Enoxaparin Superior to Unfractionated Heparin for Preventing Deep Vein Clots in Stroke Patients
SAN FRANCISCO—Low-molecular-weight heparin, enoxaparin (Lovenox), is superior to unfractionated heparin for venous thromboembolism (VTE) prophylaxis in paralyzed acute ischemic stroke patients, according to a large prospective, randomized, open-label study sponsored by Sanofi-Aventis.
Treatment with enoxaparin resulted in a statistically significant 43 percent reduction in venous thromboembolic events compared with unfractionated heparin, with no significant difference in clinically important hemorrhage, reported David G. Sherman, MD, professor of medicine in the division of neurology at the University of Texas Health Science Center in San Antonio. Patients benefited even when the treatment was not started for 24 to 48 hours after the onset of ischemic stroke symptoms, he said in his late-breaking oral presentation here at the American Stroke Association International Stroke Conference last month.
Dr. Sherman noted that if paralyzed stroke patients receive no VTE prophylaxis, clots occur in about 50 percent of the cases.
Guidelines say all these patients need some prophylaxis but they do not spell out what drug should be used, he said, primarily because studies are not large enough for definite recommendations.
”These results suggest that enoxaparin could become the preferred treatment to prevent deep vein clots in stroke patients,” Dr. Sherman added.
The Prevention of Venous Thromboembolism after Acute Ischemic Stroke with LMWH Enoxaparin (PREVAIL) Trial included 1,762 patients with an acute ischemic stroke — confirmed by CT or MRI — who could not walk without assistance due to weakness or clumsiness of the leg.
Within 48 hours of symptom onset, 878 patients were randomized to treatment with 5,000 IU of subcutaneous unfractionated heparin twice a day. The other 884 patients were assigned to receive 40 mg of subcutaneous enoxaparin once daily. Both drugs were given for an average of 10 days.
The primary efficacy endpoint was VTE, a composite of symptomatic or asymptomatic deep-vein thrombosis (DVT), symptomatic pulmonary embolism, or fatal pulmonary embolism during treatment.
Deep-vein thrombosis was confirmed by venography, or ultrasonography if venography was not practical. Pulmonary embolism was confirmed by ventilation-perfusion or CT scan, or angiography.
The results showed that, by 90 days, 18.1 percent of patients in the unfractionated heparin group had VTEs versus 10.2 percent of those in the enoxaparin arm.
Intracranial bleeding, the main concern with these agents, occurred in 0.7 percent of patients given unfractionated heparin and 1.3 percent of patients given enoxaparin, not a significant difference.
“The number needed to treat to avoid one VTE event with enoxaparin is 13,” Dr. Sherman said. “The number needed to treat to harm, leading to a clinically important bleeding event, is 435.”
Further analysis showed that the significant reduction in VTE risk with enoxaparin versus unfractionated heparin was maintained whether the treatment started within 24 hours of symptom onset or 24 to 48 hours after onset.
Among the 36 percent of participants who received enoxaparin within 24 hours, 8.1 percent had VTE events; among those receiving unfractionated heparin in this time frame, the figure was 18.5 percent. This translates to a significant 56 percent reduction in risk, Dr. Sherman said.
Among the 64 percent of patients who received treatment 24 to 48 hours after symptom onset, 11.3 percent of those given enoxaparin and 17.8 percent those given unfractionated heparin suffered VTE, a significant 36 percent reduction in risk.
When patients were stratified by entry National Institute of Health Stroke Scale Scores, treatment with enoxaparin again resulted in significant reduction in VTE risk both among those with scores of less than 14 points and those with scores of 14 or more points. (Scores higher than 23 on the scale indicate severe neurologic disabilities.)
Dr. Sherman also noted that enoxaparin resulted in a consistent 53 percent reduction in proximal DVT, compared with unfractionated heparin.
Additionally, the clinical benefit of enoxaparin on VTE prevention did not affect outcomes at three months compared to unfractionated heparin, he said. By 90-day follow-up, 5.3 percent of patients taking unfractionated heparin had progressed versus 5.0 percent of those on enoxaparin. Strokes recurred in 1.5 percent of patients given unfractionated heparin versus 1.7 percent of those given enoxaparin. Neither difference was significant.
“Now physicians caring for stroke patients who are paralyzed have some guidance about what treatment to choose. Enoxaparin should become the standard of care,” Dr. Sherman said.
But Philip B. Gorelick, MD, the John S. Garvin Professor and head of the department of neurology and rehabilitation at the University of Illinois at Chicago, said it's too soon to make that conclusion.
”The efficacy data in this study are positive and solid. But a dramatic cost difference between unfractionated heparin and enoxaparin may limit adoption” of enoxaparin until pharmacoeconomic studies are available, said Dr. Gorelick.
Dr. Sherman said the PREVAIL researchers are now conducting such a study. The results, he expects, will show that treatment with enoxaparin is cost-effective, when they are presented at a future medical meeting.
ARTICLE IN BRIEF
✓ Treatment with enoxaparin resulted in a statistically significant 43 percent reduction in venous thromboembolic events compared with unfractionated heparin, with no significant difference in clinically important hemorrhage.