Colin Derdeyn

Colin Derdeyn

A conversation with Colin Derdeyn, MD, Chair and Departmental Executive Officer of the Department of Radiology, University of Iowa Carver College of Medicine, about the late complications of stenting for intracranial atherosclerotic disease and the challenges posed by new stroke treatments.

Interviewed by José G. Merino, MD, Associate Professor of Neurology, University of Maryland School of Medicine.

They will be discussing the paper, “Nonprocedural Symptomatic Infarction and In-Stent Restenosis After Intracranial Angioplasty and Stenting in the SAMMPRIS Trial (Stenting and Aggressive Medical Management for the Prevention of Recurrent Stroke in Intracranial Stenosis),” published in the June 2017 issue of Stroke.

Dr. Merino: Good afternoon. Can you tell us what prompted this secondary analysis of the SAMMPRIS data?
Dr. Derdeyn: From SAMMPRIS, we learned that there’s potentially great value for dual antiplatelets and statins, along with aggressive risk factor management for patients with intracranial atherosclerotic disease (ICAD).  We also learned that in this setting, there is a much higher complication rate from stenting than we thought, mainly due to a lot of perforator strokes, particularly in the basilar territory, and that the procedure is associated with a risk of intracranial hemorrhage, perhaps due to reperfusion. These short-term complications limit the value of stenting for ICAD.

The question that we sought to answer in the latest analysis was: If we improve the procedure and avoid the perforator segments, what other areas do we need to be thinking about, and focusing on, for intracranial angioplasty and stenting to be able to be proven effective? What are other problems from the procedure?

We wanted to look at the late complications in the stenting arm of SAMMPRIS. We know a lot about the short-term risks, the 30-day perioperative events, but what about the after-30-day events? That’s really what this analysis was about. We looked at the late primary end point, which was ipsilateral stroke in the territory, but also considered TIA and completed infarction with temporary signs (CITS). We wanted to know, what other hurdles or problems need to be overcome, or do we need to be aware of, as we test new intravascular interventions for ICAD?

Dr. Merino: You found a relatively high late in-stent restenosis (ISR) rate. Is there something about the patients in the trial or the study design that may explain the high rate?
Dr. Derdeyn: I don’t think that the rate was much higher than prior case series. Certainly, it is higher than some case series that have been published from Asia, but the rate of ISR was not too different from many other registries.

What was new, and an important wrinkle for our study, was that the SAMMPRIS protocol did include any surveillance studies at six months or a year after implantation to look for asymptomatic ISR. This means that we do not really know what was the rate of asymptomatic ISR, and we do not know what would be the impact of early and aggressive treatment in this setting. Could it have reduced symptomatic ISR? The reason why we did not screen for it is that there is not great evidence about how to best treat ISR. Should you re-angioplasty it? There are risks with doing that.

But if somebody had a TIA or a stroke, there were no restriction in pursuing DSA, CT, or MRI to look for ISR and to treat it. The diagnostic evaluation and treatment was determined by each clinician. As a result, we got a very, very robust and unbiased estimate of the rate of symptomatic ISR because these patients did get imaging. We also know that the complication rates for treating ISR were not negligible, and we did have a fair number of complications in patients with symptomatic ISR who were treated.

One of the findings of our study is that 18 of the 200 patients who had a stent (almost 10%) had a stroke after 30 days. Most of these were attributable to ISR. Future trials that look at angioplasty and stenting need to include adequate follow-up to capture this complication; it will be important to take these late ISR into account for future trials of stents against medical therapy.

Dr. Merino: Patients with ICAD who had angioplasty and stenting were treated with two antiplatelet agents. What else should clinicians do for these patients to prevent ISR? Or do we need future trials to answer this question?
Dr. Derdeyn: This is a good question, and I do not really know the best way to answer it other than to say that the current indications for ICAD stenting are pretty limited. It is reasonable to consider stenting for somebody that has a known, fixed lesion and who has failed maximal medical therapy, although there is no data that supports angioplasty stenting for patients who have a stroke despite being treated with Aspirin, Plavix, and a SAMMPRIS-like regimen. That is not to say that you should not consider it. Some patients with ICAD are being treated with angioplasty and stenting today, including those with hemodynamically unstable situations and people that would not have been eligible for SAMMPRIS. The main thing that clinicians should recognize is that there is about a 10% risk of recurrent stroke over two years because of in-stent restenosis.

In addition, we think that there probably is a pretty high degree of asymptomatic in-stent restenosis, but it is unclear if we should look for it. We do not know the best way to treat it. What is the outcome with medical treatment alone? What are the risks of trying to re-angioplasty and stent a narrowed lesion? We know it is not zero because in SAMMPRIS, we saw several strokes attributed to treatment of ISR.

Dr. Merino: What do you think about the future options for ICAD?
Dr. Derdeyn: I think that, in general, there are two big areas that need further study. One, we need studies to identify either high-risk groups that might benefit from angioplasty and stenting or groups that will optimally benefit from medical care or something else. Natural history studies can identify hemodynamic factors. Plaque imaging studies can determine risk factors for intraplaque hemorrhage and evaluate the impact of pharmacologic intervention on plaque stability.

Then, the other big avenue is to study safety and feasibility of angioplasty and stenting in single arm pilot studies that assess if different techniques or different devices can achieve lower complication rates in a SAMMPRIS-like population. These studies have to include long-term follow-up (at least a year or two) to look for ISR to make certain that’s part of the estimate.

Dr. Merino: Thank you, this puts the findings in perspective. Now, I want to ask you about something that is related not only to SAMMPRIS, but also to the approach to stroke treatment and prevention. Your work is an example of the value of the close relationship between interventional radiologists, vascular neurologists, and others to implement valuable therapies for our patients. Can you comment on the ways to get multiple specialists working together? What are the major lessons from these studies? What are the practical implications for people at different types of institutions?
Dr. Derdeyn: Well, it is difficult to predict the future, but one thing that I think is really remarkable and positive, and probably will be a trend that will continue, is that the recent proof of efficacy for acute thrombectomy has really led to radical changes in how we practice.

Back in the old days, which I’m old enough to remember, and you are too, at a major academic tertiary care comprehensive stroke center, you really only needed one or two interventional neurologists or interventional neuroradiologists to manage the daily work load: There are not that many brain aneurysms or other conditions. For us in interventional radiology, acute ischemic stroke really was not a high volume challenge. The imperative to have a team available and to get in there quickly and to be effective was not there, but it is now. As a consequence, now hospitals need four or five people to take call and provide access to those services. And these people, at most institutions, will not all be in the same department.

In many places, including where I am now at Iowa, you have multidisciplinary teams. In addition to interventional radiologists, you need an endovascular neurosurgeon because it is key to have somebody that can also do craniotomies, clipping, and bypass if indicated. You also have interventional neurologists that can be stroke attendings and neurointensivists. And neuroradiologists also play a critical role in helping to make certain that imaging is done well.

Training guidelines are also evolving. The cath certification that is being rolled out by the Society of Neurological Surgeons, with very good support from SVIN, SNIS, and a really combined, multidisciplinary oversight group, is really pushing for standardized training guidelines that treat people that have completed these approved fellowships pretty much equivalently regardless of primary specialty.

I see the field coming together but from a multidisciplinary kind of a background and for the benefit of everybody. I was President of the SNIS when we went to the initiative to change the name at the launch of the journal. A big multidisciplinary big tent is always better.

I think that cooperation and integration is critical to support these large multi-center trials. We are seeing more and more of them, which is wonderful. We had more than five different thrombectomy trials, and we are doing several wake-up stroke intervention trials. I am optimistic that we’ll see more, and I’m optimistic for StrokeNet to help support it. too. I think this is a really good, remarkable time in neurointervention.

Dr. Merino: These are indeed exciting times for the field of stroke. Thank you very much.