What is the optimal pharmacological prophylaxis for the prevention of deep-vein thrombosis and pulmonary embolism in patients with acute ischemic stroke?

BACKGROUND: Pulmonary embolism after acute ischemic stroke (AIS) is associated with a high in-hospital mortality. The benefit from pharmacological prophylaxis for venous thromboembolism (VTE) is uncertain probably due to doubts about the optimal agent and dose. We evaluated the benefit/risk ratio of different anticoagulant regimens in the prevention of VTE in patients with AIS.
METHODS: The MEDLINE, EMBASE, and Cochrane Library databases were searched up to January 2005. Randomized controlled trials (RCT) comparing early administration of either low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) with control were included. Endpoints were objectively diagnosed deep-vein thrombosis (DVT), pulmonary embolism, intracranial hemorrhage (ICH), and extracranial hemorrhage (ECH). Low-dose UFH was arbitrarily defined as < or =15,000 IU/day, low-dose LMWH as < or =6000 IU/day or weight-adjusted dose of < or =86 IU/kg/day.
RESULTS: Sixteen trials involving 23,043 patients with AIS met the inclusion criteria. The number of events was small and different doses of anticoagulant treatment were used. Compared to control, high-dose UFH was associated with a reduction in pulmonary embolism (OR=0.49, 95% confidence interval (CI)=0.29-0.83), but also with an increased risk of ICH (OR=3.86, 95% CI=2.41-6.19) and ECH (OR=4.74, 95% CI=2.88-7.78). Low-dose UFH decreased the thrombosis risk (OR=0.17, 95% CI=0.11-0.26), but had no influence on pulmonary embolism (OR=0.83, 95% CI=0.53-1.31); the risk of ICH or ECH was not statistically significant increased (OR=1.67, 95% CI=0.97-2.87 for ICH; and OR=1.58, 95% CI=0.89-2.81 for ECH, respectively). High-dose LMWH decreased both DVT (OR=0.07, 95% CI=0.02-0.29) and pulmonary embolism (0.44, 95% CI=0.18-1.11), but this benefit was offset by an increased risk for ICH (OR=2.01, 95% CI=1.02-3.96) and ECH (OR=1.78, 95% CI=0.99-3.17). Low-dose LMWH reduced the incidence of both DVT (OR=0.34, 95% CI=0.19-0.59) and pulmonary embolism (OR=0.36, 95% CI=0.15-0.87), without an increased risk of ICH (OR=1.39, 95% CI=0.53-3.67) or ECH (OR=1.44, 95% CI=0.13-16). For low-dose LMWH, the numbers needed to treat were 7 and 38 for DVT and pulmonary embolism, respectively.
CONCLUSIONS: Indirect comparison of low and high doses of UFH and LMWH suggests that low-dose LMWH have the best benefit/risk ratio in patients with acute ischemic stroke by decreasing the risk of both DVT and pulmonary embolism, without a clear increase in ICH or ECH.