Oral, direct Factor Xa inhibition with BAY 59-7939 for the prevention of venous thromboembolism after total hip replacement

• BACKGROUND: Joint replacement surgery is an appropriate model for dose-ranging studies investigating new anticoagulants. OBJECTIVES: To assess the efficacy and safety of a novel, oral, direct factor Xa (FXa) inhibitor--BAY 59-7939--relative to enoxaparin in patients undergoing elective total hip replacement. METHODS: In this double-blind, double-dummy, dose-ranging study, patients were randomized to oral BAY 59-7939 (2.5, 5, 10, 20, or 30 mg b.i.d.), starting 6-8 h after surgery, or s.c. enoxaparin 40 mg once daily, starting on the evening before surgery. Treatment was continued until mandatory bilateral venography was performed 5-9 days after surgery. RESULTS: Of 706 patients treated, 548 were eligible for the primary efficacy analysis. The primary efficacy endpoint was the incidence of any deep vein thrombosis, non-fatal pulmonary embolism, and all-cause mortality; rates were 15%, 14%, 12%, 18%, and 7% for BAY 59-7939 2.5, 5, 10, 20, and 30 mg b.i.d., respectively, compared with 17% for enoxaparin. The primary efficacy analysis did not demonstrate any significant trend in dose-response relationship for BAY 59-7939. The primary safety endpoint was major, postoperative bleeding; there was a significant increase in the frequency of events with increasing doses of BAY 59-7939 (P = 0.045), but no significant differences between individual BAY 59-7939 doses and enoxaparin. CONCLUSIONS: When efficacy and safety were considered together, the oral, direct FXa inhibitor BAY 59-7939, at 2.5-10 mg b.i.d., compared favorably with enoxaparin for the prevention of venous thromboembolism in patients undergoing elective total hip replacement.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kirurgi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Surgery (hsv//eng)

Nyckelord

Adult

Aged

Aged

80 and over

Anticoagulants/*administration & dosage/adverse effects

Arthroplasty

Replacement

Hip/*adverse effects/methods

Dose-Response Relationship

Drug

Double-Blind Method

Enoxaparin/administration & dosage

Factor Xa/*antagonists & inhibitors

Female

Hemorrhage/chemically induced

Humans

Male

Middle Aged

Morpholines/administration & dosage/adverse effects

Postoperative Complications/prevention & control

Pulmonary Embolism/drug therapy/prevention & control

Thiophenes/administration & dosage/adverse effects

Thromboembolism/drug therapy/prevention & control

Venous Thrombosis/drug therapy/mortality/*prevention & control

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)