PURPOSE: Venous thromboembolism (VTE) remains a common complication following stroke, but the optimal pharmacologic prophylaxis for these patients remains unclear. To clarify this issue we conducted a meta-analysis of studies comparing low-molecular weight heparin (LMWH) to unfractionated heparin (UF) for VTE prophylaxis following stroke.
METHODS: We identified randomized trials of LMWH vs. UFH for VTE prevention in acute stroke patients. We excluded non-randomized studies and tirals which compared pharmacologic intervention to placebo. We evaluated these trials as to their quality and extracted rates of VTE, proximal deep vein thrombosis (DVT), and pulmonary embolism (PE). We also recorded rates of major bleeding and intracerebral hemorrhage (ICH).
RESULTS: We identified 3 randomized trials (total n=2028). Two protocols were double-blinded. Enoxaparin (40 mg daily) was used in two reports while one employed certoparin (3000 anti-Xa IU daily). UFH (5000u) was given three times daily in only one trial while it was used three times daily in the others. The quality of the studies was generally high (median Jdad score 6). Overall severity of illness was similar between the UFH and LMWH arms, and most patients had suffered debilitating strokes. LMWH was associated with an approximate 50% reduction in the rate of any VTE (OR: 0.54, 95%CI: 0.22-0.97,p<0.001). The incidence of proximal DVT was reduced to the same degree (OR: 0.53, 95% CI: 0.37-0.76,p<0.001), while there a greater impact on preventing PE with LMWH(OR: 0.24, 95% CI: 0.06-0.97,p<0.001). There was no difference in the frequency of major bleeding or ICH between LMWH and UFH. Restricting the analysis to only the studies using enoxaparin did not alter our findings.
CONCLUSION: VTE appears common in persons with acute stroke. LMWHs, relative to UFH, significantly reduce the risk for VTE and, more importantly, for PE. LMWHs are not associated with an increased risk for major bleeding or ICH in stroke patients.
CLINICAL IMPLICATIONS: Given the difficulties in both the diagnosis and management of VTE following stroke, physicians should consider broader use of LMWH in this setting.
DISCLOSURE: Andrew Shorr, No Product/Research Disclosure Information; Grant monies (from industry related sources) Prior studies supported by GSK and Sanofi-Aventis. However, no support was provied for this project; Consultant fee, speaker bureau, advisory committee, etc. GSK, Sanofi Aventis