ORLANDO -- In patients with acute ischemic stroke, Lovenox (enoxaparin) was superior to unfractionated heparin every 12 hours for reducing the risk of venous thromboembolism, reported investigators from the PREVAIL trial.
ORLANDO, Dec. 15 -- In patients with acute ischemic stroke, daily Lovenox (enoxaparin) was superior to unfractionated heparin every 12 hours for reducing the risk of venous thromboembolism (VTE), reported investigators from the PREVAIL trial.
There were no significant differences in clinically relevant bleeding between patients treated with Lovenox, a low-molecular weight heparin, and those who received unfractionated heparin, reported David G. Sherman, M.D., professor of neurology at the University of Texas Health Science Center at San Antonio.
Dr. Sherman reported the results of the study, funded by Sanofi-Aventis, the maker of Lovenox, at the American Society of Hematology meeting here.
The PREVAIL (Prevention of VTE after Acute Ischemic Stoker with LMWH Enoxaparin) study was designed to see whether Lovenox was better than unfractionated heparin for VTE prophylaxis in acute ischemic stroke patients, and to evaluate efficacy and safety of the drugs according to stroke severity.
A total of 1,762 patients from 15 countries were enrolled in the study. Eligible patients had acute ischemic strokes confirmed by CT scan, and were unable to walk unassisted because of motor impairment of the leg. The mean patient age was 66.0 12.9 years, mean NIH Stroke Scale score (NIHSS) was 11.3.
The trial design was prospective, open-label, parallel group. Patients were randomly assigned within 48 hours of the onset of stroke symptoms to receive Lovenox at 40 mg once daily via subcutaneous injection, or unfractionated heparin 5,000 IU every 12 hours, also subcutaneously. The drugs were delivered for 10 four days.
Patients were stratified by NIH Stroke Scale score (NIHSS) as having either severe stroke (NIHSS score ?14) or less severe (< 14).
The primary efficacy endpoint was a composite of symptomatic or asymptomatic deep-vein thrombosis (DVT), symptomatic pulmonary embolism, or fatal during treatment.
The investigators confirmed the presence of DVT primarily by venography, or by ultrasonography when venography was not practical.
Pulmonary embolism was confirmed by ventilation quantification or CT scan, or angiography.
The primary safety endpoints included clinically significant intracranial and major extracranial bleeding.
The efficacy analysis included data on 666 patients who received Lovenox, and 669 who received unfractionated heparin. The drugs were given for a mean of 10.5 3.2 days.
The composite endpoint, adjusted for NIHSS score, occurred in 10.2% of patients on Lovenox compared with 18.1% of patients on unfractionated heparin, translating into a relative risk reduction of 43% (relative risk 0.57, 95% confidence interval, 0.44-0.76; P=0.0001).
Lovenox was also associated with significantly fewer events in patients with severe stroke, 16.3% compared with 29.7% for unfractionated heparin (P=0.0036) and in patients with less-severe stroke (8.3% versus 14.0%, respectively, P=0.0043).
The composite of clinically significant intracranial and major extracranial bleeding was low and was not significantly different between the groups, at 1.3% for Lovenox and 0.7% for unfractionated heparin (P=0.20).
"Balancing the benefits of lowering the risk of venous thromboembolism, while minimizing the risk of bleeding, is a very important element in choosing prophylactic regimens for this particularly fragile patient population, as it combines the usual factors of venous thromboembolism in addition to the stroke context," Dr. Sherman said.