PREvention of VENous Thromboembolism in Hemorrhagic Stroke Patients – PREVENTIHS Study: A Randomized Controlled Trial and a Systematic Review and Meta-Analysis

Abstract

<b><i>Background:</i></b> In this randomized trial, currently utilized standard treatments were compared with enoxaparin for the prevention of venous thromboembolism (VTE) in patients with intracerebral hemorrhage (ICH). <b><i>Methods:</i></b> Enoxaparin (0.4 mg daily for 10 days) was started after 72 h from the onset of ICH. The primary outcome was symptomatic or asymptomatic deep venous thrombosis as assessed by ultrasound at the end of study treatment. The safety of enoxaparin was also assessed. We included the results of this study in a meta-analysis of all relevant studies comparing anticoagulants with standard treatments or placebo. <b><i>Results:</i></b> PREVENTIHS was prematurely stopped after the randomization of 73 patients, due to the low recruitment rate. The prevalence of any VTE at 10 days was 15.8% in the enoxaparin group and 20.0% in the control group (RR 0.79 [95% CI 0.29–2.12]); 2.6% of enoxaparin and 8.6% of standard therapy patients had severe bleedings (RR 0.31 [95% CI 0.03–2.82]). When these results were meta-analyzed with the results of the selected studies (4,609 patients; 194 from randomized trials), anticoagulants were associated with a nonsignificant reduction in any VTE (OR 0.81; 95% CI 0.43–1.51), in pulmonary embolism (OR 0.53; 95% CI, 0.17–1.60), and in mortality (OR 0.85; 95% CI 0.64–1.12) without increase in hematoma enlargement (OR 0.97; 95% CI, 0.31–3.04). <b><i>Conclusions:</i></b> In patients with acute ICH, the use of anticoagulants to prevent VTE was safe but the overall level of evidence was low due to the low number of patients included in randomized clinical trials.