Stroke is the second leading cause of death worldwide, with approximately 60% of affected people suffering from a variable residual disability. This requires institutional care within 3 months in 20% of cases. In addition, stroke is related to an increased risk of immediate comorbidities such as deep vein thrombosis, ab ingestis
pneumonia, and such long-term problems as dementia and cognitive decline.
The most significant therapies are drugs that inhibit platelet function. These drugs are widely used to decrease the risk of occlusive arterial events in patients with atherosclerosis and include the following:
- Cyclooxygenase-1 (COX-1) inhibitors, such as aspirin
- Adenosine phosphate (ADP) receptor antagonists, such as the thienopyridine compounds ticlopidine and clopidogrel
- Glycoprotein IIb/IIIa antagonists
Both aspirin and the thienopyridines selectively inhibit a single pathway of platelet activation: aspirin affects the arachidonate-thromboxane pathway, while the thienopyridines affect the ADP pathway by irreversibly blocking the ADP receptor P2Y12
. The antithrombotic efficacy of these drugs, despite their selective mechanism of action, is explained by the fact that both the arachidonate-thromboxane pathway and the ADP pathway contribute to the amplification of platelet activation and are essential for the full aggregation response of platelets under several experimental conditions.
Cardioembolism is considered responsible for 20 to 25% of strokes, but the exact proportion is unknown because of concurrence of cerebral atherosclerotic lesions. The most important therapy relies on anticoagulant drugs. Anticoagulant therapy plays a major role in the treatment of patients with neurological illness, primarily those with cerebrovascular disease.
Anticoagulant therapy can be used in the setting of acute cerebral ischemia with a goal of improving and maintaining cerebral blood flow. In this setting, it may be used to prevent reocclusion of vessels that has recanalized, either spontaneously via the body’s own intrinsic fibrinolytic mechanisms or following either pharmacological or mechanical thrombolytic therapy. It may also be used to stop thrombus propagation in partially occluded vessels and to maintain patency of collateral vessels, particularly those with sluggish flow. Anticoagulant therapy may be used to prevent secondary recurrent events, either in the acute period or on a long-term basis. These events may be due to (1) embolization from a proximal source, such as the heart, aorta, or large vessels; (2) spontaneous thrombosis from a hypercoagulable state; or (3) vessel occlusion due to rupture of an atherosclerotic plaque and subsequent local thrombosis. In addition, anticoagulant therapy may be used to prevent or treat the complications of deep vein thrombosis and pulmonary embolism resulting from immobility related to brain injury and ensuing paralysis.
Anticoagulants have a number of disadvantages that limit their use, such as a narrow therapeutic index, the need for frequent monitoring and at times complex dose adjustments, and multiple interactions with food and other medications. Many of these limitations are magnified in the neurological population, who are often elderly, may have an increased prevalence of cognitive impairment due to prior stroke, and may have difficulty with obtaining health services due to limited mobility.