Vertebrobasilar Atherothrombotic Disease Medication
- Author: Eddy S Lang, MDCM, CCFP(EM), CSPQ; Chief Editor: Robert E O'Connor, MD, MPH more...
Antiplatelet medications constitute first-line treatment for patients with vertebrobasilar atherothrombotic disease (VBATD). This approach is supported by a large body of clinical research in the secondary prevention of strokes, and although benefits are small, its application to posterior circulation events is well established.
Important inferences can be drawn from the European Stroke Prevention Study, which examined the efficacy of a daily regimen of 225 mg of dipyridamole and 990 mg of aspirin in 2500 patients randomized to receive drug therapy or placebo. The overall total incidence of stroke or death (the end points) during the 2-year follow-up in the placebo group was lower in the vertebrobasilar group compared to the carotid group (14% versus 24%, respectively). The combination therapy of dipyridamole and acetylsalicylic acid caused a marked reduction in the incidence of stroke or death in patients with vertebrobasilar (51%) and carotid (30%) events. When only stroke was considered as the end point, dipyridamole and acetylsalicylic acid seemed to be more effective in reducing the risk of transient ischemic attacks than stroke, and more effective in men than in women.
No randomized clinical trials have been conducted to determine antiplatelet therapy's efficacy in treating VBATD. Antiplatelet therapy's widely perceived benefits for cerebrovascular disease may prevent an ethically acceptable trial with a placebo arm.
Data from the International Stroke Trial (IST) revealed a small but real clinical benefit of antiplatelet therapy in patients who experienced a completed stroke. The IST results suggest that only 1% of patients may benefit from aspirin therapy.
Arguments for anticoagulant therapy in VBATD are much more tenuous. A nonrandomized, concurrent, cohort study suggested that anticoagulation provided superior stroke protection for patients with vertebrobasilar TIAs than for patients with carotid TIAs. No randomized clinical trials involving patients with vertebrobasilar TIAs have compared anticoagulants to antiplatelet therapy or to placebos.
A strong argument favoring use of anticoagulants in VBATD includes settings in which the embolic source of thrombi is known or suspected (eg, atrial fibrillation).
Use of low-molecular-weight heparins has shown no significant improvement in outcome over conventional treatments.
Very little evidence from well-powered RCTs supports using intravenous administered thrombolytics to patients with posterior circulation infarcts. A single study of 883 patients comparing anterior circulation strokes (ACS) and posterior circulation strokes (PCS) suggested that PCS had lower symptomatic intracranial hemorrhage frequency following intravenous thrombolysis. Although, favorable outcomes and mortality were both similar between the ACS and PCS patients. All thrombolytics are plasminogen activators and act either directly (urokinase, alteplase) or indirectly (streptokinase).
Use of an intra-arterial thrombolytic is also supported by some experts for those patients within 6 hours of stroke onset who do not qualify for IV thrombolytics.
The incidence of intracerebral hemorrhage as a complication of treatment was apparently 10%, similar to rates seen in stroke trials using systemic thrombolysis.
These agents prevent recurrent or ongoing thromboembolic occlusion of the vertebrobasilar circulation.
Augments activity of antithrombin III and prevents conversion of fibrinogen to fibrin. Does not actively lyse yet is able to inhibit further thrombogenesis. Prevents reaccumulation of clots after spontaneous fibrinolysis.
Interferes with hepatic synthesis of vitamin K-dependent coagulation factors. Used for prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders. Tailor dose to maintain INR in range of 2-3.
These agents inhibit the cyclooxygenase system, decreasing the level of thromboxane A2, which is a potent platelet activator.
Inhibits prostaglandin synthesis, which prevents formation of platelet-aggregating thromboxane A2. Studies report 300 mg/d dose as effective as larger dose and may be associated with fewer adverse effects.
Second-line antiplatelet therapy for patients who cannot tolerate aspirin or in whom aspirin is ineffective.
Inhibits platelet aggregation by inhibiting binding of ADP to platelet receptor and subsequent ADP-mediated activation of glycoprotein GPIIb/IIIa complex. Rapidly absorbed from GI tract. Used as second-line therapy for patients with TIA crescendo symptoms who are already taking aspirin.
These agents restore perfusion in the infarct-related artery.
Tissue plasminogen activator exerts effect on fibrinolytic system to convert plasminogen to plasmin. Plasmin degrades fibrin, fibrinogen, and procoagulant factors V and VIII. Serum half-life is 4-6 min but half-life lengthened when bound to fibrin in clot. Used in management of acute myocardial infarction (MI), acute ischemic stroke, and pulmonary embolism (PE). Heparin and aspirin are not given for 24 h after tPA. Must be given within 3 h of stroke onset. Exclude hemorrhage by CT scan. If hypertensive, lower BP with labetalol, 10 mg IV. Safety and efficacy of concomitant administration with aspirin and heparin during first 24 h after onset of symptoms have not been investigated.
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