Sirolimus Stent Differences Come Down to 'Elution Kinetics' in PANDA Trial

Deborah Brauser

October 15, 2015

SAN FRANCISCO, CA — Two biodegradable sirolimus-eluting stents (SES) with differing elution and polymer-absorption rates provide similar clinical outcomes but differing rates of stent thrombosis after PCI, according to a new study presented here at TCT 2015[1].

The randomized, multicenter PANDA III trial of more than 2000 patients in China showed that the BuMA polymer-based SES (Sinomed) was noninferior to the Excel SES (Biomatrix) for target lesion failure after 1 year.This primary end point was defined as a composite of target vessel MI, cardiac death, or ischemia-driven target lesion revascularization—and affected 6.4% of each stent group (P for noninferiority=0.0003).

Although the BuMA group had a lower rate of stent thrombosis (P=0.047), none of the other secondary end points differed significantly between the two stent-treated groups.

Dr Bo Xu

Co–principal investigator Dr Bo Xu (Fu Wai Hospital, Beijing, China) noted at a press briefing that BuMA completely elutes sirolimus within 30 days and completely absorbs its polymer within 3 months — vs eluting and absorption rates of 180 days and 6 to 9 months, respectively, for the Excel SES.

"This is the kind of all-comers trial we like to see," session discussant Dr David J Cohen (Saint Luke's Mid America Heart Institute, Kansas City, MO) told attendees. "However, the challenge for practitioners in the United States is that we don't have either of these two stents available. It doesn't have any immediate clinical implications for us, but it does shed some light."

PANDA Trial Series

Xu noted that the BuMA has "a unique design incorporating an electrografting base layer between the polymer and stent strut, securing adhesion of the [poly-lactic-co-glycolic acid] PLGA coating."

The original 224-patient PANDA I trial compared those who received a BuMA SES with those who received an Endeavor drug-eluting stent (Medtronic). PANDA II is an ongoing registry study of 2500 Chinese patients to assess the BuMA in a real-world setting.

For PANDA III, the investigators wanted to compare the BuMA and Excel SES, a comparison they examined previously in the BuMA-OCT randomized trial of 80 patients. The primary end point for the earlier trial was stent strut coverage, as measured with optical computed tomography (OCT) at 3 months, and showed superiority for the BuMA SES.

Although both that stent and the Excel use a stainless-steel platform from which to elute sirolimus, the researchers sought to make "more specific and controlled comparisons of the direct effects of polymer and elution kinetics upon clinical outcomes," reported Xu.

Between December 2013 and August 2014, the investigators enrolled 2348 patients at 46 centers; half were randomly assigned to receive a BuMA SES and the other half received an Excel SES. All had symptomatic CAD, silent ischemia, or ACS.

In addition to having almost identical target lesion failure rates at 1-year follow-up (difference 0.1%), the stent groups had no significant differences in the individual components of cardiac death (1.2% vs 1.3%), target vessel MI (4.3% vs 4.9%), and ischemia-driven target lesion revascularization (1.9% vs 1.2%).

However, 0.5% of the BuMA SES group and 1.3% of the Excel group had definite or probable stent thrombosis within a year.

Elution Kinetics

After the presentation, discussant Cohen voiced some skepticism about the lower stent-thrombosis rate found. "This was the only difference that we saw, and it was a secondary end point that was somewhat borderline in the intention-to-treat population," he said. "I think this has to at least be taken with a word of caution."

However, codiscussant Dr Marco Valgimigli (Inselspital, Bern Switzerland) told heartwire from Medscape that an important study point is that the elution kinetics for this stent has now been investigated for a second time.

"We're always comparing one stent vs the other, meaning a completely different stent platform, completely different drugs, and completely different polymers," said Valgimigli. "The beauty of this study was that it focused on how the same drug was eluted from almost-identical stents, just with different polymer that released the drug over time," he said.

"The key take-home message is that the quicker the elution of the drug, the higher the proportion of stent that gets covered early on after dilution."

In addition, Valgimigli noted that there are clinical implications, because "if you can cover the stent properly, the stent-thrombosis risk is much lower and so the stent is safer. This study is important from a mechanistic standpoint."

After Xu's presentation at a late-breaking clinical-trials session, moderator Dr Gregg Stone (New York-Presbyterian Hospital/Columbia University Medical Center) noted that several of the top studies presented at TCT this year were from Asia. "Important research is being done outside of the Western European and United States access," he said.

Stone also complimented the large number of patients enrolled in this study and echoed some of Valgimigli's comments. "By far the most fascinating aspect of this, which looked at two very good stents, was the difference in stent thrombosis," he said.

"We saw that less strut coverage, as shown in OCT studies done previously, was associated with a greater rate of stent thrombosis. That's an important linkage, although we can't prove causation."

The study was funded by a research grant from SinoMed. Xu reported no relevant financial relationships.


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