PREVAIL: VTE Reduced With Enoxaparin vs Heparin in Stroke

Susan Jeffrey

December 14, 2006

December 14, 2006 (Orlando) — Results of a randomized trial show a significant reduction in venous-thromboembolism (VTE) events in stroke patients receiving the low-molecular-weight (LMW) heparin enoxaparin ( Lovenox, Sanofi-Aventis) vs unfractionated heparin, without a significant increase in clinically important bleeding.

The results, from the Prevention of VTE after Acute Ischemic Stroke with LMWH Enoxaparin (PREVAIL) study, were presented here at American Society of Hematology (ASH) 48th Annual Meeting and Exposition. PREVAIL was funded by Sanofi-Aventis.

David G. Sherman, MD, from the University of Texas Health Science Center, in San Antonio, was principal investigator of the trial, which included patients from 15 countries.

"We conclude that, in these paralyzed stroke patients at high risk for [deep venous thrombosis] DVT and the worst possible side effect of [pulmonary embolism] PE, enoxaparin is significantly more effective in preventing them from developing a DVT or PE than was unfractionated heparin," Dr. Sherman told Medscape.

At-Risk Patients

Patients with acute ischemic stroke are at increased risk for VTE events, including DVT and PE. "The risk if untreated is about 50% — about half of the patients will develop this," Dr. Sherman noted. Prophylaxis with either LMW heparin or unfractionated heparin is currently recommended in these patients. Studies to date comparing the 2 agents, however, are limited in methodology and sample size, the authors write.

PREVAIL was an open-label trial comparing the efficacy and safety of enoxaparin vs unfractionated heparin in preventing VTE events in patients with acute ischemic stroke confirmed by CT who had sufficient paralysis that they were unable to walk unassisted.

A total of 1762 patients were enrolled within 48 hours of stroke-symptom onset and randomized to receive either 40 mg daily of enoxaparin given subcutaneously or 5000 IU of heparin twice daily, for 10 days, plus or minus 4 days — depending on when the patient was able to become ambulatory. They were followed for a period of 90 days. Patients were also stratified by stroke severity according to National Institutes of Health Stroke Scale (NIHSS) scores as severe (14 or greater) and less severe (less than 14).

The primary efficacy end point was a composite of symptomatic or asymptomatic DVT and symptomatic or fatal PE during the treatment period. Safety end points included symptomatic intracranial bleeding, major extracranial bleeding, and all-cause mortality. To be included in the primary efficacy analysis, all patients must have undergone a venogram or other imaging; of the 1762 patients enrolled, 1335 were considered in the primary efficacy end point, 666 in the enoxaparin group and 669 in the unfractionated heparin group.

Results showed a 43% reduction in the primary end point (RR, 0.57; 95% CI, 0.44 -0.76; P = .0001 adjusted for NIHSS score) with enoxaparin vs unfractionated heparin.

PREVAIL: Primary Composite End Point and VTE Events

End point
Enoxaparin, n (%)
Unfractionated heparin, n (%)
P
Composite end point
77 (10.2)
161 (18.1)
.0001
Symptomatic VTE
2 (0.3)
6 (0.9)
.096
Proximal DVT
30 (4.5)
64 (9.6)
< .001
Distal DVT
44 (6.6)
85 (12.7)
< .001
PE
1 (0.2)
6 (0.9)
.059

The reduction in the primary end point remained significant in those with both more and less severe strokes.

PREVAIL: Primary End-Point Results in Patients With More and Less Severe Strokes
NIHSS score
Enoxaparin (%)
UFH (%)
P
> 14
16.3
29.7
.0036
< 14
8.3
14.0
.0043

In terms of safety, the composite of major extracranial and clinically significant intracranial bleeding was low and not significantly different between the groups, the authors note.

PREVAIL: Major Extracranial and Clinically Significant Intracranial Bleeding
End point
Enoxaparin, n (%)
UFH, n (%)
P
Composite of major extracranial and clinically significant intracranial bleeding
11 (1.3)
6 (0.7)
.2

In the past, treating physicians have had to make a choice at the beside, typically between heparin and an LMW heparin — enoxaparin being the most commonly used LMW heparin in the United States, Dr. Sherman said.

"Now with the PREVAIL study, we have evidence from a single large study that shows in a very powerful way that enoxaparin is more effective in preventing clots than is unfractionated heparin. My suspicion is that many treating physicians, if not most or all, will select enoxaparin as their drug of choice for prevention of DVT and PE as opposed to unfractionated heparin."


The PREVAIL study was funded by Sanofi-Aventis, maker of enoxaparin. Dr. Sherman is on the Sanofi-Aventis speaking bureau and consulted with Sanofi-Aventis on stroke-related research and educational activities.

ASH 48th Annual Meeting and Exposition: Abstract 713.

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