Kenneth Butcher and his team
June is stroke month. Strokes can have a life changing impact on patients and their families. In 2012, more than 46,000 Canadians were hospitalized for stroke, and more than 13,000 died as a result. Thankfully, researchers are constantly working to find new ways to prevent, identify and treat strokes in order to improve patient care.
One of these researchers is Dr. Kenneth Butcher, a neurologist and a stroke sub-specialist. Butcher has a clinical research position devoted entirely to stroke, as is his clinical practice. He and his team have undertaken many different research initiatives aimed at improving outcomes for stroke sufferers.
Early anticoagulation after a stroke
Butcher's team recently investigated the safety and feasibility of starting oral anticoagulant drugs in the early phases of stroke. Anticoagulants are used to stop ischemic strokes which are caused by blood clots forming in the heart and traveling to the brain, blocking an artery.
Before 2010, there was only one anticoagulant drug available. Since that time, three novel anticoagulant drugs have been introduced. The studies for these new drugs excluded patients that have recently had a stroke and transient ischemic attack, so there was no data on the safety of using these drugs within two weeks of an event. Unfortunately, that's the population at the highest risk for another stroke. Anticoagulants are avoided in these situations because there's an elevated risk of bleeding.
To determine when to deliver anticoagulants, most physicians have an algorithm that is based on the size of the stroke, because it is known that bleeding is more common in patients with larger strokes. Butcher wanted to address this non-evidence based approach. His lab undertook a study where patients who had strokes were treated with one of the novel anticoagulants called Rivaroxaban. The team did specialized MRI sequences before and after they started the anticoagulant looking for predictors of bleeding such as micro bleeding that might not have been obvious on traditional CAT scan images.
"What we found was that a surprising number of patients have evidence of microscopic bleeding even before we started the anticoagulant," says Butcher. "Starting the anticoagulant in the patients did not worsen the bleeding."
Butcher said that in their sample they found the drug to be safe. He notes that it's a small sample and a pilot study, so it's not definitive, but it's the first safety data of its kind. Butcher's team will be undertaking similar studies with the other novel anticoagulants and arranging a larger, more definitive study in different centres across Canada.
Butcher hopes this study, and future studies will allow physicians to definitively identify patients that would benefit from early anticoagulants. Older anticoagulants were avoided because any benefits you saw were washed out by an increased risk of bleeding.
"What that means for patients is we can reduce the probability of early recurrent stroke without increasing their risk of bleeding due to premature anticoagulation," says Butcher.
Safely lowering blood pressure in stroke patients
Blood pressure is elevated in all acute stroke patients, but what to do with that blood pressure, and the cause of that blood pressure in the acute phase is highly contested. That applies to both ischemic and hemorrhagic strokes (a stroke that results in a ruptured artery or arterial within the brain causing an intracerebral hemorrhage).
Typically doctors haven't treated blood pressure in either type of stroke because lowering blood pressure lowers blood flow to the brain, which will worsen ischemic strokes. Additionally, some believe that it may induce ischemia in patients with intracerebral hemorrhage.
Although it is avoided, lowering blood pressure may be beneficial in hemorrhagic strokes. Butcher explains this concept using a simple metaphor. In a hemorrhagic stroke, you have an open artery that is leaking blood into the brain causing a hematoma (blood clot). Just like you would turn down the faucet if you had a hole in your garden hose to stop it from leaking on your lawn, you lower the blood pressure and lower the rate of bleeding.
There have been a couple of trials with mixed results about the efficacy of lowering blood pressure early on. "We haven't seen a dramatic reduction of hematoma expansion or mortality when lowering the blood pressure aggressively," says Butcher.
There are a couple of different theories to explain why it hasn't been effective. One is that is it causing harm in those patients. Much of Butcher's work in the lab has been devoted to seeing if that is the case. His team measures blood flow before and after they lower blood pressure and they do MRI scans looking for evidence of ischemia. They have published one trial showing there's no change in flow and they're doing another trial looking at MRI evidence of ischemia, which is more common than they realized, though Butcher is not sure whether or not it's related to blood pressure reduction.
The other theory is that lowering blood pressure had been largely ineffective because, as Butcher states, "the horse has already left the barn." Typically doctors start lowering blood pressure in the emergency department, but Butcher thinks this needs to happen sooner. The earliest opportunity for most stroke patients would be in the ambulance on the way to the hospital. This is difficult because in the ambulance it's not yet know what type of stroke the patient has. Typically, studies start with blood pressure at the triage department at the hospital. These studies show that patients come in with the highest blood pressure and within hours, even without treatment, it starts to fall. Butcher wanted to know if blood pressure was even higher closer to the event and was falling by the time they got to the hospital.
To examine this, a large study was undertaken. It looked at all patients with suspected stroke who had been picked up by ambulance and transported to the University Hospital. The team worked with the EMS services database to identify 1,000 patients over two years who had been brought to the hospital for an apparent stroke and linked that information to the hospital databases to look at their blood pressure upon arrival. They also looked at the imaging and identified exactly what type of stroke each patient had.
Butcher's team found that blood pressures in the hospital were similar in the ambulance, but they also found that you could differentiate the type of stroke by the blood pressure. Patients with hemorrhagic stroke had much higher blood pressures that remained stable from EMS pickup to drop off in the hospital.
"In order to really aggressively treat patients in the pre-hospital phase, we would have to move diagnostic tools into the pre-hospital setting, which means an ambulance with a CT in it," says Butcher. "But, we could start modest blood pressure reduction safely in the ambulance, because the majority of the time EMS will be treating hemorrhagic stroke patients and even ischemic stroke patients with blood pressures at that high level would have their blood pressure lowered modestly in the hospital."
Butcher thinks there's a role for EMS patients to start treating stroke earlier much in the way that they treat acute coronary syndrome now by administering clot-busting therapy in the field.
Partnering for better stroke patient care
Support from funding partners make life-changing stroke research possible. Funding for these studies comes from multiple sources. Butcher has a Heart and Stroke Foundation of Alberta, NWT & Nunavut Professorship and a holds a Canadian Research Chair in Cerebrovascular Disease. These allow him to take on pilot projects like the Rivaroxaban study without project specific funding from funding agencies. Butcher also received funding from Bayer, the manufacturer of Rivaroxaban, through an Investigator Initiated Research Proposal. Additionally, Butcher's Fellows who assisted in the studies were funded by Alberta Innovates Health Solutions.