SAN FRANCISCO — Enoxaparin, a low-molecular-weight heparin, gave acute ischemic stroke patients significantly better protection against venous thromboembolism, compared with unfractionated heparin, in a large, open-label trial presented at the 32nd International Stroke Conference.
Venous thromboembolic (VTE) events occurred in 10.2% of 884 patients on enoxaparin prophylaxis, compared with 18.1% of 878 patients on unfractionated heparin, Dr. David G. Sherman reported. Enoxaparin reduced the relative risk of VTE by 43% in the trial, which randomized 1,762 patients who could not walk unassisted within 48 hours of acute ischemic stroke.
All subgroups benefited, including patients with more severe strokes and those who started prophylaxis more than 24 hours after their strokes, according to Dr. Sherman, a professor of medicine and chief of the division of neurology at the University of Texas Health Science Center in San Antonio. Compared with unfractionated heparin, enoxaparin reduced proximal deep vein thrombosis by 53%.
Sanofi-Aventis, which markets enoxaparin as the antithrombotic Lovenox, sponsored the Prevention of VTE After Acute Ischemic Stroke with Low-Molecular-Weight-Heparin Enoxaparin (PREVAIL) trial. Dr. Sherman is a consultant to and is on the speakers' bureau of the company.
Still to come is a thorough pharmacoeconomic analysis of enoxaparin prophylaxis. At a press briefing prior to the presentation, Dr. Sherman said the promised analysis would include indirect costs such as length of hospital stay as well as the price of the therapy.
Up to now, various stroke-care guidelines have called for VTE prophylaxis without specifying an agent or dose in the absence of large trials comparing agents, according to Dr. Sherman. PREVAIL gives physicians caring for paralyzed stroke patients “some guidance to direct them in making a decision on which anticoagulants to use,” he said.
The trial “suggests that enoxaparin 40 mg once daily for up to 14 days could become the preferred treatment for VTE prophylaxis in acute ischemic stroke patients,” he said in the conclusion of his presentation. He declined, however, to predict how standards-setting groups would react to PREVAIL.
The cost analysis could prove critical to how standards-setting groups view enoxaparin, according to Dr. Philip Gorelick, moderator of the press briefing. Despite its superiority in PREVAIL, he said in an interview that enoxaparin is an expensive drug that must compete with other stroke treatments as well as unfractionated heparin for health care dollars. “We have to see these data, because cost is very important,” said Dr. Gorelick, John S. Garvin professor and head of the department of neurology and rehabilitation at Rush Medical College, Chicago. “The absolute numbers of people that could be affected by the results of this trial are huge,” he added.
Patients in the study received either 40 mg of enoxaparin subcutaneously once a day or 5,000 IU of unfractionated heparin twice a day. Efficacy was based on whether patients had symptomatic or asymptomatic deep-vein thrombosis, symptomatic pulmonary embolism, or a fatal pulmonary embolism during 6–14 days of treatment. Both legs of asymptomatic patients were screened by venography.
Nearly two-thirds of patients in the trial started prophylaxis 24–48 hours after their strokes, but they had as much benefit as those who started sooner. “Even if we were not able to start in the first 24 hours, the treatment was effective,” Dr. Sherman said.
Adverse events were similar in both arms of PREVAIL. Dr. Sherman reported that clinically significant bleeds occurred in 1.3% of patients on enoxaparin and 0.7% of those given unfractionated heparin. Treating 13 patients with enoxaparin could prevent one VTE, he said; treating 435 patients could lead to one important clinical bleeding event.
At the end of 90 days' follow-up, investigators found no significant differences in neurologic end points, he said. Stroke progression and modified Rankin Scale scores of less than 2 were seen, respectively, in about 5% of both groups. Strokes recurred in fewer than 2% of patients regardless of prophylaxis.