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Circulation. 2004;110:1658-1663
Published online before print September 13, 2004, doi: 10.1161/01.CIR.0000142859.77578.C9
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(Circulation. 2004;110:1658-1663.)
© 2004 American Heart Association, Inc.


Vascular Medicine

Single-Arm Study of Bridging Therapy With Low-Molecular-Weight Heparin for Patients at Risk of Arterial Embolism Who Require Temporary Interruption of Warfarin

M.J. Kovacs, MD, FRCPC; C. Kearon, MD, FRCPC; M. Rodger, MD, FRCPC; D.R. Anderson, MD, FRCPC; A.G.G. Turpie, MD, FRCPC; S.M. Bates, MD, FRCPC; L. Desjardins, MD, FRCPC; J. Douketis, MD, FRCPC; S.R. Kahn, MD, FRCPC, SMBD; S. Solymoss, MD, FRCPC; P.S. Wells, MD, FRCPC

From the London Health Sciences Centre, London, Ontario (M.J.K.); Hamilton Health Sciences Centre, Hamilton, Ontario (C.K.); Ottawa Hospital, Ottawa, Ontario (M.R.); Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia (D.R.A.); Hamilton Health Sciences-General Hospital, Hamilton, Ontario (A.G.G.T.); McMaster University Medical Centre, Hamilton, Ontario (S.M.B.); Hospital University Laval, Sainte Foy, Quebec (L.D.); St Joseph’s Health Centre, Hamilton, Ontario (J.D.); Jewish General Hospital, Montreal, Quebec (S.R.K.); St Mary’s Hospital, Montreal, Quebec (S.S.); and Ottawa Hospital, Ottawa, Ontario (P.W.), Canada.

Correspondence to Dr Michael J. Kovacs, London Health Sciences Centre, 800 Commissioners Rd E, London, Ontario, Canada N6A 4G5. E-mail michael.kovacs{at}lhsc.on.ca

Received April 9, 2004; revision received July 7, 2004; accepted July 14, 2004.

Background— When warfarin is interrupted for surgery, low-molecular-weight heparin is often used as bridging therapy. However, this practice has never been evaluated in a large prospective study. This study was designed to assess the efficacy and safety of bridging therapy with low-molecular-weight heparin initiated out of hospital.

Methods and Results— This was a prospective, multicenter, single-arm cohort study of patients at high risk of arterial embolism (prosthetic valves and atrial fibrillation with a major risk factor). Warfarin was held for 5 days preoperatively. Low-molecular-weight heparin was given 3 days preoperatively and at least 4 days postoperatively. Patients were followed up for 3 months for thromboembolism and bleeding. Eleven Canadian tertiary care academic centers participated; 224 patients were enrolled. Eight patients (3.6%; 95% CI, 1.8 to 6.9) had an episode of thromboembolism, of which 2 (0.9%; 95% CI, 0.2 to 3.2) were judged to be due to cardioembolism. Of these 8 episodes of thromboembolism, 6 occurred in patients who had warfarin deferred or withdrawn because of bleeding. There were 15 episodes of major bleeding (6.7%; 95% CI, 4.1 to 10.8): 8 occurred intraoperatively or early postoperatively before low-molecular-weight heparin was restarted, 5 occurred in the first postoperative week after low-molecular-weight heparin was restarted, and 2 occurred well after low-molecular-weight heparin was stopped. There were no deaths.

Conclusions— Bridging therapy with subcutaneous low-molecular-weight heparin is feasible; however, the optimal approach for the management of patients who require temporary interruption of warfarin to have invasive procedures is uncertain.


Key Words: blood vessel prosthesis • bridging therapy • fibrillation • heparin, low-molecular-weight


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