Stroke

Treatment and management

Stroke unit care¹

Stroke unit care is the prerequisite foundation on which more complex acute interventions are built. One key aspect of stroke unit care is the targeting of secondary prevention strategies based on an understanding of stroke mechanism¹.

Antiplatelet therapy ¹

Aspirin given acutely within 48 hours reduces the risk of recurrent stroke and improves outcome. The benefit is smaller than with reperfusion therapies, but aspirin is widely applicable and inexpensive¹.

Reperfusion therapies¹

• Intravenous thrombolysis¹
  Two main drugs are available for intravenous thrombolysis: alteplase and tenecteplase. Alteplase is a recombinant form of tissue plasminogen activator (tPA), which cleaves plasminogen to plasmin. Plasmin then degrades fibrin and dissolves the thrombus. Plasmin is rapidly inactivated by antiplasmin and, therefore, has a short half-life outside the thrombus. Accordingly, alteplase is administered as an initial bolus followed by a 1 hour infusion. This therapy is considered the standard thrombolytic and is globally licensed for ischemic stroke¹.
• Endovascular thrombectomy¹
  Initial guidelines for endovascular thrombectomy recommended treatment within 6 hours of stroke onset. However, the more recent trials demonstrated a major benefit of reperfusion up to 24 hours after onset, provided advanced brain imaging indicates the presence of salvageable brain tissue. In general, endovascular thrombectomy has few contradictions in patients with a suitable large artery occlusion target and good premorbid function. Patients who are ineligible for intravenous thrombolysis due to a risk of systemic bleeding can be treated with endovascular thrombectomy¹.

Acute treatments for intracerebral hemorrhage²

Antihypertensive treatment²

Other than care in a stroke unit, intensive lowering of blood pressure at an early stage to approximately 140 mm Hg systolic is the only evidence-based treatment for intracerebral hemorrhage. Although pooled as-treated analysis showed improved outcomes with a reduction to 120 mm Hg, this result could have been confounded by incomplete adjustment of prognostic variables.²

Antithrombotic treatment²

Reversal of antithrombotic medications is another acute treatment for intracerebral hemorrhage. The effects of warfarin can be reversed with prothrombin factor concentrate and vitamin K. Unfractionated heparin can be reversed with protamine. Dabigatran can be reversed almost instantaneously with idarucizumab, and low molecular weight heparin and the anti-Xa direct oral anticoagulants apixaban and rivaroxaban can be reversed using andexanet alfa².

Acute treatments for ischemic stroke^2,3

Antihypertensive treatment³

The protocols for the thrombolytic trials instructed that blood pressure should be controlled to below 180/105 mm Hg after thrombolytic treatment. Most patients enrolled in mechanical thrombectomy trials were also eligible for and treated with intravenous alteplase, so blood pressure was controlled as per post-alteplase guidelines (<180 /105 mm Hg). Debate remains regarding whether blood pressure should be lowered further post-thrombectomy if reperfusion is achieved. The DAWN trial protocol recommended systolic pressure below 140 mm Hg for 24 hours after reperfusion ³.

Thrombolytic treatment²

Intravenous thrombolysis with recombinant human tPA (alteplase) aims to reperfuse the ischemic brain by converting plasminogen (PLG) to plasmin, which can dissolve the thrombus that is causing the stroke. When alteplase is delivered within 3 hours of onset, approximately one in four patients have reduced disability, which decreases to one in seven patients between 3 hours and 4.5 hours. This benefit includes the effect of the approximately 2% absolute risk of fatal intracerebral hemorrhage. Tenecteplase is a genetically modified form of alteplase that has a longer half-life, permitting a single bolus administration (rather than bolus and 1 hour infusion of alteplase) and greater fibrin specificity and resistance to plasminogen activator inhibitors than does alteplase ².

Secondary prevention^1,3

The prevention of recurrent stroke requires a combination of standard strategies and targeted interventions and, in some patients, depends on stroke etiology. Lifestyle risk factors for stroke include smoking, excessive salt intake, obesity and physical inactivity, which are similar to the risk factors for other cardiovascular diseases¹.

Management has two main objectives when patients present with acute ischemic stroke or transient ischemic attack (TIA): to minimize disability from the acute event and decrease the likelihood of another stroke. The risk of recurrent stroke is highest soon after presentation, when presumably the factors leading to the current event are still in play. Therefore, secondary stroke prevention strategies will be most successful if implemented as soon as possible³.

Antiplatelet therapies¹

Antiplatelet therapies (such as aspirin, clopidogrel and aspirin–dipyridamole) are the main antithrombotic used after ischemic stroke. Clopidogrel has a small absolute risk reduction benefit compared with aspirin, although aspirin is still commonly prescribed as first-line therapy because it is inexpensive and widely available¹.

Replacement of Warfarin¹

Antiplatelet therapy is not effective for all patients who require anticoagulation, such as those with atrial fibrillation. Direct oral anticoagulants have largely replaced warfarin in these patients owing to convenience and reduced intracerebral hemorrhage risk, provided creatinine clearance is adequate to excrete these medications and there is no mechanical prosthetic valve or moderate–severe mitral stenosis.

Specific reversal agents now exist, such as idarucizumab for dabigatran, which is widely available, and andexanet alfa for apixaban and rivaroxaban, which is FDA approved and increasingly available. This improves safety in the event of trauma or a requirement for emergency surgery. In patients taking dabigatran who present with ischemic stroke, case series have shown that reversal with idarucizumab can be safely followed by thrombolysis¹.

Underutilize anticoagulation in atrial fibrillation patient¹

A role for percutaneous left atrial appendage occlusion in patients with a genuine contraindication to anticoagulation is emerging. However, anticoagulation is generally underutilized in patients with atrial fibrillation and often underdosed due to misperceptions about risk versus benefit, leading to unnecessary recurrent ischemic strokes ¹.

Prevention of complications¹

Patients with ischemic stroke are at particularly high risk of deep venous thrombosis and pulmonary embolism. Pharmacological prophylaxis with low-molecular-weight heparin and/or intermittent pneumatic compression devices reduces the risk of venous thromboembolism. Standard compression stockings are not effective. Venous thromboembolic prophylaxis is recommended in guidelines for all immobile patients with stroke. In addition, aspiration pneumonia associated with dysphagia (difficulty swallowing) is a common complication in patients with ischemic stroke. Carrying out a validated swallow screen is, therefore, essential before the oral administration of medications, food and drink¹.