乌鸦传媒

MIAMI -- In an effort to reduce the small but real risk of stent thrombosis associated with drug-eluting stents, stent makers have turned to devices whose polymer or scaffolding dissolves over time.

A series of studies reported at the Transcatheter Cardiovascular Therapeutics (TCT) meeting highlighted the latest results from bioabsorbable devices.

DESSOLVE II

The MiStent sirolimus-eluting biodegradable polymer stent (Micell Technologies) had a mean 0.27 mm late lumen loss at 9 months compared with 0.58 mm for the Endeavor zotarolimus-eluting durable polymer stent (Medtronic) (P<0.001 for superiority), according to David E. Kandzari, MD, of the Piedmont Heart Institute in Atlanta, and colleagues.

The DESSOLVE II trial, which randomized 184 patients in a 2:1 ratio favoring MiStent, also showed a MACE rate of 4.3% compared with 6.7% for Endeavor (P=0.49 for non-inferiority), as well as 0% definite/probable stent thrombosis and a 0.9% target lesion revascularization (TLR) rate compared with rates of 1.7% and 1.7%, respectively, for the Endeavor, Kandzari said.

"Stents with bio-permanent polymers are considered a stimulus for chronic inflammation and hypersensitivity reactions, incomplete re-endothelialization, and neo-atherosclerosis," Kandzari told 乌鸦传媒.

The MiStent polymer dissolves in 45 to 60 days, leaving a bare-metal stent behind, but the drug continues to suppress neointimal hyperplasia for a few more months, Kandzari said.

Many researchers use intravascular ultrasound (IVUS) and optical coherence tomography (OCT) to visualize finer details associated with biodegradable stents. Using these tools, Kandzari and colleagues found low and uniform neo-intimal hyperplasia distribution with 0.34% uncovered struts and no malapposition through 9 months.

In addition, rapid atrial pacing showed similar endothelial function at 9 months between the two stents, Kandzari reported.

BIOSOLVE I

In a smaller study called BIOSOLVE I (46 patients), Michael Haude, MD, of Städtisch Kliniken-Neuss in Germany, and colleagues found that a paclitaxel-eluting bioabsorbable magnesium scaffold called Dreams (Biotronik) had a 6- and 12-month late lumen loss of 0.64 and 0.52 mm, respectively.

An earlier bare-metal version of the dissolving stent had a 4-month late lumen loss of 1.08 mm, and a TLR rate of 26.7% versus 4.7% for Dreams, which is why researchers added the anti-proliferative drug and slowed the scaffold absorption in the second-generation stent.

At 24 months, 20 patients showed a 10% rate of target lesion failure and of TLR, as well as no cardiac deaths, MIs, or scaffold thrombosis.

ABSORB Series

Several researchers provided favorable updates of the various ABSORB studies, which are evaluating the Absorb Bioabsorbable Vascular Scaffold (BVS) from Abbott Vascular, the first such stent approved in Europe (2011).

Pieter Smits, MD, of Maasstad Ziekenhuis in Rotterdam, the Netherlands, and colleagues reported that at 3 years, the 44 patients in the first-in-man ABSORB cohort B1 (whose BVS was an improvement over the version used in ABSORB cohort A) had no cardiac deaths, a 2.3% rate of MI, 4.5% rate of ischemia driven TLR, no scaffold thrombosis, and no new MACE between 1 and 3 years.

Following on the positive clinical data from cohorts A and B, researchers then opened up enrollment for the ABSORB EXTEND trial.

Antonio L. Bartorelli, MD, of the University of Milan in Italy, reported that the first 250 patients (of an expected 1,000) had comparable rates of definite/probable stent thrombosis and MACE at 12 months compared with cohort B and also compared with historical controls from pooled SPIRIT population, where patients received the permanent Xience everolimus-eluting stent.

Bartorelli noted that patients in EXTEND are more high risk than those in cohort B.

Polymer-Free Stents

Ricardo A. Costa, MD, PhD, of Instituto Dante Pazzanese de Cardiologia in Sao Paulo, provided updates to attendees of TCT of the Amazonia PAX paclitaxel-eluting, polymer-free stent (Minvasys) studies.

The polymer-free stent elutes 98% of its drug at the site and is back to a bare stent in 45 days.

PAX-A, a 31-patient first-in-man trial found the Amazonia stent comparable to the Taxus Liberté (Boston Scientific), which has a permanent polymer, regarding late lumen loss, percent volume obstruction, and strut coverage at 4 months. At 24 months, neither stent had a stent thrombosis, and MACE and individual components of MACE were comparable.

The multicenter PAX-B registry, which comprises 103 patients, shows low rates of cardiac death (0%), MI (1%), TLR/TVR (25%), and stent thrombosis (0%), Costa reported.

Finally, the BI-PAX multicenter registry with 101 patients shows the NILE PAX bifurcated stent at 9 months to be associated with a 14% binary restenosis rate in the main branch, 13% in the side branch, and 18% in-bifurcation in the 87-patient per-protocol population.

At 2 years, there were no stent thromboses, a 15% rate of TLR and TVR, 1% rate of cardiac death, and 1% rate of non-Q wave MI.

More Than the Unseen Parts

These new-generation bioabsorbable stents have more going for them than their disappearing polymer or scaffold. Engineers are refining every aspect of these devices for optimal delivery, minimal acute injury, and very low to no late-term adverse events.

For example, the Mitsu polymer-free stent is an "ultra-thin" device (45 μm) that allows the "lowest possible vessel wall injury," according to Costa.

He also provided an update on the VESTAsync stent (MIV Therapeutics), which has a "3D microporous nanofilm hydroxyapatite" with a sirolimus elution curve that peaks at about 28 days and continues up to 45 days, Costa said.

The DESynd BD (Elixir Medical) elutes Novolimus over 4 weeks and the polymer degrades in 6 to 9 months. The cobalt chromium alloy is 81 μm thick, and the polymer coating is less than 3 μm thick.

New generation drug-eluting stent makers have combined alloys in various ways in an effort to make the perfect product. The ProKinetik and MultiLink 8 (Abbott) consists of 55% cobalt, 20% chromium, 15% tungsten, and 10% nickel. Compare that to the Integrity (Medtronic), which has 33% cobalt, 20% chromium, 35% nickel, 10% molybdenum, and 2% other. And the Omega from Boston Scientific has 37% iron, 33% platinum, 10% chromium, and 9% nickel, with some manganese and molybdenum thrown in.

Bioabsorbable stents also are using various alloys in the scaffolding such as cobalt, chromium, and magnesium. And researchers are arranging struts to optimize performance, such as having cells closer at the ends and more open in the middle (Mitsu, Meril Lifescience) or having polymer-free scaffolding with hollow drug-filled cores (Drug-Filled Stent, Medtronic).

Another novel technology is the Genous Combo stent (OrbusNeich) that has a pro-healing antibody covered surface that "captures" endothelial progenitor cells.

The bioabsorbable Orsiro (Biotronik) stent incorporates "passive stent coatings" like PROBIO, which "reduces the interaction between tissue and blood with the metallic surface of the stent," according to Stephan Windecker, MD, of the University of Bern in Switzerland. The BIOFLOW clinical program is testing this device.

The FIREHAWK stent (MicroPort Medical) has grooves in the outer surface of the stent that act like reservoirs to hold and release the sirolimus. It is being tested in the TARGET clinical program.

"In the end, researchers hope to design a device the could potentially accommodate more of the natural movements of the blood vessel, a device that is only used for a prescribed period of time and then goes away in a very safe manner. Such a device would be very useful," Thomas Tu, MD, of Louisville Cardiology in Louisville, Ky., told 乌鸦传媒.

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