Abstract
Background: Venous thromboembolism (VTE) prophylaxis with low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) is recommended in acute ischemic stroke patients, but most studies comparing LMWH and UFH are limited in methodology or sample size. The PREVAIL study was designed to assess the superiority of enoxaparin over UFH for VTE prophylaxis in acute ischemic stroke patients and to evaluate efficacy and safety according to stroke severity.
Methods: Patients with acute ischemic stroke, confirmed by CT scan, and unable to walk unassisted due to motor impairment of the leg were enrolled in this prospective, open-label, parallel group, multicenter study. Patients from 15 countries were randomized within 48 h of stroke symptoms to receive enoxaparin 40 mg SC qd or UFH 5000 IU SC q12h for 10±4 days. Patients were stratified by NIH Stroke Scale score (NIHSS; severe ≥14, less severe <14). The primary efficacy endpoint was the composite of symptomatic or asymptomatic deep-vein thrombosis (DVT), symptomatic pulmonary embolism (PE), or fatal PE during treatment. DVT was confirmed primarily by venography, or ultrasonography when venography was not practical. PE was confirmed by VQ or CT scan, or angiography. Primary safety endpoints included clinically significant intracranial and major extracranial bleeding.
Results: 1762 acute ischemic stroke patients were randomized. Characteristics were similar between groups; mean age was 66.0±12.9 yrs, mean NIHSS score was 11.3. In the efficacy population, enoxaparin (n=666) and UFH (n=669) were given for a mean of 10.5±3.2 days. Enoxaparin resulted in a 43% relative reduction in the risk of the primary efficacy endpoint compared with UFH (10.2% vs 18.1%; RR 0.57; 95% CI 0.44–0.76; p=0.0001, adjusted for NIHSS score). Incidences of VTE events are shown in Table 1. Reductions in the primary endpoint remained significant in patients with a NIHSS score ≥14 (16.3% vs 29.7%, p=0.0036) and <14 (8.3% vs 14.0%, p=0.0043). The composite of clinically significant intracranial and major extracranial bleeding was low and not significantly different between groups (Table 1).
Conclusion: Enoxaparin 40 mg qd is superior to UFH q12h for reducing the risk of VTE in acute ischemic stroke patients, with no significant difference in clinically relevant bleeding. The reduction in VTE risk was consistent in patients with a NIHSS score ≥14 or <14.
Table 1: Incidence of VTE and bleeding Endpoint Enoxaparin n/N (%, 95% CI) UFH n/N (%, 95% CI) *P<0.001 Symptomatic VTE 2/666 (0.3, 0.0–0.7) 6/669 (0.9, 0.2–1.6) Proximal DVT 30/666 (4.5, 2.9–6.1) 64/669 (9.6, 7.3–11.8)* Distal DVT 44/666 (6.6, 4.7–8.5) 85/669 (12.7, 10.2–15.2)* PE 1/666 (0.2, 0.0–0.4) 6/669 (0.9, 0.2–1.6) Composite of major extracranial and clinically significant intracranial bleeding 11/877 (1.3, 0.5–1.9) 6/872 (0.7, 0.1–1.2)
The economic impact of enoxaparin versus unfractionated heparin for prevention of venous thromboembolism in acute ischemic stroke patients