Goal

- Decrease DVT thrombosis in patients with acute ischemic stroke

Recommendation
- Recommend enoxaparin 40 mg SQ daily versus heparin 5000 units SQ bid or tid given
benefit/risk profile. Recommend enoxaparin over heparin if feasible.
- Consider starting LMWH or UFH for DVT prophylaxis the next day after a stroke and within 48
hours if the benefits outweigh the risks
- It may be considered to to prefer heparin 5000 units SQ bid vs tid given the presumed risk/
benefit ratio

Key points (Prevail trial)

- PE is responsible for 10% of deaths in stroke when no DVT prophylaxis is given
- In patients with hemiplegia, the risk of DVT is 75% and the risk of PE is 20% without DVT px
with fatalities in 1-2%
- PE is found in <1% of strokes after heparin is administered
- DVT is found in <1% of strokes after heparin is administered
- Enoxaparin vs heparin NNT 13 and NNH 173
- Risk of symptomatic intracranial hemorrhage while on DVT prophylaxis is around 1%
- Risk of major extracranial bleed is around 1%
- Heparin 5000 units TID may trend towards increased bleeds versus 5000 units BID without
any increase in benefits

Patient discussion
- We plan to start blood thinner shots to prevent clots. Clots can go to the lung and cause
death. It is recommended by the American Heart Association guidelines to start it after a stroke
given the significant risk of clots if not started. The risk of bleeding is small, but if you have any
signs of bleeding such as a sudden or worsening headache, you should let us know right away.
Prevail trial
The prevail trial involved 1762 patients from 2003-2006. Enoxaparin 40 mg SQ daily
was compared to heparin 5000 units SQ Q12. Initiation of enoxaparin occurred after 1.2 days.
There was no difference for symptomatic DVT (2-4/1000). Risk of pulmonary embolism was
lower for enoxaparin, but not significant (<1%). Major extracranial hemorrhage occurred in 7
people taking enoxaparin and in 0 people taking heparin. 2 of those bleeds resulted in death. 5
patients required transfusion > 2 units of blood. Deaths of patients with clinically important
hemorrhage was 5 in the enoxaparin group and 4 in the heparin group, which was not
statistically significant. The difference between the composite of symptomatic intracranial and
major extracranial hemorrhage was small (11 in the enoxaparin group and 6 in the heparin
group). Enoxaparin reduced the risk of venous thromboembolism by 43% compared with
heparin. In the enoxaparin arm, 10% developed deep vein thrombosis compared with 18% in
the heparin arm. NNT 13 versus NNT 173 when comparing enoxapiarin to heparin. For an
NIHSS score of 14 or more, 16% of patients in the enoxaparin arm developed deep vein
thrombosis compared to 18% in the heparin arm. NNT was 7. Symptomatic intracranial
hemorrhage was similar at around 1%.
Disadvantages of the study were several. The study was not blinded. Trial protocol was
influenced by Sanofi, which also reviewed the data. Sanofi sells enoxaparin.
It was mentioned in this study that heparin 5000 units 3x/day has previously been
compared to 5000 units bid. A meta-analysis showed effectiveness of both drugs with relative
risk reduction of 60% for bid and 72% for tid. However, heparin units 3x/day might have a less
favorable safety profile. There was a trend for more hemorrhagic transformation in Hillborn
study with tid dosing.
Prevail trial notes
- 1762 patients
- 2003-2006
- Enoxaparin 40 mg sq daily versus heparin 5000 units sq q12
- stroke to initiation of enoxaparin around 1.2 days
- No difference for symptomatic DVT 2-4/1000
- Risk of PE lower for enoxaparin but not significant < 1%
- Major extracranial hemorrhage 7 in lovenox vs 0 in heparin. 2 resulting in death. 5 required
transfusion > 2 units of blood. Deaths of patient with clinically important hemorrhage 5 vs 4.
Not clinicaly significant
- frequency of composite symptomatic intracranial and major extracranial hemorrhage small
(11 vs 6)
- lovenox reduced risk of venous thromboembolism by 43% compared with unfractionated
heparin
- enoxaparin versus heparin 10% vs 18% developed DVT
- For enoxaparin versus heparin NNT 13 NNH 173
- for NIHSS score of 14 or more 16 vs 30% or NNT of 7
- symptomatic intracranial hemorrhage similar at around 1%
- trial protocol influenced by Sanofi, which also reviewed the data
- not blinded
- heparin 5000 units 3x/day vs 5000 units bid
- for heparin 3x/day vs bid, meta-analysis showed effectiveness of both drug regimens
compared to placebo
- RR 60% for bid; 72% for tid
- heparin 5000 tid might have a less favorable safety profile
- trend for more hemorrhagic transformation in Hillborn study with tid dosing

Hillborn study. Lovenox vs heparin for prevention of DVT in acute ischemic stroke.
- lovenox 40 mg vs heparin 5000 sq tid
- 212 patients; efficacy analysis (n=148)
- patients given lovenox vs heparin (20% vs 35% for primary endpoint of dvt) 95% CI 0.8-29.2 p
= 0.044
- duration of prophylaxis 6-14 days