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.


OBJECTIVE
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.
Eriksson
B I
BI
Sahlgrenska University HospitalOstra, Gothenburg, Sweden. b.eriksson@orthop.gu.se
Borris
L
L
Dahl
O E
OE
Haas
S
S
Huisman
M V
MV
Kakkar
A K
AK
Misselwitz
F
F
Kälebo
P
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects* / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D017984:Enoxaparin / Q000008:administration & dosage; D065427:Factor Xa Inhibitors; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage / Q000009:adverse effects; D011183:Postoperative Complications / Q000517:prevention & control; D011655:Pulmonary Embolism / Q000188:drug therapy / Q000517:prevention & control; D000069552:Rivaroxaban; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects; D013923:Thromboembolism / Q000188:drug therapy / Q000517:prevention & control; D020246:Venous Thrombosis / Q000188:drug therapy / Q000401:mortality / Q000517:prevention & control*
D000925:Anticoagulants; D017984:Enoxaparin; D065427:Factor Xa Inhibitors; D009025:Morpholines; D013876:Thiophenes; D000069552:Rivaroxaban