Oral anticoagulation for cerebral ischemia of arterial origin

Abstract

Article abstract-Background: The use of oral anticoagulant therapy for the prevention of arterial thromboembolism in patients who have had ischemic stroke is controversial. Coumarins may increase the bleeding risk in patients with cerebral ischemia of arterial origin. Objectives: 1) To calculate incidence rates of bleeding and thromboembolic events in patients with noncardiac cerebral ischemia who were treated routinely in an anticoagulation clinic. 2) To assess which factors contribute to the occurrence of events. 3) To determine the optimal intensity of oral anticoagulant therapy in these patients. Methode: The authors studied all patients treated for noncardiac cerebral ischemia at the Leiden anticoagulation clinic between 1993 and 1998. Outcome events were major hemorrhage, major arterial thromboembolism, and death. Results: The authors observed 356 patients for 644 patient-years. The incidence of major hemorrhage was 3.9 per 100 patient-years (95% CI, 2.5 to 5.7) and that of thromboembolism was 3.0 per 100 patient-years (95% CI, 1.8 to 4.6). The incidence of hemorrhage varied with the duration of treatment (relative risk [RR] of the first versus the second half-year, 3.8; 95% CI, 1.9 to 7.6), age (RR for age >65 years, 3.7; 95% CI, 1.1 to 12.3), and the intensity of oral anticoagulation (RR, 1.8 for each 0.5 international normalized ratio [INR] unit increase; 95% CI, 1.5 to 2.3). The optimal intensity of oral anticoagulant therapy was 2.5 to 3.5 INR; the best target value was 3.0 INR. Conclusion. The risk of hemorrhage with anticoagulant therapy is high in patients with ischemic stroke of arterial origin but is mainly confined to early use and elderly patients. NEUROLOGY 2001;57· 1993-1999 Patients with atrial fibrillation 1 or myocardial infarction 2 4 benefit from treatment with coumarins; however, treatment introduces a moderate annual bleeding risk of 2% to 3%. A study of coumarins in patients with atrial fibrillation and recent nondisabling cerebral ischemia showed a 65% reduction of recurrent strokes with an accompanying annual bleeding risk of less than 3% percent. 5 These results suggest that oral anticoagulation may prevent stroke in a wider ränge of indications.To investigate whether coumarins also could improve the outcome for patients with stroke of noncardiac origin, the Stroke Prevention in Reversible Ischemia Trial (SPIRIT) was designed. SPIRIT was an open, multicenter clinical trial in which patients with cerebral ischemia of presumed arterial origin were randomized between low-dose aspirin (30 mg daily) and full-dose anticoagulation (international normalized ratio [INR], 3.0 to 4.5). 6 The trial was prematurely terminated after the first interim analysis revealed an excessive rate of bleeding complications (7% per year) in patients randomized to oral anticoagulation. Subsequent analyses revealed differences between patients that might help to explain the observed risks; high INR levels äs well äs the presence of leukoaraiosis appeared to be related to the bleeding risk in particular. 6 7 ...

Anticoagulation intensity and outcomes among patients prescribed oral anticoagulant therapy: a systematic review and meta-analysis

“…We included 19 studies published between 1992 and 2007 in our analysis 6,[21][22][23][24][25][26][27][28][29][32][33][34][35][36][37][38][39][40] (Table 1). Of these, 14 reported both hemorrhagic and thromboembolic events, 6,21,23,25,[27][28][29][32][33][34][35][36][37]39 3 reported only hemorrhagic events, 22,38,40 and 2 reported only thromboembolic events.…”

“…Of these, 14 reported both hemorrhagic and thromboembolic events, 6,21,23,25,[27][28][29][32][33][34][35][36][37]39 3 reported only hemorrhagic events, 22,38,40 and 2 reported only thromboembolic events. 24,26 Half were retrospective cohort studies and two-thirds (68%) were community-based studies.…”

“…6,[21][22][23][32][33][34][35][36][37][38][39][40] The remaining studies reported ranges that fit only into 3 categories because their maximum range was a ratio greater than 3. [24][25][26][27][28][29] Studies differed in the methods used to identify hemorrhagic and thromboembolic events and assign them to ranges of international normalized ratios.…”

“…[24][25][26][27][28][29] Studies differed in the methods used to identify hemorrhagic and thromboembolic events and assign them to ranges of international normalized ratios. To identify events, 12 studies used follow-up visits, 23,[25][26][27][28][32][33][34][36][37][38][39] 4 used medical record review alone, 24,29,35,40 and 3 used administrative databases, including those for billing claims, 21 discharge abstracts 6 and deaths. 22 To assign events to a range, 4 studies used only ratios measured at the time of the event.…”

“…22,24,28,39 If ratios at the time of the events were unavailable, 15 studies assigned events to a range using previous measurements, taken from 2 days 32 to as many as 28 days 36,39 before the event. 6,21,23,25,26,29,[32][33][34][35][36][37][38][39][40] Half of the studies excluded at least one event because they could not be assigned to a range.…”