What is the efficacy of Lovenox (enoxaparin) 1.5 mg/kg once daily versus 1 mg/kg twice daily for outpatient treatment of stroke?

From the Guidelines

For outpatient treatment of stroke with enoxaparin (Lovenox), the 1 mg/kg twice daily dosing regimen is generally preferred over the 1.5 mg/kg once daily regimen. This preference is based on the need for consistent anticoagulation levels throughout the 24-hour period to prevent both recurrent thrombotic events and hemorrhagic transformation in stroke patients. The twice daily dosing regimen provides a more stable anticoagulation profile, which is crucial in the management of stroke patients.

Key Considerations

• The 1 mg/kg twice daily regimen has been more extensively studied specifically for stroke treatment and has demonstrated better outcomes in terms of preventing recurrent strokes while maintaining an acceptable bleeding risk profile 1.
• The once daily 1.5 mg/kg dosing creates higher peak levels and lower trough levels, potentially increasing bleeding risk at peak and reduced protection at trough.
• For implementation, patients should be taught proper subcutaneous injection technique, instructed to administer doses approximately 12 hours apart, and monitored regularly for signs of bleeding or recurrent stroke symptoms.
• Renal function should be assessed before starting therapy, as dose adjustments are needed for patients with creatinine clearance below 30 mL/min, as indicated by guidelines for the management of patients with acute ischemic stroke 1.
• Anti-Xa monitoring is not routinely required but may be considered in patients with obesity, renal impairment, or pregnancy, reflecting the need for personalized care in these populations.

Evidence Base

The preference for the 1 mg/kg twice daily dosing regimen is supported by the most recent and highest quality evidence available, including guidelines from the American Heart Association/American Stroke Association 1. While earlier studies may have suggested varying efficacy of different dosing regimens, the current consensus, based on more recent and comprehensive data, favors the twice daily regimen for its balance of efficacy and safety in preventing recurrent strokes and managing bleeding risk.

From the Research

Efficacy of Lovenox 1.5 mg/kg Once Daily vs 1 mg/kg Twice Daily

• The study 2 compared the efficacy and safety of an investigational enoxaparin regimen, 1.5 mg/kg once daily, as a bridge to warfarin for the outpatient treatment of acute venous thromboembolism, with enoxaparin 1 mg/kg twice daily.
• The results showed that once daily enoxaparin, 1.5 mg/kg, was as effective with a similar safety profile as twice daily enoxaparin, 1mg/kg, for initial treatment of acute venous thromboembolism in the outpatient setting.
• Another study 3 compared the efficacy and safety of deep-vein thrombosis treatment using once-daily subcutaneous enoxaparin in the outpatient setting with intravenous unfractionated heparin in hospital, and found that once-daily subcutaneous enoxaparin was at least as effective and as well tolerated as in-hospital intravenous unfractionated heparin.

Safety of Lovenox 1.5 mg/kg Once Daily vs 1 mg/kg Twice Daily

• The study 2 found no major bleeding complications in the case group (1.5 mg/kg once daily), compared to 3 (3.8%) in the control group (1 mg/kg twice daily).
• The study 3 found that the incidences of bleeding events and adverse events in the enoxaparin and unfractionated-heparin groups were similar.
• However, the study 4 found that the rate of major bleeding in patients with a creatinine clearance concentration of <30 mL/min was higher with enoxaparin compared to unfractionated heparin.

Outpatient Treatment of Stroke

• The study 5 compared the efficacy and safety of enoxaparin with that of unfractionated heparin for patients with acute ischaemic stroke, and found that enoxaparin reduced the risk of venous thromboembolism by 43% compared with unfractionated heparin.
• The study 6 investigated extended-duration thromboprophylaxis with enoxaparin in ischemic stroke patients, and found that extended-duration prophylaxis reduced venous thromboembolism incidence versus placebo, but was associated with an increase in major bleeding.