ASA: Lovenox Bests Unfractionated Heparin Versus Post-Stroke Thrombosis

February 12, 2007

SAN FRANCISCO -- The low-molecular-weight heparin Lovenox (enoxoparin) reduces the post-stroke relative risk of venous thrombosis by 43% compared with unfractionated heparin, researchers said here.

SAN FRANCISCO, Feb. 12 -- The low molecular weight heparin Lovenox (enoxoparin) reduces the relative risk of venous thrombosis after a stroke by 43% compared with unfractionated heparin, researchers said here.

The benefit was seen even if the drug was not started until the second day after a stroke and was not associated excess bleeding complications, according to David G. Sherman, M.D., of the University of Texas Health Science Center in San Antonio.

The findings suggest that unfractionated heparin should be off the table for prophylaxis in acute ischemic stroke patients, Dr. Sherman reported at the American Stroke Association meeting.

"This is a long awaited direct comparison," he added. "I believe that it will assume the role of the preferred prophylactic anticoagulant."

However, cost cannot be overlooked, commented Philip Gorelick, M.D., M.P.H., of the University of Illinois at Chicago, who moderated a press conference in which the study was discussed.

"On a patient-by-patient case you are going to want it," he said referring to Lovenox. "That's not always the choice though."

As reported in August, drug costs for a six-day course of Lovenox for a 176- pound patient would be compared to just for unfractionated heparin.

The prospective open-label study included 1,762 patients with acute ischemic stroke confirmed by CT or MRI brain imaging. Participants were randomized to 40 mg of subcutaneous Lovenox once daily or 5,000 units of subcutaneous unfractionated heparin twice daily.

Over three months of follow-up, the findings for Lovenox versus unfractionated heparin were:

  • A significant reduction in the relative risk of venous thromboembolic events (10.2% versus 18.1%, P=0.0001), and
  • No difference in the rate of clinically important bleeding events (1.3% versus 0.7%).

The reduction in risk of proximal deep vein thrombosis was even greater at 53% for Lovenox over unfractionated heparin (4.5% versus 9.6%, P=0.0003). However, the difference in symptomatic venous thrombosis was not significant (P=0.096).

The number needed to treat to avoid one venous thrombosis was 13. The number-needed-to-treat to lead to a clinically important bleeding event was 435.

The researchers reported that the benefit was greater if patients were treated staring sooner than 24 hours after stroke (relative risk 0.44, 95% confidence interval 0.26 to 0.72, P=0.0008). However, the improvement over unfractionated heparin was still significant when treatment was initiated from 24 hours to 48 hours (RR 0.64, 95% CI 0.46 to 0.89, P=0.0074).

The benefit also remained significant regardless of stroke severity.

For secondary neurological endpoints, the findings were:

  • Stroke progression was no different between groups (5.3% unfractionated versus 5.0% Lovenox),
  • Stroke recurrence was similar between groups (1.5% unfractionated versus 1.7% Lovenox), and
  • Modified Rankin Scale scores greater than 2 points (5.3% unfractionated versus 5.0% Lovenox).