Hope for Stroke: Expanding the Treatment Window for Acute Ischemic Stroke

Stroke is the second-leading cause of death worldwide and a leading cause of disability. Each year in the United States, more than 795,000 people will suffer a stroke, and about 133,000 people will die from a stroke. A stroke will occur once every 40 seconds, and associated costs are more than 34 billion dollars per year, including cost of health services, treatment medications and lost days of work.

The widespread impact of strokes make the new and updated clinical practice guidelines released this week at the International Stroke Conference in Los Angeles, CA very exciting. The American Heart Association (AHA) guidelines detail prehospital care, urgent and emergency evaluation and treatment and in-hospital treatment for the first two weeks. The 2018 release of these guidelines holds promise for those who suffer an acute ischemic stroke by offering treatment consideration to an expanded group of patients. These guidelines change the landscape for stroke treatment as more patients may now be eligible for treatment proven to decrease disability. These new recommendations will impact the death and disability rate of stroke across the United States and the world.

The first exciting change addresses treatment with IV alteplase. IV alteplase is a thrombolytic drug given to acute stroke patients to dissolve the clot in the artery of the brain. When IV alteplase first received approval in 1996, there were very rigid recommendations for use with strict rules about patient eligibility. These recommendations established the inclusion and exclusion criteria used to determine eligibility for treatment. The new American Heart Association guidelines released this week re-establish the criteria for treatment and address the gray area in treating ischemic stroke patients. Patients who previously would have been ineligible to receive IV alteplase may now be considered.

Prior to this recommendation, patients who recently underwent minor procedures or had mild stroke symptoms were not eligible for treatment. Now, there is an emphasis on the degree of potential disability and determining the risk versus benefit of treatment. AHA states IV alteplase should be given within 60 minutes of arrival to the hospital. Ideally, hospitals work faster to administer the medication as quickly as possible with a goal of treating at least half of the patients within 45 minutes. The guidelines now also recommend expert stroke consultation for hospitals without stroke experts on site. This consultation ideally occurs via a telemedicine device, but may occur over the phone for hospitals without telemedicine capabilities.

In 2015, the American Heart Association first recommended mechanical thrombectomy for patients with a large vessel occlusion (clot in certain large arteries of the brain) within 6 hours of the time a patient was last known well. Patients are deemed eligible for acute stroke treatment based on the time a patient was last known to be well, or without stroke symptoms. If deemed reliable, this time can come from the patient, otherwise it can come from the last person to see the patient before symptoms began. The 2018 update of the guidelines extends the window up to 24 hours for certain patients. Very often, time is a limiting factor in treatment options for acute ischemic stroke. The updated recommendations are based on the design of two strong randomized controlled trials, which demonstrated the mechanical thrombectomy treatment window for acute stroke can be extended out to 24 hours for select patients.

The DAWN trial, presented in 2017 at the European Stroke Organization Conference, looked at mechanical thrombectomy up to 24 hours with additional imaging to demonstrate viability of brain tissue. Results demonstrated 49% of patients treated had a good functional outcome (modified Rankin score of 0–2) compared to 13% in the control group. The DEFUSE 3 trial, presented at the International Stroke Conference this week, looked at treatment from 6 to 16 hours and included an expanded group of patients based on symptom severity. Results demonstrated 44.6% of patients had a good functional outcome compared to 16.7% in the control group in patients treated between 6 and 16 hours from the time last known well. These two strong trials provide an unprecedented change in stroke care. Patients who are so-called “wake up” strokes now have treatment options. “Wake-up” stroke patients are those who went to bed in their usual state of health and woke up with symptoms. Previously, these patients were often ineligible for treatment because of an unclear symptom onset time. The new guidelines recommend patients who meet the criteria of the DAWN or DEFUSE 3 trial should undergo mechanical thrombectomy if symptoms started in the last 6 to 16 hours (Class IA recommendation). The new guideline also states it is reasonable to consider mechanical thrombectomy for patients meeting the trial criteria and presenting with symptoms up to 24 hours (Class IIa B-R recommendation). According to these recommendations, the eligibility criteria from the DAWN and DEFUSE 3 trial should be used to determine which patients are candidates for treatment. Stent retrievers_—which use a removable mesh stent to trap and remove the clot—_are the recommended tool for mechanical thrombectomy. Expanding the treatment window to up to 24 hours allows clinicians to offer treatment to a new population who otherwise would not have options.

As these guidelines usher in a new frontier of treatment, it is a thrilling time in stroke care. In the changing landscape, patients now have additional options for treatment. These changes will increase the number of ischemic stroke patients who can be treated, providing hope to patients, families and clinicians. This is a critical step in decreasing the death and disability associated with stroke.

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