BIOSOLVE-1 Shows Improvement in Paclitaxel-Eluting Bioabsorbable Stent

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Key Points:
  • Bioabsorbable drug-eluting stent has 100% procedural, device success in first-in-man trial
  • Rate of target lesion failure (7%) similar to current DES, earlier bioabsorbable platform
  • Late lumen loss greater than with alternative devices

By Michael Armstrong
Monday, March 18, 2013

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A fully bioabsorbable drug-eluting stent (DES) shows improvements over its predecessor and competitive levels of target lesion failure (TLF) at 1 year, according to results published in the March 9, 2013, issue of the Lancet. The metallic scaffold, however, still shows greater late lumen loss than with conventional DES and another bioabsorbable stent that are currently on the market.

Findings from the BIOSOLVE-1 trial were previously presented at EuroPCR 2012 in Paris, France.

BIOSOLVE-1, conducted by Michael Haude, MD, of the Lukas Hospital (Neuss, Germany) and colleagues is a prospective, non-randomized, multicenter, first-in-man trial testing the DREAMS (DRug-Eluting Absorbable Metal Scaffold; Biotronik, Bülach, Switzerland) in 46 patients with de novo coronary artery lesions (n = 47). DREAMS is a paclitaxel-eluting scaffold made of a magnesium alloy designed to be fully absorbed by the body in 9 to 12 months and coated with polylactic-coglycolic acid to control paclitaxel release.

Despite Safety, Lumen Decreases

All devices were implanted successfully. At 12 months, 3 of 43 patients with available follow-up (7%) had experienced the primary endpoint of target lesion failure (TLF; cardiac death, target-vessel MI, or clinically driven TLR) with no cases of cardiac death and no scaffold thrombosis. The events included 2 TLRs at 6 months and 1 periprocedural target-vessel MI during angiography at 12 months.

Angiography showed an in-segment acute gain of 1.13 mm immediately after the procedure. There were signs of a possible increase in minimum lumen diameter and decrease in late lumen loss between 6 and 12 months, but the differences did not reach statistical significance (table 1).

Table 1. Mean Angiographic Findings: In-Segment

 

After Procedure
(n = 47)

6 Months
(n = 36)

12 Months
(n = 34)

P Valuea

Minimum Lumen Diameter, mm

2.34

1.84

1.96

0.0001

Diameter Stenosis

15.21%

29.02%

25.31%

< 0.0001

Binary Restenosis

19%

9%

NS

Late Lumen Loss, mm

0.52

0.39

NS

a Post-procedure vs. 12 months.

Serial IVUS data were available only for 21 patients due to the study design and inconsistent pullback. IVUS findings showed a gradual decrease in scaffold area along with an increase in neointimal hyperplasia, such that lumen area decreased over time (table 2).

Table 2. Mean Paired Grayscale IVUS Findings: Per Lesion

 

After Procedure
(n = 21)

6 Months
(n = 21)

12 Months
(n = 21)

P Valuea

Scaffold Area, mm2

7.29

6.49

6.40

0.0218

Neointimal Hyperplasia Area, mm2

0

0.30

0.40

< 0.0001

Mean Lumen Area, mm2

7.31

6.19

6.02

0.0008

Minimum Lumen Area, mm2

6.36

4.69

4.42

< 0.0001

a Postprocedure vs. 12 months.

According to the paper, DREAMS offers an upgrade over its precursor, an absorbable BMS consisting of magnesium from the PROGRESS-AMS trial, and shows competitive rates of TLF in comparison with contemporary DES and a bioabsorbable everolimus-eluting stent (ABSORB BVS; Abbott Vascular, Santa Clara, CA). “However, DREAMS does not match the excellent late lumen loss results of these other devices,” Dr. Haude and colleagues write.

Concept Retains Interest

Although the long-term angiographic results for DREAMS may not be quite as good as some of its competitors, there is interest in the concept of an absorbable metallic scaffold.

Juan F. Granada, MD, of the CRF Skirball Research Center (Orangeburg, NY), told TCTMD in a telephone interview that a limitation of “bioresorbable polymer-based scaffolds is the need to have a relatively thick strut structure in order to maintain the architecture and mechanical strength that metals have. What makes this concept intriguing is that you can have the biomechanics of a metallic scaffold, but with complete reabsorption over time.”

In an e-mail communication with TCTMD, David E. Kandzari, MD, of the Piedmont Heart Institute (Atlanta, GA), also noted that "metallic-based platforms may have a particular advantage related to structural integrity and ability to expand beyond nominal size without compromising structural scaffolding properties."

The study authors also pointed to the high rate of strut apposition with DREAMS as evidence of the device’s “conformability.” Although serial optical coherence tomography data were only available for 7 patients, strut apposition went from 95.9% postprocedure, to 97.2% at 6 months and 99.8% at 12 months.

Changes Coming with DREAMS II

Both Drs. Granada and Kandzari suggested that part of the reason for the increased late lumen loss in BIOSOLVE-I may have been the choice of paclitaxel as opposed to a more effective limus-derivative for the antiproliferative drug.

Dr. Granada also pointed out that, with DREAMS, absorption of the polylactic-coglycolic acid (the polymer used to release the paclitaxel) happens after the paclitaxel is absorbed in the first 3 months. “When you have release [of the drug before] absorption of the polymer,” he said, “you may have a pro-inflammatory effect induced by the reabsorption process related to the polymer.”

In a telephone interview with TCTMD, Dr. Haude reported that both the anti-proliferative drug and the polymer will be changed for the DREAMS II stent.

DREAMS II will feature a poly-L-lactic acid polymer coating and sirolimus as the antiproliferative drug, as well as changes in architecture, composition, and strut thickness. BIOSOLVE-2, the study that will evaluate DREAMS II, should start in the second half of this year, Dr. Haude said. One-year safety and efficacy data should then be available by early 2015, with the goal of CE approval later that year.

Late Loss Not the Main Factor?

"Late lumen loss in absorbable scaffolds," Dr. Haude said, "is no longer, in my view, the parameter of choice." Because this technology is much more biologically active, progression may be different from what is seen with permanent DES, he said.

Dr. Haude stressed that “the patient doesn't care about his late lumen loss,” but rather about clinical outcomes.

Dr. Kandzari asserted that while there may be positive remodeling down the road, late lumen loss is still an important factor. “Whether it's permanent or bioabsorbable technology, the development of neointimal hyperplasia is, I believe, going to have an effect,” he noted.

According to Dr. Haude, the research group will be presenting 2-year data from BIOSOLVE-1 at EuroPCR 2013 in Paris. The trial is slated to have 3-year follow-up. Since DREAMS is absorbed quickly, he added, the 3-year results should give “the very final scenario.”

 


Source:
Haude M, Erbel R, Erne P, et al. Safety and performance of the drug-eluting absorbable metal scaffold (DREAMS) in patients with de-novo coronary lesions: 12 month results of the prospective, multicentre, first-in-man BIOSOLVE-I trial. Lancet. 2013;381;836-844.

Disclosures:

  • BIOSOLVE-I was funded by Biotronik.
  • Dr. Haude reports receiving grant research support and consulting fees from Biotronik.
  • Dr. Granada reports that the CRF Skirball Research Center has received research grants from several device companies actively working in the bioresorbable vascular scaffold field.
  • Dr. Kandzari reports serving as a consultant for Micell Technologies, which is developing a polymer-based bioabsorbable scaffold, and receiving consulting fees and grant support from Boston Scientific and Medtronic.

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