A key prediction for interventional cardiology coming out of recent Transcatheter Cardiovascular Therapeutics (TCT) and American College of Cardiology (ACC) meetings is that bioresorbable stents will eventually replace conventional metallic stents in the coming years. Experts say dissolving stents have their drawbacks compared to metallic stents, but as the technology continues to advance, these issues may be resolved. Even if they are not, experts say growing clinical data shows the benefits of bioresorbable stents may outweigh any drawbacks.
Most bioresorbable stents are made of polylactic acid, a naturally dissolvable material that is used in medical implants such as dissolving sutures. The drawbacks of using polymer include recoil after expansion, stent thickness causing maneuverability and crossing issues, difficulty visualizing a non-metallic stent on fluoroscopy and stents not crimping firmly on delivery balloons.
However, the advantage is not implanting a permanent metal prosthesis. Since the stent disappears, it eliminates the cause of potential inflammation that can lead to late-stent thrombosis and restenosis. Once the stent dissolves after about two years, it restores the vessel to a natural state of vasoconstriction and vasodilatation. The disappearance of the device also leaves open all options if future interventions are needed.
There are at least 15 bioresorbable stent programs in progress, with five in the advanced development stages and two having received European CE mark approval, said Alexandre Abizaid, M.D., Ph.D., FACC, director of cardiology, Dante Pazzanese Hospital, Sao Paulo, Brazil, at ACC 2014. The first to be released on the commercial market outside the United States was the Abbott Vascular Bioresorbable Vascular Scaffold (BVS), also known as the Absorb stent. BVS data shows an outstanding low rate of late-stent thrombosis (LST). All of the stent thrombosis seen with the BVS occurs in the short term prior to the stent dissolving, but when compared to the control of the metallic Xience stent, LST continued to rise long after the BVS had dissolved, Abizaid said.
“I believe ongoing randomized trials will establish bioresorbable scaffolds as the default workhorse therapy,” Abizaid said. “I don’t expect to see any major differences between bioresorbable and metal stents.”
“Dissolvable stents may be a future game-changer for the way we treat coronary artery disease and heart attack in the United States if proven to show clinical benefit in this nationwide clinical trial,” said Samin Sharma, M.D., director of clinical and interventional cardiology at Mount Sinai Medical Center in New York. The center is testing the BVS in the ABSORB III clinical trial, which will be used to seek FDA approval for the BVS.
“The rapid completion of enrollment in the ABSORB randomized trials is a testament to the interest among doctors and patients in advancing new options to treat heart disease,” said Gregg Stone, M.D., FACC, FSCAI, director, cardiovascular research and education, Center for Interventional Vascular Therapy, Columbia University Medical Center, New York-Presbyterian Hospital. “Absorb represents an entirely new approach to helping people with heart disease by doing the job of a metallic stent, but then disappearing.”
However, several interventional experts commented at ACC that bioresorbable stents will not become a workhouse until they can prove their worth in longer and more complex lesions.
Abbott has spearheaded development with its BVS. By far the BVS has the most clinical experience, with more than 13,000 patients around the world having been treated with the device. The BVS is a drug-eluting stent (DES), delivering everolimus. It gained European CE mark in 2011.
Abbott initiated the ABSORB III clinical trial in the United States in January 2013 in a bid for FDA approval. It completed enrollment in April. The randomized controlled trial includes about 2,250 patients, the majority in the United States. It compares the performance of Absorb to Abbott’s Xience family of drug-eluting stents.
The ABSORB EXTEND Trial compared Xience to Absorb. Bernard Chevalier, M.D., FACC, Institut Cardiovasculaire Paris-Sud, France, shared some of the key trial findings at ACC 2014. The biggest news was that there is no significant difference between the two stents in the trial. He also pointed to the target lesion failure (TLF) rate to show Absorb might be superior to medal stents, with a rate of 5.5 percent, compared to 8.6 percent for Xience.
Abbott is also testing the Esprit BVS in trials for use in the superficial femoral artery (SFA) or common or external iliac arteries. The ESPRIT 1 trial angiographic and ultrasound follow-up showed widely patent arteries sustained to six months with a zero percent restenosis rate. No scaffold recoil was observed.
Other Bioresorbable Stents
In May 2014, Elixir Medical received European CE mark approval for its DESolve 100 novolimus-eluting bioresorbable coronary stent. It offers a scaffold with a thinner strut profile of 100 microns, which is smaller than the BVS at about 150 microns. DESolve is designed to degrade within one year.
Other companies developing bioresorbable stent technologies including Biotronik, Kyoto Medical Planning, Micell Technologies and Reva Medical. Terumo purchased Arterial Remodeling Technologies in March, which is developing a drug-eluting bioresorbable scaffold for the coronary arteries. Boston Scientific made a major investment in January in Amaranth Medical, which is seeking European approval for the Fortitude drug-eluting bioresorbable stent. Funding will support development of the next-generation Fortitude with thinner struts.
Restoration of the Vessel
One of the interesting findings from the ABSORB clinical trials has been the return of vasomotion and dilation after the stent dissolves. One of the top experts on the Absorb stent is Patrick Serruys, M.D., Ph.D., professor of interventional cardiology at the Thoraxcentre, Erasmus University Hospital, Rotterdam, the Netherlands, who unveiled the finding in the ABSORB Trial. He said this may change the way stenting is viewed in the future, more as a temporary repair to help the body heal on its own and return to its natural state without leaving behind permanent metal implants.
“The Absorb may provide unique benefits not possible with metallic stents, including increases in the average area within the blood vessel, reduction in plaque and improved vessel movement over time,” Serruys said. “As the body of data and real-world experience increases for Absorb, we are seeing compelling evidence that a temporary scaffold that dissolves completely after doing its job represents the future of interventional cardiology.”
Stent Thickness Issues
Bioresorbable stents may offer some improvements over metal stents, but they need to perform as well as metal stents to show any real benefit, said Elvin Kedhi, M.D., Ph.D., interventional cardiologist, Isala Klinieken, Zwolle, The Netherlands, during ACC 2014. He said a major drawback is the bulky thickness, since they require more polymer to match the structural strength of metal stents. This limits maneuverability in smaller or tortuous vessels.
Metal stents have a thickness of about 80 microns, while the BVS is about 150 microns. This makes for a large crossing profile of about 1.4–1.5 mm, so the BVS can sometimes be challenging to deliver. However, Kedhi believes the data from ongoing trials today using the most current generation of bioresorbable stents will open the door for mainstream use in the coming years.
While the stent offers potential benefits over metal stents, Serruys said there are some drawbacks. Stent recoil has been an issue after balloon expansion of the BVS. He said the BVS’s recoil rate is 6.7 percent, compared to metal stents at 3.4 percent. This is better than the original version of the Absorb first used in trials. Changes in the BVS polylactic acid chemistry helped reduce recoil in the current generation stent.
Treating More Complex Lesions
“I believe the BVS and a new generation of BVS will slowly replace metallic stents in many coronary lesions,” said Antonio Colombo, M.D., FACC, chief of invasive cardiology, San Raffaele Hospital, Milan, Italy. He believes bioresorbable stents offer a new treatment option for long-defuse coronary disease, which today is either left alone and treated medically, or requires a “full-metal jacket,” where the entire vessel is filled with stents. He said bioresorbable stents offer the ability to perform a “full plastic jacket” that will not permanently stay in the vessel.
Another area where bioresorbable stents may solve an ongoing problem with permanent implants is bifurcation stenting. Colombo has performed about 100 bifurcation stent interventions with the Absorb using different approaches.