In 2006 Professor Patrick W. Serruys introduced the use of fully biodegradable drug-eluting scaffolds. This new stent was to eliminate the presence of a metal stent which was a permanent metallic foreign body in the coronary circulation. This revolutionized the then field of interventional cardiology.
I had the great pleasure of interviewing Patrick Serruys for ACCEL in 2007. I asked him, “How did this idea of biodegradable stents come about?” [1].
He responded that: Maybe we should go back a little bit to the early days of the metallic stent in 1986 when we started to push this piece of metal into the coronary artery. At that time, I had a strange feeling of guiltiness. It was against nature, but it worked. It’s a good scaffolding device, but it is clear that the metal stents are only necessary for six months. When the healing process has taken place, this piece of metal should disappear. So, it has been a long, long dream to have a scaffolding device disappearing after having performed this function. It’s as simple as that.
All things considered, it would be preferable not to have a metallic cage in the coronary artery. One must realize that when the metallic cage is there, you can no longer have extensive lumen and vessel remodeling. If vasomotion is important in the cold weather or during exercise, there is no vasomotion at that site. So, there is plenty of reason why it should be something transient, and that is the biodegradable stent standard.
What is interesting is that the stent is made of a polymer of polylactic acid. This is something that has been in medicine for the last forty years, so it is metabolized by the Krebs citric acid cycle. As long as the stent is metabolized very slowly, one can fool Mother Nature, and one will not have a cellular reaction against a foreign body. That is the beauty. It took almost 20 years to get there.
There are data that indicate that the bioabsorbable stent is bioabsorbed at six months. All the data that was available, of course, was obtained in healthy animals, so nothing was known about what was going to happen in a patient. So, in the ABSORB trial, 30 patients were evaluated with angiography and intravascular ultrasound (IVUS).
At six months, all the patients in the ABSORB trial were doing well, without any evidence of acute occlusion. When Professor Serruys started his career 20% of the patients evaluated had subacute occlusion, so obviously some progress has been made with subacute occlusion. No one in the ABSORB trial had a reintervention of the stented segment using the biodegradable stent, but of course they were very small numbers.
What has been observed with angiography is that usually with bare metal stents, one ends up with the late loss of 0.8 mm. With a very good drug-eluting stent, late loss is around 0.1 or 0.2 mm. The late loss with a biodegradable stent was 0.44 mm, so this was really in-between the bare metal stent and the drug-eluting stent. That was the observation that was made with angiography. IVUS gives a cross-section assessment of the vessel, the external elastic membrane, the stent, and what is growing inside the stent. The neo-intimal inside of the stent is 0.3 mm2, so it is even less than the good drug-eluting stent. Drugs go very well in the bioabsorbable stent.
The critical observation is that by watching the ring of the struts, reduction of the stent area can be assessed. There was a reduction of 11.6% of the stent area. In the metal stents, of course, it is stable. It doesn’t move. Here, in the circle of struts of a bioabsorbable stent, it became somewhat smaller – 11.6 mm, and that immediately gives one on angiography a late loss of 0.44 mm. It is not due to neo-intimal hyperplasia. It is mainly due to the shrinking.
The ABSORB study consisted of 30 patients at six institutions. Two institutions never found the appropriate patients for study. In Rotterdam we had 16 patients with very short lesions. The stent was 12 mm long, so you have to find a lesion of 8.5 mm maximum to be covered properly by the stent. This was the first experiment that provided preliminary data on the use of biodegradable stents.
There is nothing special about deploying the stent. It is not difficult. What is amazing is that the acute recoil is immediate, so you measure that by inflating the balloon and looking at the diameter of the vessel immediately after deployment. The acute recoil is 6.4% and the metal is 4.2%. Thus the biodegradable stents have been processed in order to achieve almost the same radial force and the scaffolding properties of the metal stents. This, in itself is a great achievement.
Obviously, there is more to come in this direction. Renu Virmani liked the concept of the biodegradable stent but made the point that you must do a prospective randomized trial to prove that thrombi are not lurking early or late after deployment. That is the great responsibility that investigators have when one is testing something in an uncharted field.
Professor Serruys indicated that everything at his home is now biodegradable, and his wife knows a lot about thrombosis, stenting, angioplasty, etc., so she told him that he was now entering the biodegradable phase of his life.
Finally, if we go back to 2003, when Renu Virmani said, “I think it’s time to think about biodegradable materials”, we are now there.
Professor Serruys finishes his interview by saying, “You have to listen to this lady. That’s for sure.”
What is in store for the future? Only time will tell as newer stent types are being developed to overcome the problem of stent thrombosis after stent deployment.
I am told that in the next decade, Professor Serruys will dedicate his scientific and clinical career to re-revolutionize the field of interventional cardiology by using local percutaneous treatment to alter the atherosclerotic process.
In the October 2015 issue of the JACC Intervention an article was published entitled “Very Late Scaffold Thrombosis’’ [2]. This was a study of four patients who underwent intracoronary imaging and histopathologic and spectroscopic findings after late scaffold thrombois. During the study a total of 171 patients were revascularized at three sites using the Absorb Bioresorbable Vascular Scaffold. The authors of this article indicate that late stent thrombosis can occur in these stents related to scaffold discontinuity and restenosis during the reabsorption process.
According to Dr. Greg Stone, the issue of late scaffold thrombosis can only be addressed by the performance of a large scale randomized evaluation of these bioresorbable stents versus drug eluting stents [3]. There is an ongoing trial called ASBORB IV to address this issue. Dr. Stone goes on to the say that at the present time we should not be “concerned” about very late stent thrombosis after bioresorbable vascular scaffolds but we should be “aware”.