How does the Genous R stent address some of the problems we see with bare metal stents (BMS) and drug-eluting stents (DES)?

If you look at a 2002 publication in Herz (a German cardiology journal) from Prof. Renu Virmani’s group¹ comparing the results of a DES implantation to intravascular brachytherapy, basically what this study showed is an absence of vessel healing combined with a chronic inflammatory reaction after DES placement. This was remarkably similar to what happens to the vessel wall after brachytherapy. This study showed that the effect of DES placement (it was either an everolimus- or paclitaxel-eluting stent), resulted in an absence of healing. There was no endothelialization and there was chronic inflammation, both as a reaction to the drug and as a reaction to the polymer that was coating the stent. If you look at the healing response to a BMS, there is an inflammatory reaction, but it is temporary. Endothelialization is complete after a few months and the inflammatory cells disappear after some time.

If you look at the animal data from the Genous stent studies, you can see that endothelialization after Genous stent implantation is enhanced, so the process is much quicker. Even after 48 hours in the pig coronary artery, the endothelialization is rapidly occurring both on the stent struts and in the areas between the struts. The inflammatory reaction is also there, but it is not as serious as the inflammatory reaction after drug-eluting stent implantation. This concept of vessel healing and enhanced endothelialization is likely to translate into a lower incidence of restenosis and a lower risk of stent thrombosis after placement of a Genous stent in patients. Clinical experience from the First-In-Man and the HEALING-II study, of which the principal investigator was Prof. Patrick Serruys, provided the first indication of clinical effectiveness and safety.

e-HEALING is a multi-center, worldwide prospective registry of patients treated with the Genous Bio-engineered R stent. What has this registry shown so far?

CE mark was obtained and the Genous stent was marketed in Europe and Asia Pacific. At that time, it was then possible to start a registry. The aim of the e-HEALING Registry is to enroll 5,000 patients treated with a Genous stent. Of course, one of the requirements is for the patients to enroll them in e-HEALING is that they were on statin treatment prior to Genous stent implantation. The primary endpoint in e-HEALING is a clinical outcome of 6 to 12 months. We showed preliminary clinical results from the e-HEALING Registry during the EuroPCR symposium in Barcelona this past May, and we now have a cohort of over 2000 patients with a 30-day outcome and a cohort of over a 1000 patients with a 6-month outcome. Both of these outcome data, 30-day and 6-month, look quite good, with MACE rates comparable to the Cypher and Taxus registries and a low stent thrombosis. We are now enrolling a little over 200 patients a month in the e-HEALING Registry, and I think at this time, 3800 patients are enrolled. We expect to finish enrollment before the end of 2007.

Is there a particular patient subset that would benefit most from the Genous stent?

That’s a very important question. One reason we required two weeks of statin therapy is because it is likely to increase the number of endothelial progenitor cells and also increase their functionality. Therefore, we expect patients who are on statin treatment will benefit from Genous stent implantation. It was agreed from the beginning, however, that if patients are added into the registry but have not been on statin therapy for 2 weeks, we will still look at these patients. So we will have a subset of patients that have been on statin therapy for a shorter period of time than the required two weeks. It will be very interesting to look at these patients and see if two weeks or maybe one week of statin therapy will be sufficient.

In addition to statin therapy starting two weeks prior to stent placement, what type of pharmacological regimen is required?

There is no requirement for any accompanying drug treatment at the time of stent implantation. After Genous stent implantation, the recommendation is for 4 weeks of dual anti-platelet therapy. Clearly, patients that cannot be treated with long-term dual anti-platelet therapy, e.g. because they are scheduled for surgery shortly after the percutaneous coronary intervention (PCI) procedure or because of an increased risk of bleeding, may benefit from Genous stent placement. The time the patients are on dual-antiplatelet therapy is also captured in the e-HEALING Registry. Of course, we will also look at patient subsets that have high risk of clinical restenosis, such as diabetics or patients with long lesions or small vessels.

Can you share details of a case or two where you have used the Genous stent?

As a matter of fact, I treated two patients with a Genous stent this morning. One patient was going to undergo major bowel surgery because of a carcinoma, and the surgeons wanted to treat him as soon as possible. We put in a long Genous stent in the right coronary artery. The patient is going to be on dual anti-platelet therapy for two weeks and then we stop the clopidogrel. The surgeon is willing to operate with aspirin treatment, but he doesn’t want to do the operation with the patient on dual anti-platelets. This means the patient is ready for his bowel surgery in two weeks plus five days.

The other patient was a patient that had large aneurysms in the dominant right coronary artery. The presence of these aneurysms signifies an increased risk of stent thrombosis, which was one of the reasons that I treated this patient with a Genous stent. I expect it to be less thrombogenic than a drug-eluting stent. A large aneurysm which is due to possible remodeling is an anatomical situation which is not infrequent. Sometimes in the past we would do spot stenting and leave the aneurysms alone, but now with the Genous stent we can just treat the whole segment.

If I look at the practice in our cath lab, of course, we have become more and more aware of the fact that you don’t want to have patients on dual anti-platelets for 6 months or 12 months or even longer. Thus there are many patients that we now treat with the Genous stent because we want to put them on dual anti-platelets for a shorter period of time, as we did with bare metal stents.

Can you tell us about the stent from an operator perspective?

The Genous stent became commercially available to our center in September 2005, and prior to that we participated in the HEALING II study, so our center had some experience with Genous prior to it becoming commercially available. Of course, the stent platform is the bare-metal R stent, which we were using in our cath lab before the bio-engineered version. We are particularly fond of the design, which is perfectly suited for treating bifurcated lesions. I think the deliverability of the Genous is better than the Cypher, and comparable but a little better than a Taxus stent. We have Cypher and Taxus and we now have the Xience V stent available in our cath lab, and I think that the Genous is comparable to Xience V in terms of the profile and trackability.

Considering your experience with the Genous stent, how do you feel another type of stent under development, the bioabsorbable stent, will fit into patient treatment options?

It’s an interesting concept. If you think of having a metal scaffolding in the proximal part of your coronary artery, when the vessel is healed and the vessel is patent, then stented segments usually stay stable. It may very well be that having a metal scaffolding in the proximal part of your coronary artery is not a bad thing. You may think that it is unnatural to have metal in your coronary artery, so if you have a bioabsorbable stent which performs as well as a metal stent, it could be an advantage.

I think bioabsorbable stents may prove useful in cath labs where they have the tendency to stent long segments of the coronary arteries. If you give a patient a full metal jacket in the right coronary artery, and he subsequently is eligible for coronary artery bypass surgery, then all the stented segments provide the surgeon with a problem where to put his bypass graft? That may be an application for bioabsorbable stents.

From the data I have seen at this particular time, I think bioabsorbable stents do not have the scaffolding properties of metal stents. There is the issue of control over the timing of absorption of the stent, not too fast but not too slow. There will be recoil and particularly in the calcified vessels, I would not put in a (current generation) bioabsorbable stent. However, I expect over time, new technology will provide us with bioabsorbable stents with better mechanical properties.

What are the future plans for Genous stent data presentation?

We have done a pilot study here at Academic Medical Center (AMC), randomizing patients between a Genous stent and Taxus, and we are doing follow-up angiograms on these patients. I am not sure that the full dataset will be available at the time of TCT this October, but hopefully it will be. We will also show results from e-HEALING at TCT.

About three years ago, I predicted that there was going to be a serious concern about late stent thrombosis, based on seeing just our own cases of late stent thrombosis at AMC. With the adoption of DES by the interventional community, what is happening now could be foreseen a couple of years ago.
At our center, we have been cautious with the use of DES. In the beginning, the use of DES in our lab was just in patients that otherwise would have gone on to bypass surgery and treatment of in-stent restenosis. We are still using a maximum 20-25% of DES in our patient population. In particular, the patients who are treated for acute myocardial infarction and undergo primary PCI are treated with BMS. Now, increasingly, we are treating some of these patients with DES, but we are also turning to the Genous stent for longer segments and chronic total occlusions. I think that at the present time, Genous is one of the candidates that will likely replace the first generation of DES, because the performance is good and there is no risk of late stent thrombosis.

Dr. de Winter can be contacted at:

Academic Medical Center
Amsterdam
Dept of Cardiology, B2-137
Meibergdreef 9
1105 AZ Amsterdam, The
Netherlands
Email: r.j.dewinter@amc.uva.nl