The efficacy and safety of enoxaparin versus unfractionated heparin for the prevention of venous thromboembolism after acute ischaemic stroke (PREVAIL Study): an open-label randomised comparison.
BACKGROUND
Venous thromboembolism prophylaxis with low molecular weight heparin or unfractionated heparin is recommended in acute ischaemic stroke, but which regimen provides optimum treatment is uncertain. We aimed to compare the efficacy and safety of enoxaparin with that of unfractionated heparin for patients with stroke.


METHODS
1762 patients with acute ischaemic stroke who were unable to walk unassisted were randomly assigned within 48 h of symptoms to receive either enoxaparin 40 mg subcutaneously once daily or unfractionated heparin 5000 U subcutaneously every 12 h for 10 days (range 6-14). Patients were stratified by National Institutes of Health Stroke Scale (NIHSS) score (severe stroke > or =14, less severe stroke <14). The primary efficacy endpoint was the composite of symptomatic or asymptomatic deep vein thrombosis, symptomatic pulmonary embolism, or fatal pulmonary embolism. Primary safety endpoints were symptomatic intracranial haemorrhage, major extracranial haemorrhage, and all-cause mortality. This study is registered with ClinicalTrials.gov, number NCT00077805.


RESULTS
In the efficacy population (ie, one or more dose received, presence of deep vein thrombosis or pulmonary embolism, or assessment for venous thromboembolism), enoxaparin (n=666) and unfractionated heparin (669) were given for 10.5 days (SD 3.2). Enoxaparin reduced the risk of venous thromboembolism by 43% compared with unfractionated heparin (68 [10%] vs 121 [18%]; relative risk 0.57, 95% CI 0.44-0.76, p=0.0001; difference -7.9%, -11.6 to -4.2); this reduction was consistent for patients with an NIHSS score of 14 or more (26 [16%] vs 52 [30%]; p=0.0036) or less than 14 (42 [8%] vs 69 [14%]; p=0.0044). The occurrence of any bleeding was similar with enoxaparin (69 [8%]) or unfractionated heparin (71 [8%]; p=0.83). The frequency of the composite of symptomatic intracranial and major extracranial haemorrhage was small and closely similar between groups (enoxaparin 11 [1%] vs unfractionated heparin 6 [1%]; p=0.23). We noted no difference for symptomatic intracranial haemorrhage between groups (4 [1%] vs 6 [1%], respectively; p=0.55); the rate of major extracranial bleeding was higher with enoxaparin than with unfractionated heparin (7 [1%] vs 0; p=0.015).


CONCLUSIONS
Our results suggest that for patients with acute ischaemic stroke, enoxaparin is preferable to unfractionated heparin for venous thromboembolism prophylaxis in view of its better clinical benefits to risk ratio and convenience of once daily administration.
Sherman
David G
DG
Department of Medicine (Neurology), University of Texas Health Science Center, San Antonio, TX, USA. Electronic address: sherman@uthscsa.edu.
Albers
Gregory W
GW
Department of Neurology and Neurological Sciences, Stanford University Medical Center, Palo Alto, CA, USA.
Bladin
Christopher
C
Box Hill Hospital (Monash University), Melbourne, Australia.
Fieschi
Cesare
C
University "La Sapienza", Rome, Italy.
Gabbai
Alberto A
AA
UNIFESP-Disciplina de Neurologia, Sao Paulo, Brazil.
Kase
Carlos S
CS
Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
O'Riordan
William
W
Paradise Valley Hospital, National City, CA, USA.
Pineo
Graham F
GF
University of Calgary, Calgary, Alberta, Canada.
D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use*; D017984:Enoxaparin / Q000627:therapeutic use*; D005260:Female; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D006801:Humans; D002546:Ischemic Attack, Transient / Q000145:classification / Q000150:complications*; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D012307:Risk Factors; D012720:Severity of Illness Index; D020246:Venous Thrombosis / Q000209:etiology* / Q000517:prevention & control*
D000925:Anticoagulants; D017984:Enoxaparin; D006495:Heparin, Low-Molecular-Weight