Low-molecular-weight heparin prophylaxis using dalteparin extended out-of-hospital vs in-hospital warfarin/out-of-hospital placebo in hip arthroplasty patients: a double-blind, randomized comparison. North American Fragmin Trial Investigators.
BACKGROUND
No randomized trials have directly evaluated the need for extended out-of-hospital thromboprophylaxis for patients who have hip arthroplasty in the United States or Canada. The uncertainty as to the need for extended prophylaxis in North American patients is complicated by early hospital discharge, resulting in a short thromboprophylaxis interval.


METHODS
To resolve this uncertainty, we performed a randomized double-blind trial in 569 patients who underwent hip arthroplasty comparing the use of dalteparin sodium started immediately before surgery or early after surgery and extended out-of-hospital to an overall interval of 35 days with the use of warfarin sodium in-hospital and placebo out-of-hospital.


RESULTS
For patients with interpretable venograms in the preoperative, postoperative, and combined dalteparin groups, new proximal vein thrombosis out-of-hospital was observed in 1.3%, 0. 7% (P =.04), and 1.0% (P =.02) of patients, respectively, compared with 4.8% in the in-hospital warfarin/out-of-hospital placebo group. The respective overall cumulative frequencies of all deep vein thrombosis were 30 (17.2%) of 174 patients (P<.001), 38 (22.2%) of 171 (P =.003), and 68 (19.7%) of 345 (P<.001) in the dalteparin groups compared with 69 (36.7%) of 188 for the in-hospital warfarin/out-of-hospital placebo group. For proximal deep vein thrombosis, the respective frequencies were 5 (3.1%) of 162 (P =.02), 3 (2.0%) of 151 (P =.007), and 8 (2.6%) of 313 (P =.002) compared with 14 (9.2%) of 153. No major bleeding occurred during the extended prophylaxis interval.


CONCLUSIONS
Extended dalteparin prophylaxis resulted in significantly lower frequencies of deep vein thrombosis compared with in-hospital warfarin therapy. Despite in-hospital thromboprophylaxis, patients having hip arthroplasty in the United States and Canada remain at moderate risk out-of-hospital. The number needed to treat provides a public health focus; only 24 to 28 patients require extended prophylaxis to prevent 1 new out-of-hospital proximal vein thrombosis. Recent studies demonstrate that asymptomatic deep vein thrombi cause the postphlebitic syndrome; thus, extended out-of-hospital prophylaxis will lessen the burden to both the patient and society.
Hull
R D
RD
Thrombosis Research Unit, 601 South Tower, Foothills Hospital, 1403-29 Street NW, Calgary, Alberta, Canada T2N 2T9.
Pineo
G F
GF
Francis
C
C
Bergqvist
D
D
Fellenius
C
C
Soderberg
K
K
Holmqvist
A
A
Mant
M
M
Dear
R
R
Baylis
B
B
Mah
A
A
Brant
R
R
D000925:Anticoagulants / Q000008:administration & dosage*; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects*; D002170:Canada / Q000453:epidemiology; D017985:Dalteparin / Q000008:administration & dosage*; D004311:Double-Blind Method; D006801:Humans; D015994:Incidence; D007279:Injections, Subcutaneous; D007297:Inpatients; D008875:Middle Aged; D010045:Outpatients; D010690:Phlebography; D011182:Postoperative Care; D011300:Preoperative Care; D014481:United States / Q000453:epidemiology; D020246:Venous Thrombosis / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D014859:Warfarin / Q000008:administration & dosage*
D000925:Anticoagulants; D014859:Warfarin; D017985:Dalteparin