Cath Lab Digest talks with L.N. Hopkins, MD, FACS, Department of Neurosurgery and Toshiba Stroke and Vascular Research Center, Department of Radiology, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York.

What has been the standard treatment for ischemic stroke and why we are at the “dawn of a new era”?

For a number of years, the only approved treatment for stroke has been intravenous (IV) tPA, which is a lytic drug, meaning it dissolves clots. While tPA has been good for tiny clots in the circulation of the brain, it also has been the only approved treatment for stroke for many, many years. A heart attack and a stroke are very similar in that a major artery is blocked. If we think about the treatment of acute stroke, it is identical to the treatment of heart attack. If we go back 20 years in the treatment of heart attack, people were using lytics for treatment. For many years, that was the standard of care. Then, over a number of years, studies showed that physically opening up the artery by putting in a stent was a much better — in fact, lifesaving — treatment for acute heart attacks. For many years, stroke has been similar to a heart attack in that when it happens, it is devastating and also similarly, lytic drugs were the only approved treatment for many years. Development of any additional treatments has lagged behind that for heart attacks, because the technology required is more challenging for stroke. The arteries in the brain are much harder to access and are much more fragile than coronary arteries. Risks of stroke intervention were initially high, but the technology has evolved over the last 5-10 years, and better and better techniques have arisen. It has been a difficult and slow evolution. For heart attacks, so many are occurring, it is easy to accumulate a large number of patients and study them. For strokes, getting patients to the angio suite and removing a clot has been a much more challenging scenario, because one, there hasn’t been the level of public awareness as with heart attack, and two, when someone has a stroke, they are not clutching their chest complaining of chest pain. They may be lying quietly or simply not moving. Public awareness that something could be done for acute stroke has been, I think, lagging. 

A year ago, there were three trials reported in the New England Journal of Medicine: SYNTHESIS¹, IMS III², and MR RESCUE³. These were trials done over the course of many years, comparing intervention to IV tPA, but the trials went so far back in time that the intervention used in most patients involved only squirting a little IV tPA directly into an artery or using a wire. Trial researchers initially did not have any of the newer technology such as the Solitaire FR (flow restoration) Revascularization Device (Covidien), which can capture and remove the clot. In fact, all three trials came out negative for intervention, but the data demonstrated some important things. One was that intervention in the brain is now quite safe. The safety in those trials was good. Second, only about 5% of patients in all three trials actually got what we would call modern clot retriever therapy, so you couldn’t expect the remaining patients to do that well, and they didn’t. However, the reason I say there has been the “dawn of a new era” is that several very important studies have just been terminated. The first was called the MR CLEAN trial in Denmark (Multi center Randomized Clinical trial of Endovascular treatment for Acute ischemic stroke in the Netherlands).⁴ That trial showed a significant benefit for intervention as opposed to IV tPA. It only makes sense. If you have a large artery blocked, IV tPA is kind of like peeing in the ocean — it is not going to do much. Yet removing the clot and restoring flow in a large artery can make a huge difference, and this was demonstrated in the MR CLEAN trial. More recently, a Canadian trial, ESCAPE (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times), compared IV tPA out to 4 hours to intervention out to 12 hours in a randomized, prospective fashion like MR CLEAN.⁵ The data safety and monitoring committee decided to halt the ESCAPE trial early, because it demonstrated overwhelming benefit for intervention. Now we have very encouraging randomized, prospective data showing that intervention is better than IV tPA for patients with large arteries that are occluded in acute stroke. We now have a wonderful opportunity to really go after acute stroke. We need industry to keep working to make better and better products. We need more people to be trained in stroke intervention, because strokes happen anywhere and anytime. In order to have a real impact, we will need an army of practitioners able to reverse a stroke when it occurs. Speed is of the essence. The faster we get the clot out, the better the results. We are at the dawn of a new era.

How does the Solitaire device work?

It resembles a stent that is attached to a wire. When you deploy the device, it does two things: first, when the “stent” is deployed and opens up, it immediately restores flow in the artery, giving the brain a rest from the ischemia it has been suffering. The device is allowed to sit for a few minutes in order to let the clot become incorporated into the stent. Then the device is slowly pulled out through a larger catheter, and the clot comes with it. In about 80-90% of the cases, we are able to get the artery open. Sometimes completely, and sometimes almost completely, but in 80-90% of the patients, we can get the artery open using this technique. If everything else lines up, it can result in a spectacular cure. I can’t remember seeing anything else in medicine more exciting and impressive than what happens when a patient who is paralyzed on one side and unable to speak with a clot in his middle cerebral artery, within seconds of removing the clot, starts to move, and within minutes, starts to talk, wondering where he is and what happened. Within a few hours, the patient can be completely back to normal. It doesn’t work for every patient, because it depends on how much damage has been done by the stroke. But in many patients, it is possible to achieve a significant or total reversal of what would be a devastating, life-ending event.

Any final thoughts?

I think we need to carefully assess the data from these trials. If the Solitaire is as solid as it looks initially, we need a full-court press to position stroke intervention as the frontline treatment for acute stroke in patients with large arteries that are occluded. 

References

1. Ciccone A, Valvassori L, Nichelatti M, Sgoifo A, Ponzio M, Sterzi R, Boccardi E; SYNTHESIS Expansion Investigators. Endovascular treatment for acute ischemic stroke. N Engl J Med. 2013 Mar 7; 368(10): 904-913.
2. Broderick JP, Palesch YY, Demchuk AM, Yeatts SD, Khatri P, Hill MD, et al; Interventional Management of Stroke (IMS) III Investigators. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med. 2013 Mar 7; 368(10): 893-903.
3. Kidwell CS, Jahan R, Gornbein J, Alger JR, Nenov V, Ajani Z, et al; MR RESCUE Investigators. A trial of imaging selection and endovascular treatment for ischemic stroke. N Engl J Med. 2013 Mar 7; 368(10): 914-923.
4. Berkhemer OA, Fransen PS, Beumer D, van den Berg LA, Lingsma HF, Yoo AJ, Schonewille WJ, Vos JA, Nederkoorn PJ, Wermer MJ, van Walderveen MA, Staals J, et al; MR CLEAN Investigators. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015 Jan; 372(1): 11-20.
5. Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE). Available online at https://clinicaltrials.gov/ct2/show/NCT01778335. Accessed January 20, 2015.