VTE prophylaxis with enoxaparin demonstrated to be superior to unfractionated heparin in acute stroke patients

Enoxaparin is superior to unfractionated heparin (UFH) for prevention of venous thromboembolism (VTE) in acute ischemic stroke patients with partial paralysis, according to David G. Sherman, MD, lead investigator of a trial known as PREVAIL (Prevention of VTE After Acute Ischemic Stroke with LMWH Enoxaparin).

"This is the largest study in stroke patients looking at this issue," Dr Sherman, professor of neurology, University of Texas Health Science Center, San Antonio, told Formulary. "In fact, the study size is almost 3 times that of all of the previous studies that have been done."

Without prophylaxis, approximately 50% of acute stroke patients with paralysis that restricts mobility will develop deep vein thrombosis (DVT) in the leg, and 20% will develop pulmonary embolism (PE), Dr Sherman said.

In the PREVAIL trial, 1,762 patients with acute ischemic stroke (confirmed by computed tomography [CT] or magnetic resonance imaging [MRI] scans) who were unable to walk unassisted due to motor impairment of the leg were randomized within 48 hours of the onset of stroke symptoms to subcutaneous enoxaparin 40 mg daily, or subcutaneous UFH 5,000 IU twice daily. Treatment continued for 10 ± 4 days.

The mean patient age was 66 years, mean time to treatment was 1.2 days after symptom onset, and mean follow-up was 90 days.

The primary end point was a confirmed VTE, defined as the composite of symptomatic or asymptomatic DVT, symptomatic PE, or total PE during the study treatment phase, as assessed by bilateral contrast venography with or without ultrasonography of the lower extremities for all asymptomatic patients and by appropriate diagnostic procedure in the case of symptomatic DVT/PE.

VTE events occurred in 18.1% of the patients randomized to UFH and 10.5% of those randomized to enoxaparin, representing a 43% relative risk reduction with enoxaparin (P=.001). A proximal DVT occurred in 9.6% of the UFH group versus 4.5% of the enoxaparin group, corresponding to a 53% relative risk reduction (P=.001).

The relative risk reductions with enoxaparin were similar in patients with a National Institutes of Health (NIH) Stroke Scale score of <14 (41% RR reduction; P=.004) or ≥14 (45% RR reduction; P=.004).

"The VTE risk reduction benefit was retained over a therapeutic window extending up to 48 hours after symptom onset," Dr Sherman said. "While we encourage physicians to start treatment as soon as it's reasonable, it suggests that even if you're not able to do that, it still works out to 48 hours."

The frequency of any bleeding was low and not significantly different between enoxaparin and UFH (7.9% vs 8.1%, respectively; P=.832). Clinically important bleeding occurred in 1.3% of enoxaparin-treated patients and 0.7% of UFH-treated patients (P=.228), and the rates of intracerebral hemorrhage were 0.5% with both enoxaparin and UFH (P=.520).

The results were consistent across subgroup studies (ie, age, presence or absence of diabetes, race, and body mass index).

The number needed to treat with enoxaparin (instead of UFH) to prevent 1 VTE was 13, and the number needed to harm was 435.

"I would predict that the guidelines writers would see the study as scientifically powerful enough to recommend enoxaparin over UFH," Dr Sherman said. "We're doing a cost analysis but don't yet have the results. Certainly enoxaparin is easier to give; it requires less nursing, it's more predictable, and you don't have to worry about heparin-induced thrombocytopenia, so there's some cost savings there. We'll know more in a precise, scientific way once we get the analysis done."