More Bad News For The Once Promising Bioresorbable Stent

March 31, 2017 by Leave a Comment

(Updated)

–Problems for the Absorb BVS stent just won’t disappear

Bad news for the Absorb BVS stent continues to accumulate, though defenders of the device keep looking for a silver lining.

When it was approved in the US last summer the novel device appeared to have a bright future, with many prominent interventional cardiologists predicting it would quickly become a major force in the marketplace. Hiram Bezerra (UH Harrington Heart and Vascular Institute) told TCTMD that 60-70% of PCI cases might be eligible for Absorb, while Cindy Grines (Northwell Health) told MedPage Today that she expected to use the device in about half of her cases. But even then there were many less enthusiastic observers who were worried about the device.”

No one is making enthusiastic claims now, though there’s still an awful lot of excuses being generated by some of Absorb’s supporters.

Serious questions about the device emerged in the fall with the 3-year results from the ABSORB II trial, which failed to demonstrate the theoretical advantages of the stent and, even more troubling, uncovered a significantly higher rate of target vessel MI. Then the alarms grew louder when two more pieces of bad news came out at the recent American College of Cardiology meeting. First the 2-year results from the pivotal ABSORB III trial confirmed the fears raised in the fall, showing a significant increase in target lesion failure. Then the FDA weighed in, announcing that it was investigating the stent, confirming the broad concerns emerging from the trials.

Now this week more fuel was added to the fire. Results from yet another important randomized trial added fresh evidence against the stent. The AIDA trial was terminated early by the data and safety monitoring board when it became clear that the stent underperformed, failing to deliver better long term outcomes and instead confirming fears of increased stent thrombosis, including late stent thrombosis.

Defenders of the Faith

Once again industry-friendly interventional cardiology leaders have taken on the task of defending a device that has not lived up to its earlier great expectations.

As an example, in the face of the bad news at the ACC Roxana Mehran (Mount Sinai Hospital) put the best possible spin on the findings. She told MedPage Today: “We are somewhat comforted to see that the event rates are not extremely high as others had been thinking about. However, it is important for us to focus on the fact that this is breakthrough technology, and that we are waiting for the promise of the future superiority of this device to the current best-available metallic DES; that is really what physicians, patients, and everyone is looking for. I think we’re going to have to wait a long time after listening to this talk to actually find that. And the question is, what do we do here and now given what we have seen in ABSORB III 2-year data showing clearly an inferior result.”

Mehran, the designated discussion at the ACC late-breaking session for Absorb III trial, did not tell her audience of cardiologists to avoid use of the device. Instead, as Crystal Phend reported, “she suggested that until the scaffold is completely gone at 3 years, patients might need to remain on dual antiplatelet therapy (DAPT).

Mehran and others argue that the Absorb stent requires special implantation techniques. Since the bad news emerged the interventional community has developed a more rigorous protocol— called PSP— to aggressively prep the lesion, size the lesion, and post-dilate the stent. But the advantages of this technique have not been proven, and clearly increase the time and expense of the procedure when compared to a standard metallic stent.

A similar forgiving approach was adopted by Gregg Stone (Columbia University), who was the principal investigator of the Absorb III trial. In response to the AIDA trial he tweeted that the “nearly identical 2-year TVF rates… is encouraging [emphasis added].” But he dismissed the really frightening finding of increased stent thrombosis, which he said “can be reduced with better technique not practiced in this study.” Stone also said on Twitter that 3-years of prolonged DAPT “does make sense.”

Absorbing Criticism

In their efforts to minimize Absorb’s problems the defenders fail to offer any positive reason to actually use the device. For instance, although the stent thrombosis problem can likely be addressed with prolonged dual antiplatelet therapy, it’s hard to spin this as a positive response. “The bioresorbable scaffold should be used only in patients who can adhere to dual antiplatelet therapy for an extended period, possibly up to 3 years, without unacceptable side effects,” writes Debabrata Mukherjee (Texas Tech University Health Sciences Center), in a NEJM editorial on AIDA. But this is hardly a good thing, he notes: “The extended duration of dual antiplatelet therapy will come at the cost of a higher risk of bleeding, which will further attenuate any potential longer-term benefits of currently available bioresorbable scaffolds.” Stone even acknowledged in his tweet that he had found no evidence “whatsoever” to support prolonged DAPT, despite efforts to find such evidence. “Trust me I’ve looked [for the evidence],” he tweeted.

Similarly, the PSP technique has not been rigorously tested in a clinical trial, and it is certainly possible that all the best technique in the world may not make up for the deficiencies of an inferior device. In fact, the AIDA investigators told TCTMD that PSP began to be adopted during the course of the trial. “We have done some subanalyses and found that implantation technique does not really seem to influence the outcomes in AIDA… we still see clinical events in patients that underwent postdilatation.”

In addition to the added cost and bleeding risk of prolonged DAPT, PSP also increases both the cost and length of the procedure. The use of IVUS or OCT to ensure optimal stent placement is not a part of routine stent procedures.

“Given the lack of an advantage with respect to clinical efficacy, the challenges in delivering the device (including longer procedural times), and the higher rate of device thrombosis with the bioresorbable scaffold, there is little justification for routine use of the everolimus-eluting bioresorbable scaffold over the everolimus-eluting metallic stent,” writes Mukherjee.

On Twitter, Jonathan Reiner (George Washington University) went one step further: “Trial after trial finds worse outcomes for Absorb. Abbott should pull it from the market. No longer any justification to implant this stent.”

Update 1:

Sanjay Kaul (Cedars-Sinai) sent the following comment in response to the story:

Noninferiority business is monkey business! Accepting any degree of inferiority of the bioresorbable scaffolds is untenable given lack of any ancillary advantage in terms of safety, convenience or cost. In light of the emerging data from ABSORB II and III trials and AIDA, a rational reason to offer this device to our patients escapes me.

The CDRH/FDA clearly missed a trick in approving the device even in light of unfavorable benefit-risk balance in ABSORB III. Shifting the burden of proof to post-approval studies is not wise in my opinion. The key issue now is whether the FDA thinks there is sufficient adverse data to revoke the approval (offering a warning is not enough!). The ABSORB story should serve as an exemplar of why we (and the FDA) should not allow enthusiasm to get ahead of the evidence.

Update 2:

Abbott sent the following statement:

Enrollment in AIDA was completed in an era where the optimal deployment techniques were not well understood. While post-dilatation was performed in 26 of the 31 cases of stent thrombosis, the post-dilatation pressures used were below the current recommendation of >16ATM. More recent studies with contemporary deployment technique with post-dilatation pressures at 18-20 ATM are showing much lower rates of  stent thrombosis. It is also noted that the reported reference vessel diameter for the stent thrombosis cases was based only on visual estimation. We look forward to results of a more contemporary study (ABSORB IV) that is most reflective of current implantation techniques. 

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