Management of Ischemic Stroke in Geriatric Patients: Anticoagulation Therapy
Immediately following an acute ischemic stroke, up to 5% of early deaths may be associated with deep venous thrombosis (DVT) or pulmonary embolism (PE). In addition, the NINDS Stroke Data Bank estimated that 30% of neurological worsening of stroke patients during hospitalization occurs in those with atherosclerotic etiologic factors. Therefore, theoretical advantages for anticoagu-lation therapy have been proposed following ischemic strokes, but its general use should be initiated cautiously. Clinical trials evaluating anticoagulation for acute ischemic stroke did not result in significant improvement in primary outcomes, reduced mortality, or prevention of recurrent stroke and revealed a modest but significantly increased risk of hemorrhage.
Trials have assessed the adjunctive use of heparin and low-molecular-weight heparin for 7 to 14 days following a stroke (Table 3). Safety and efficacy parameters consisted of stroke recurrence and rates of ICH between groups. The rates of recurrent stroke during emergent anticoagulation varied dramatically among studies. The rate of stroke recurrence was equal (1.1%) between treatment and control groups in the Trial of Org10172 in Acute Stroke Treatment (TOAST), although higher rates were observed in treated patients during the Heparin in Acute Embolic Stroke Trial (HAEST) (8.5°% vs. 7.5°%) and the Tinzaparin in Acute Ischemic Stroke Trial (TAIST) (4.7% vs. 3.1%). In studies showing reduced stroke rates with anticoagulation therapy, between 36 and 166 patients needed to receive antico-agulation to prevent one stroke recurrence. canadian antibiotics
Table 3 Use of Anticoagulants in Acute Ischemic Stroke
|Sanofi-Synthelabo SA France)|
|Pharmacia & Upjohn)|
|(not available in U.S.)||
|* The follow-up FISS-bis study reported intracranial hemorrhage at a rate of 3.7%. ** nr = not reported.
FISS = low-molecular-weight heparins; IST = International Stroke Trial; TOAST = Trial of OrgI0I72 in Acute Stroke Treatment; HAEST = Heparin in Acute Embolic Stroke Trial; TOPAS = Therapy of Patients with Acute Stroke; TASIT = Tinzaparin in Acute Ischemic Stroke.
Data from Adams HP. Stroke 2002;33:856-86Ij5
Anticoagulants appear to reduce the risk of DVT and PE. In an analysis of 10 trials evaluating anticoagulation therapy in acute stroke, the incidence of DVT and PE was reduced by 80% and 58%, respectively. In the five studies evaluating mortality rates, only one demonstrated mortality benefits over the control group. The FISS trial demonstrated that one life could be saved for every 45 individuals treated with emergent anticoagulation.
Besides the FISS trial, which noted no episodes of serious ICH, the remaining studies that evaluated anticoagulation showed rates of ICH ranging from 0.6% to 3.7% for low-dose administration. These results indicate that for every 50 to 250 individuals receiving adjunctive anticoagulation therapy for acute stroke, approximately one individual would experience a significant ICH. These studies were conducted in patients with mean ages ranging from 63 to 80 years; however, age-specific differences were not identified.
Oral anticoagulation with warfarin has not demonstrated benefit in large trials during acute management of ischemic stroke. Generally, warfarin is not a first-line treatment for secondary prevention because of the availability of safer alternative agents with similar efficacy profiles and fewer complications. The exception would be the patient with atrial fibrillation, the most common cause of cardiac embolism. Usually, oral anticoagulant therapy is the treatment of choice for secondary prevention of cardioembolic stroke and for patients with strokes of atherosclerotic origin but with contraindications to antiplatelet therapies. However, clinicians may be hesitant to use warfarin in elderly patients with atrial fibrillation despite specific practice guidelines recommending use in patients older than 75 years of age. This reluctance is often related to the perceived risk of bleeding complications associated with falls or excessive anticoagulation. Also, warfarin should be initiated at anticipated maintenance doses instead of at loading doses in order to reduce the risk of significant bleeding complications.
Most recently, the Warfarin-Aspirin Recurrent Stroke Study (WARSS) compared the effects of anticoagulation and aspirin in patients with a history of noncardioembolic stroke for secondary prevention. No statistical differences were noted in the prevention of recurrent stroke, death, or ICH; compared with warfarin, however, aspirin was associated with fewer side effects and a reduced risk of bleeding.
Because most cerebral clots are composed of fibrin and platelet aggregates, antiplatelet therapy plays a vital role in the treatment and secondary prevention of stroke. Aspirin should be initiated within 48 hours of stroke symptoms in patients with acute ischemic stroke who are not candidates for thrombolytic or anticoagulation therapy. This recommendation is based partly on the International Stroke Trial (IST) and the Chinese Acute Stroke Trial (CAST), which collectively enrolled more than 40,000 geriatric patients and determined that nine deaths or recurrences of nonfatal stroke would be prevented for every 1,000 acute stroke patients treated with aspirin.
Currently, four antiplatelet choices have been evaluated for secondary prevention of noncardioembolic stroke and TIA:
- (Hoffman-LaRoche, Inc.)
- clopidogrel canadian (Sanofi-Synthelabo, Inc.)
- dipyridamole plus aspirin (Boehringer-Ingelheim)
However, no studies have directly compared the safety and efficacy of all aspirin alternatives. Because the mechanisms of action are different among agents, one agent might offer benefit when the initial choice for therapy fails to prevent stroke. Aspirin is a first-line therapy based on its efficacy, safety, and cost.