-Author name in bold denotes the presenting author
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424 Double Blind Randomized Control Trial of Postoperative Low Molecular Weight Heparin Bridging Therapy for Patients Who Are at High Risk for Arterial Thromboembolism (PERIOP 2)Clinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 332. Antithrombotic Therapy: Management of Challenging Patients and Scenarios
Hematology Disease Topics & Pathways:
Therapies, Clinically relevant
Sunday, December 2, 2018: 5:15 PM
Room 33B (San Diego Convention Center)

Michael J. Kovacs, MD1, Marc Rodger, MD, MSc2, Philip S. Wells, MD, MSc, FRCP3, Shannon M. Bates, MD, FRCPC, MSc4, Clive Kearon, MB, PhD5, Mark Blostein, MD FRCPC6*, Alejandro Lazo-Langner, MD, MSc7, Susan Kahn, MD8, Sam Schulman, MD, PhD, FRCPC9, Elham Sabri, MSc10*, Susan Solymoss, MD11, Timothy Ramsay, PhD12*, Luljeta Pallaveshi, RN, BA13* and David Anderson, MD14

1London Health Sciences Center -Victoria Hospital, London, ON, Canada
2Ottawa Hospital General Campus, Ottawa, ON, CAN
3Department of Medicine, Ottawa Hospital General Site, Ottawa, ON, Canada
4Division of Hematology, Department of Medicine, McMaster University, Hamilton, ON, Canada
5McMaster University, Juravinski Hospital and Cancer Center, Hamilton, ON, CAN
6Jewish General Hospital, Montreal, QC, CAN
7Department of Medicine, Division of Hematology, London Health Sciences Center, London, ON, Canada
8Center for Clinical Epidemiology and Community Studies, Montreal, QC, CAN
9Department of Medicine, Division of Hematology and Thromboembolism, Department of Obstetrics and Gynecology, The First I.M. Sechenov Moscow State Medical University, Russia, Hamilton, Canada
10Ottawa Health Research Institute (OHRI), Ottawa, QC, Canada
11St. Mary's Hospital Center, McGill University, Montreal, QC, Canada
12Ottawa Hospital Research Institute, Ottawa, ON, Canada
13London Health Sciences Centre, London, ON, Canada
14Dalhousie Unv. and Capital District, Halifax, NS, CAN

Background

It remains uncertain if patients with atrial fibrillation or mechanical heart valves requiring interruption of warfarin for procedures benefit from post-procedure anticoagulant bridging therapy.

Methods

In order to determine the efficacy and safety of postoperative LMWH bridging, we conducted a multicenter randomized double-blind controlled trial of patients with atrial fibrillation or a mechanical heart valve who require interruption of warfarin for a planned procedure. We excluded patients with active bleeding within 30 days, platelet count <100 x10⁹/L, spinal, cardiac or neurosurgery, life expectancy <3months, creatinine clearance <30ml/min, multiple mechanical valves or a Starr-Edwards valve, mechanical valve with history of stroke or TIA, or a history of heparin induced thrombocytopenia. The last dose of warfarin was given 6 days prior to the procedure. All patients received pre-procedure bridging therapy with dalteparin 200 IU per kilogram (max 18,000 IU) subcutaneously in the morning day-3 and day-2 then dalteparin 100 IU per kilogram (max 18,000 IU) subcutaneously 24 hours pre-procedure. Warfarin was resumed in the evening of the procedure at twice the usual dose for the first two days and then titrated according to INR. After the procedure (same day or next day), when hemostasis had been achieved, patients were randomized to receive dalteparin or placebo for at least 4 days and until the INR was greater than 1.9. Randomization was stratified by presence of a mechanical valve, by the post-procedure risk for major bleeding, and by centre. For patients at high risk for post-procedure major bleeding, dalteparin or placebo was administered at a fixed daily dose of 5000 IU. For patients at low risk for post-procedure major bleeding, dalteparin or placebo was administered at a daily dose of 200 IU per kilogram (max 18,000 IU). The primary analysis was a comparison of the proportion of patients who had major thromboembolism (stroke, proximal DVT, PE, MI, peripheral embolism) over 90 days by Chi-squared test according to the intention to treat principle. Secondary outcomes were major bleeding, all cause mortality and a composite outcome of major thromboembolism and major bleeding.

Results

Starting in October 2006 we randomized a total of 1471 patients of whom 1167 had atrial fibrillation (without mechanical heart valves) and 304 had mechanical valves (99 also had atrial fibrillation). Last follow up was completed in May 2016. Baseline characteristics were similar between the LMWH and the placebo groups (see Table 1). Due to a randomization program system error at two centres more atrial fibrillation patients were randomized to dalteparin rather than to placebo. Major thromboembolism occurred in 6/820 (0.71%) dalteparin patients and 7/650 (1.11%) placebo patients. Major post-procedure bleeding occurred in 12 (1.46%) dalteparin patients and 16 (2.46%) placebo patients. Findings were similar in patients with atrial fibrillation alone and in patients with mechanical heart valves (with or without atrial fibrillation) (Table 2).

Conclusions

In patients with atrial fibrillation and/or mechanical heart valves who had warfarin interrupted for a procedure there was no benefit from post-procedure LMWH bridging.

Disclosures: Kovacs: Bayer: Research Funding; Daiichi Sankyo Pharma Development: Research Funding. Wells: BMS: Honoraria, Research Funding; Sanofi: Honoraria; Janssen: Honoraria; Bayer: Honoraria. Bates: Eli Lilly Canada/May Cohen Chair in Women's Health: Other: unencumbered salary support (Eli Lilly Canada does not manufacture anticoagulants or antithrombotic agents); Bayer, Inc.: Other: site investigator for sponsored study, “Phase III, Multicentre, randomized trial to compare rivaroxaban with placebo for the treatment of symptomatic leg superficial vein thrombosis” (study funding to institution, no direct payments received). Kahn: Co-Principal Investigator on CanVECTOR, a pan-Canadian VTE research network that is funded by the Canadian Institutes of Health Research (CIHR) and unrestricted funds from a number of not-for-profit and industry funding partners: Research Funding; Aspen, Sanofi, BMS-Pfizer: Other: Advisory board. Schulman: Daiichi-Sankyo: Honoraria; Boehringer-Ingelheim: Honoraria, Research Funding; Sanofi: Honoraria; Bayer: Honoraria.

*signifies non-member of ASH