Safety and Efficacy of Mechanical Thrombectomy Utilizing Reversal Flow

BACKGROUND Stroke is an acute injury to the brain with a vascular cause that results in permanent neuronal injury and functional disability. Stroke can be divided into two subtypes: ischemic and hemorrhagic. Ischemic strokes occur when an occlusion (i.e., blockage of blood vessel) or flow-limiting stenosis of cerebral vessels (i.e., narrowing of an artery in the brain) cause inadequate blood flow for neuronal sustainment. They are caused by cerebral small vessel disease, cardioembolism, and large artery disease. Hemorrhagic strokes typically result from a rupture caused by an aneurysm or other non-traumatic causes (e.g., chronic hypertension) and from illicit drug abuse.

Globally, stroke is the second leading cause of both death and disability. In 2016, worldwide prevalence was 80.1 million, and slightly higher among women (41.1 million) than in men (39.0 million). The incidence of new strokes globally in 2016 was 13.7 million. In the United States, stroke is the fifth-leading cause of death and a major cause of severe disability, as well as the primary cause of hospitalization for neurologic disease. Within the US, the prevalence of stroke is approximately 3% in adults 20 years or older, translating to approximately 7 million occurrences of stroke within this population. Of all strokes, approximately 87% are ischemic. In 2017, the global incidence of ischemic strokes was 101.3 per 100,000 people.

Certain factors, both modifiable and non-modifiable, can increase an individual's likelihood of stroke. The most prominent non-modifiable risk factor is age. Incidence doubles for each decade after the age of 55, increasing the risk for individuals within this age group. Other key non-modifiable risk factors include sex, ethnicity, and genetics. The most important modifiable risk factor for stroke is hypertension. Elevated blood pressure increases the risk of stroke; half of all stroke patients have a history of hypertension. Other notable modifiable risk factors include diabetes mellitus, cardiac factors (e.g., atrial fibrillation), smoking, high alcohol consumption, substance abuse, obesity, and inflammation.

Stroke can have a monumental effect on many areas of life, both individually and globally. Stroke survivors develop physical impairments which can limit daily living, as well as communication skills. Additionally, approximately 80% of the stroke population experience cognitive impairments, which has a sizeable effect on an individual's ability to complete daily tasks. Physical consequences of stroke can impede survivors from participating in work or other activities that were at one point an essential part of their identity. Aside from physical effects, stroke can also greatly impact one's mental state. Additionally, variations in communication skills caused by stroke have a profound effect on self-confidence. As a result, stroke survivors engage in less social activities, causing a substantial vulnerability to their social networks. Furthermore, the economic burden associated with stroke is vast, with the 2019 global value of lost welfare due to stroke being $2059.67 billion. Addressing stroke care and developing new targeted approaches to aid in stroke treatment can have a lasting benefit not only to the individual, but also worldwide.

Reperfusion therapy can be used to treat ischemic stroke, as it allows for the restoration of blood flow to salvageable brain tissue. Reperfusion therapy has two main components: thrombolysis, including intravenous (IV) tissue plasminogen activator (tPA), and endovascular interventions such as mechanical thrombectomy. The two components of reperfusion therapy, thrombolysis and endovascular interventions, can be used separately or in tandem. Thrombolysis is a pharmacological treatment to dissolve blood clots using an infusion of tPA, known as alteplase. The only FDA-approved IV thrombolytic agent for the treatment of an ischemic stroke is alteplase, yet off-label IV tenecteplase, a genetically modified form of alteplase given as a single bolus, is beginning to be used more regularly. Some guidelines have recommended either alteplase or tenecteplase for patients with acute ischemic stroke within 4.5 hours after known onset. It is crucial to deliver IV thrombolysis expeditiously, as the number needed to treat for favorable outcome almost double from 5 (for treatment within 90 min) to 9 (when given at 3-4.5 hours). However, the benefits of IV tPA varies among those with severe stroke caused by large artery occlusion due to an inability to achieve early recanalization (i.e., restoration of blood flow). Significant independent risk factors predicting poor outcomes post IV-thrombolysis are length and location of the arterial thrombus (i.e., blood clot). Therefore, this lack of efficacy of what was once the only treatment for stroke led to efforts to remove larger arterial thrombi using intra-arterial techniques by mechanical thrombectomy, the other component of reperfusion therapy.