Anticoagulants, stroke

Gage BF, van Walraven C, Pearce LA et al. (2004). Selecting patients with atrial fibrillation for anticoagulation. Stroke risk stratification in patients taking aspirin. Circulation 110 2287-2292 Giles MF, Rothwell PM (2007). Risk of stroke early after transient ischaemic attack a systematic review and meta-analysis. Lancet Neurology 6 1063-1072... 

Some examples of this approach are the linkage of adverse outcomes of inappropriate anticoagulation (stroke, myocardial infarct, or death widiin 6 days) to the measurement of prothrombin times and the linkage of adverse effects of digoxin therapy (death or hospitalization caused by insufficiency, overdose, or drug reaction) with the measurement of digoxmd ... 

Coumarin is also widely used for long-term anticoagulation in chronic atrial fibrillation (particularly to avoid cardioembolic strokes), to prevent DVT or PE in patients with chronic hypercoagulability (e.g., congenital AT or protein C deficiency), or to prevent... 

INR > 1.7 (PT > 15 if no INR available) with or without chronic oral anticoagulant use Seizure at onset of stroke (This relative contraindication is intended to prevent treatment of patients with a deficit due to postictal Todd s paralysis or with seizure due to some other CNS lesion that precludes thrombolytic therapy. If rapid diagnosis of vascular occlusion can be made, treatment may be given.)... 

While early CEA is considered to be relatively safe, it may not always be necessary. For instance, early surgery can be deferred in patients who are medically unstable or for those whose cardiac or respiratory status requires optimization. In the NASCET study, the rate of ipsUateral stroke at 1 month for medically treated patients with high-grade stenoses was only 3.3% and was even lower (1.7%) in patients with near-occlusions. Even in patients with free-floating intraluminal thrombus, anticoagulant therapy is a well tolerated and reasonable first step, given... 

Combination Anticoagulant and Antiplatelet Therapy in Acute Stroke... 

The Cochrane group examined (a) whether the addition of UFH or LMWH to antiplatelet agents offers any net advantage over antiplatelet monotherapy for acute stroke, and (b) the effectiveness of anticoagulants compared to antiplatelets in acute ischemic stroke. They included 4 trials of 16,558 patients, each of which specified aspirin (160-333 mg daily) as the control, and all of which randomized patients within 14 days of stroke onset. The anticoagulants tested were UFH and LMWH. Almost 98% of the patients were followed up for 6 months. 

This was largely influenced by the high-dose UFH group in 1ST (OR 1.38, 95% Cl 1.05-1.82). An interaction by UFH dose (p = 0.01) on recurrent stroke risk with combination UFH-aspirin therapy compared to aspirin monotherapy was observed, with a trend toward increased risk of recurrent stroke with high-dose UFH + aspirin (OR 1.22, 95% Cl 0.92-1.62) and a trend toward reduced risk with low-dose UFH + aspirin (OR 0.75, 95% Cl 0.56-1.03), equivalent to 10 fewer (95% Cl 0-20 fewer) recurrent strokes per 1000 patients treated. They found a small, but significant beneht of LMWH over aspirin in the prevention of symptomatic DVT, equivalent to 10 (95% Cl 0-30) fewer DVTs per 1000 patients treated. Compared with aspirin, anticoagulants were associated with nonsignificantly fewer symptomatic PEs (OR 0.85, 95% Cl 0.55-1.32). There were fewer PEs with the combination of UEH and aspirin (OR 0.58, 95% Cl 0.34—1.00), equivalent to 5 fewer (Cl 0-10) PEs per 1000 patients treated. However, the overall incidence of symptomatic DVT and PE was low (1.1% and 0.7%). 

Overall no evidence was found to support the claim that anticoagulants offer a net advantage over aspirin in patients with acute ischemic stroke. There was evidence, however, to suggest that combination anticoagulant and aspirin therapy was associated with a small increase in the number of deaths at the end of follow-up, equivalent to 20 more deaths per 1000 patients treated. This adverse effect can probably be attributed partly to the 10 extra sICHs, and the 5 extra major extracranial hemorrhages per 1000 patients treated with combination anticoagulant/ aspirin therapy. 

Acute Anticoagulation for AF-associated Stroke HAEST and 1ST provided valuable data on relatively large numbers (449 in HAEST, 3169 in 1ST) of patients with AF-associated ischemic stroke treated with acute anticoagulation (danaparoid in HAEST, UFH in 1ST). HAEST found no reduction in early stroke recurrence or effect on late functional outcome in the LMWH arm. In contrast, 1ST found a dose-dependent reduction in early recurrence rates, but no late functional benefit associated with UFH. However, this was offset by an increase in rates of sICH among patients with AF receiving UFH, with no net benefit in the composite outcome of recurrence stroke and sICH combined. The reasons for the discrepancy between trials is unclear. 

Anticoagulation in Stroke Due to LAA Disease Few clinical trials have been performed in this population. In the TOAST trial, a secondary analysis in patients with stroke due to LAA found favorable outcomes at 7 days in 54% of danaparoid-treated patients, compared to 38% of the placebo-treated group (p = 0.02). At 3 months, 68% of patients in the danaparoid group compared to 53% of those in the placebo group had favorable outcomes (p = 0.02). 

Acute anticoagulation is widely used in the acute setting of arterial dissection. Once again, the rationale is to prevent propagation of local thrombosis and formation of new thrombus at the site of the injured arterial wall, which is beheved to reduce the likelihood of early stroke recurrence. This practice, while rational, is based on anecdotal evidence and case series, as randomized controlled trials have... 

Urgent anticoagulation is not recommended for treatment of patients with moderate-to-severe stroke because of a high risk of serious intracranial bleeding complications (grade A). 

For patients with Acute Ischemic Stroke they recommend clinicians not to use full-dose anticoagulation with IV, subcutaneous, or low-molecular-weight heparins or heparinoids (grade 2B evidence). 

Some experts recommend early anticoagulation for various specific stroke subgroups, including cardioembolic stroke, progressing stroke, stroke... 

Clinical trials have not, however, adequately evaluated adjusted-dose IV anticoagulation in these selected stroke patients. 

No trials have evaluated the role of very early anticoagulation (12 hours after stroke onset) in any stroke population. 

The Cochrane Collaboration. Anticoagulants for acute ischemic stroke 2006 [Review]. 

Berge E, Sandercock P. Anticoagulants versus antiplatelet agents for acute ischemic stroke (Review). The Cochrane Collaboration 2006. 

Evans A, Perez I, Yu G, Kalra L. Should stroke subtype influence anticoagulation decisions to prevent recurrence in stroke patients with atrial flbrillation Stroke 2001 32 2828-2832. 

Cerebral Embolism Study Group. Immediate anticoagulation of embolic stroke a randomized trial. Cerebral Embolism Study Group. Stroke 1983 14 668-676. 

Many patients have a rhythm that varies between atrial flutter and AF. Atrial flutter is associated with a 40% higher risk of stroke. Given that the concordance of the AF and atrial flutter is high, anticoagulation should be considered in patients with atrial flutter and coexisting cardiac pathology predisposing to left atrial thrombus. 

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