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A Double-blind, Randomized Comparison

Russell D. Hull, MBBS, MSc; Graham F. Pineo, MD; Charles Francis, MD; David Bergqvist, MD, PhD; Carin Fellenius, CCRN, RNA; Karin Soderberg, CLT; Anna Holmqvist, BSc; Michael Mant, MB, ChB; Richard Dear, MBBS; Barry Baylis, MD; Andrew Mah, BSc; Rollin Brant, PhD; for the North American Fragmin Trial Investigators

Arch Intern Med. 2000;160:2208-2215.

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.

From the Thrombosis Research Unit, University of Calgary, Calgary, Alberta (Drs Hull, Pineo, and Brant and Mr Mah); University of Rochester Medical Center, Rochester, NY (Dr Francis); Uppsala University, Uppsala (Dr Bergqvist), Pharmacia & Upjohn, Stockholm (Mss Fellenius, Soderberg, and Holmqvist), Sweden; University of Alberta Hospital, Edmonton (Dr Mant); Peter Lougheed Center and Calgary General Hospital, Calgary (Dr Dear); and Foothills Medical Center, Calgary (Dr Baylis).

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Low-Molecular-Weight Heparin Prophylaxis Using Dalteparin in Close Proximity to Surgery vs Warfarin in Hip Arthroplasty Patients: A Double-blind, Randomized Comparison
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Arch Intern Med. 2000;160(14):2199-2207.
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