Anticoagulation: Should It Remain Standard Therapy After Cardioembolic Stroke?

How safe is heparin for patients with embolic stroke secondary to atrial fibrillation?

Ischemic infarcts of the brain are usually caused by vascular disease, but 1 in 5 results from emboli that arise in the heart. The largest contributor to cardioembolic stroke is non-valvular atrial fibrillation, which is associated with a 5-fold increased risk of cerebral infarction. Elderly persons are at highest risk: among those older than 85 years, 1 of every 4 strokes directly results from atrial fibrillation.¹

Much attention has been given to the treatment of strokes in general and, more specifically, to early diagnosis, referral, and administration of thrombolytic therapy. However, embolic strokes merit special consideration. Because the risk of another stroke occurring within 2 weeks of the first embolic stroke is increased when the cause is atrial fibrillation, the accepted treatment has been therapeutic (not prophylactic) doses of an anticoagulant, usually heparin. Yet, evidence-based medicine has not unequivocally shown that this is the best approach.

INSIGHTS FROM A RECENT META-ANALYSIS

Paciaroni and coworkers¹ conducted a meta-analysis of randomized trials to determine whether therapeutic anticoagulation is safe and effective for patients who have had a cardioembolic stroke caused by non-valvular atrial fibrillation. Seven studies were included; 5 were blinded. Both fractionated and unfractionated heparin were represented in the meta-analysis, and anticoagulant therapy was begun early (ie, no later than 48 hours after the CNS event). Some disturbing conclusions can be drawn from the data, and they challenge the entrenchment of anticoagulation as accepted therapy for cardioembolic strokes.

Hemorrhage. CNS bleeding was a serious complication of heparin anticoagulation for embolic stroke. In one study, the likelihood of a hemorrhage was 3.28 times greater than with aspirin therapy, and 7.66 times greater than with placebo. Furthermore, heparin anticoagulation as primary therapy for embolic stroke did not reduce the end points of death and disability.

Thrombotic complications. Patients who have sustained a cerebral infarction are at high risk for thrombotic complications, such as deep venous thrombosis and pulmonary embolism, during their hospitalization. In one study, fewer pulmonary emboli occurred in patients treated with therapeutic doses of unfractionated heparin during recovery from stroke than in those who did not receive heparin (0.5% vs 0.8%).² However, after 6 months, the rates of pulmonary embolism were the same in patients who received only aspirin as in those who had been given heparin.

IMPLICATIONS FOR TREATMENT OF CARDIOEMBOLIC STROKES

Paciaroni and colleagues¹ concluded that the therapeutic administration of either fractionated or unfractionated heparin did not reduce death or disability resulting from cardioembolic strokes. This was the case even when heparin was given early in the course of the CNS event. Because the most devastating outcome in the heparin treatment groups was a CNS hemorrhage, caution is strongly advised.

References:

REFERENCES:

1.

Paciaroni M, Agnelli G, Micheli S, Caso V. Efficacy and safety of anticoagu- lant treatment in acute cardioembolic stroke: a meta-analysis of randomized controlled trials.

Stroke

. 2007;38:423-430.

2.

Saxena R, Lewis S, Berge E, et al. Risk of early death and recurrent stroke and effect of heparin in 3169 patients with acute ischemic stroke and atrial fibrillation in the International Stroke Trial.

Stroke

. 2001;32:2333-2337.