Taking on ‘impossible’ strokes

If you had an ischemic stroke in the early 1990s, the outlook was bleak. There were no treatments. You were about twice as likely to die from a stroke back then as you are today. And if you lived, chances are you would depend on caregivers for the rest of your life. Most medical researchers avoided this field, because treating and reversing stroke was considered impossible.

But Dr. Michael Hill isn’t afraid of tough problems — in fact, he’s drawn to them.

He chose to specialize in stroke neurology during his residency training in internal medicine in early 1995. “At the time, stroke was a frontier area,” says Dr. Hill, now a professor of neurology at the University of Calgary. “It was motivating to see what we could do to treat people.”

His early work collecting data on patients across Canada helped support the 1999 conditional and then 2003 final Health Canada approval of clot-busting drugs (thrombolytics) for treating ischemic stroke, which dramatically improved patient outcomes. Today, these medications are an essential part of the stroke treatment toolkit.

His most monumental challenge to date — co-leading a clinical trial of endovascular treatment (EVT) for ischemic stroke, called ESCAPE — revolutionized the field.

This year, Dr. Michael Hill will be inducted into the Canadian Medical Hall of Fame for his groundbreaking work in stroke research. But for him, that’s not the greatest reward. What makes the hard work all worthwhile is knowing that in 2025, a stroke doesn’t have to mean the end of a full life. Thanks to the advances he and his colleagues have made, people living with stroke can return to the job they love, ride a dirt bike again or walk their daughter down the aisle. 

He gave Heart & Stroke the behind-the-scenes story of this breakthrough in stroke treatment.

Let’s start with endovascular treatment (EVT) for ischemic stroke. Can you explain what that is?

When you perform EVT, you advance a catheter inside the arterial system to the brain. For a stroke, we typically go in through the femoral artery in the groin, then thread the catheter up through the aorta and the carotid artery into the head, to reach the blood clot lodged in the brain. Then we try to remove it in one of two ways.

One way is to use a retrievable stent, a small cylindrical wire mesh tube with openings that can snare the clot. Another is to use an aspiration catheter, something like when you use your vacuum cleaner with a wand.

It’s messy — like taking an old cork out of a 90-year-old bottle of port. Sometimes we are able to retrieve all or nearly all of the thrombus.  Other times, the clot may crumble and fracture like an old cork, but the brain deals with it remarkably, and when we pull the catheters out, you’ve got normal or near-normal blood flow.

What gave you the idea for the ESCAPE trial?

I worked closely with two colleagues in Calgary, Dr. Mayank Goyal, a neuroradiologist, and Dr. Andrew Demchuk, a stroke neurologist.

The idea for the ESCAPE trial evolved from other work that we were doing. In Calgary, we had taken a great interest in the imaging of the brain with CT and MR imaging — understanding what the brain looks like and how it reacts after stroke.

We were already looking into EVT using intra-arterial delivery of clot-busting medications in one study, but with less attention to the impact of how quickly treatment was administered and how patients were selected for treatment using brain imaging. So, we addressed both imaging and speed in the ESCAPE trial, as well as testing new technology to refine the technique.

What was the new technology?

It was the use of open-cell stents, the so-called stent retrievers, for stroke.

This development was partly serendipitous. These open-cell stents were used to repair aneurysms. A couple of people, including my colleague Dr. Goyal, noted during an aneurysm procedure that when a clot formed near the aneurysm, when they pulled the stent back the clot was snared in the stent.

The same happened with another group. So, then it was tested: They used an open-cell stent, meant for aneurysms, in a stroke case, and it snared the clot and pulled it out, and the patient got better.  We immediately realized, “This is effective and real!”

How did you launch ESCAPE?

We started in Calgary and recruited 11 of our colleagues at sites in Canada and 11 other sites around the world to participate. There was one in Ireland, three or four in the United States; we had four sites in Korea and a couple in Germany. We gradually cobbled this together and eventually had 22 sites. The first patient was enrolled in 2012.

How did you raise the money to fund this trial?

That story is a long one punctuated by heartburn and sleepless nights. At several points during the trial, we did not think we’d have enough money to keep going. We went to the Canadian Institutes of Health Research (CIHR) four times and were rejected four times.

Fortunately, at the time, I held the Heart & Stroke Foundation/Hotchkiss Brain Institute Professorship in Stroke Research, and Andrew Demchuk held the Heart & Stroke Foundation Chair in Stroke Research at the University of Calgary.

We also got an initial grant from the stent manufacturer and later a supplemental grant and some philanthropic funds from the University of Calgary Hotchkiss Brain Institute, plus we had some philanthropic money from the Department of Clinical Neurosciences and finally a small grant from the CPSIN network. Thus, we had consortium funding, and it was all knitted together.

You said speed of treatment was crucial. How did you ensure teams were working fast enough?

Dr. Goyal and I went to each site twice during the trial to cajole, prod and encourage speed and careful patient selection. We, essentially, took the bullwhip out to demand speed. I’m using this term facetiously, of course, but it was about teaching everybody and saying, “Come on, guys, you have to move faster.”

When did you learn that your intervention was making a difference? 

We were blinded to the outcomes of our trial – we did not know which person got which treatment. This is a mandatory part of trials and avoids the possibility of biased decision-making during the execution of the study.

In the fall of 2014, we were scheduled to have an interim analysis, to formally assess safety and efficacy. At the interim analysis, an independent group called the Data Safety Monitoring Committee (DSMC) looks at your data. Their job is to protect the safety of the patient. They may recommend you carry on with your trial or stop your trial. If the intervention is clearly unsafe or clearly effective at this stage, recommending stopping the trial can occur.

All the criteria of success were met— including lowering death rates and ensuring that saving more lives didn’t mean leaving more people disabled — and so the DSMC told us we should stop the trial and analyse the full results.

How did you feel?

Let’s just say that was a pretty fun call!

Naturally, we believed that we had a treatment that simply needed proving because this was the impetus for starting the trial in the first place. We already had a sense that we were on the right track. If someone comes into emergency, they’re paralyzed, and you do a procedure, and then they pick up their hand, give you a high-five and say, “Thanks, Doc,” on the table, you know something’s going well. Those high-fives actually happened and continue to happen around the country. It was quite impressive.

But what we did not expect was for the outcomes for EVT to be as dramatic as they were.

What were the final results?

EVT reduced the number of deaths by half. And for every four people you treat, one additional patient recovers well enough to carry out everyday activities independently.

It was just dramatic.

These are the worst types of ischemic stroke — the big, bad ones, where you are completely paralyzed, and you can’t speak, and you’re nearly unconscious. Untreated, mortality is very high. But after EVT, in some cases people were walking out of the hospital two days later. That’s fantastic, right?

What was the reaction in the medical community?

Pretty positive that this was possible.

How quickly could EVT be widely introduced into stroke protocols around the world?

Neurointervention as a field had been established for treating other conditions, such as aneurysm, so there was already a small group of doctors who could perform the EVT procedure.

And since we were not testing a specific drug or therapy that needed regulatory approval, that made it possible to roll this treatment out within weeks. The most gratifying part was that the 11 hospitals in Canada that participated in our trial were able to just turn around and treat people immediately.

Ten years later, how widely available is it in Canada?

About 90% of the population lives within one hour of a CT scanner. And between 25 and 30 hospitals perform EVT across the country.

If you live far away from a major centre, you’re not going to be able to get EVT. But one of the legacies of this study has been that more people are interested in getting involved and treating stroke. We’ve been able to train lots of people, and they’re now disseminating across the country and training others.

Globally, EVT is now widely used in major health systems everywhere. A total of five major studies were published in 2015, including the ESCAPE trial, that all essentially reached the same conclusion — that EVT was a highly effective treatment for major ischemic stroke. This consistency of treatment effect in five different populations cemented the results, and the treatment was rapidly moved into real-world delivery.

What role has Heart & Stroke played in supporting your research over the years?

The first grant I ever got was from a joint Heart & Stroke-CIHR investigator fund in 1999. Then I’ve had other grants from Heart & Stroke over time. And of course, the professorship for myself and the chair funds for Dr. Andrew Demchuk, that were both crucial to keeping the ESCAPE trial going.

What does it mean to you to know that EVT has helped someone recover from a potentially fatal stroke?

It’s terrific to hear those stories. There are so many now and they all move me. It’s fantastic to hear people are recovering so well and being able to get back to their lives.

That’s what we do it for.