RIO may have been due to a flawed study premise. While abciximab has shown impressive efficacy in coronary interventions, the thromboembolic complications which the drug addresses so effectively figure far less prominently in the setting of peripheral interventions.

"Acute dissections or thrombus formation later on may be more important than acute thrombus formation during the peripheral procedure or the first 24 hours afterwards," he observed.

RIO was supported by Eli Lilly.

Asked to comment on this article, Dr. James McKinsey stated: "This is an interesting study showing improved outcomes in short term goals of distal embolization, decreased reocclusion and restenosis rates but with a fivefold increase in groin hematoma rates. Certainly bleeding complications are always a concern with the use of a IIa/IIIb inhibitor.

"One issue that was not addressed in the article was the use of closure devices. The increased instance of groin hematoma could be reduced with the use of closure devices especially in the case where complex anticoagulation strategies are used." Dr. McKinsey is chief of vascular surgery at Columbia University Medical Center in New York, and an associate editor for VASCULAR SPECIALIST