The effects of timing of prophylaxis, type of anesthesia, and use of mechanical methods on outcome in major orthopedic surgery - subgroup analyses from 17,701 patients in the XAMOS study

Abstract

PurposeReal-world data on the use of rivaroxaban in the perioperative period in patients undergoing major orthopedic surgery are limited. Subsets of data from the Phase IV, non-interventional XAMOS study were analyzed to explore the potential influence of timing of the first thrombo prophylactic dose, type of anesthesia, and concomitant mechanical prophylaxis on clinical outcomes in patients undergoing major orthopedic surgery in routine clinical practice.Patients and methodsIn XAMOS, 8,778 patients received rivaroxaban (10 mg once daily) and 8,635 received standard-of-care (SOC) pharmacological prophylaxis (safety population). Crude incidences of symptomatic thromboembolic and treatment-emergent bleeding events were analyzed according to timing of the first postoperative thromboprophylactic dose, use of general or neuraxial anesthesia, and use of mechanical prophylaxis with pharmacological thromboprophylaxis.ResultsIn the rivaroxaban group, the incidences of symptomatic thromboembolic events were 0.7%, 1.0%, and 0.7% in patients receiving the first thromboprophylactic dose at ≤6 hours, >6 hours to ≤10 hours, and >10 hours to ≤24 hours after surgery, respectively. In the SOC group, the incidence of symptomatic thromboembolic events was slightly higher when the postoperative dose was given at >10 hours to ≤24 hours (1.8% vs 1.1% at ≤6 hours and 1.3% at >6 hours to ≤10 hours). The antithrombotic effect of rivaroxaban was maintained in comparison to the SOC group. The incidence of major bleeding (RECORD trial definition) was low and similar between the two treatment groups and was not influenced by timing of the first thromboprophylactic dose. Neuraxial anesthesia was used more than any other form of anesthesia for both hip and knee surgery; the effectiveness of rivaroxaban was not influenced by the type of anesthesia used. No spinal hematomas were reported in patients receiving neuraxial anesthesia in either treatment group. Use of mechanical thromboprophylaxis in addition to rivaroxaban or SOC pharmacological prophylaxis did not reduce the risk of thromboembolic events further.ConclusionThe effectiveness and safety of rivaroxaban in patients undergoing major orthopedic surgery in routine clinical practice were maintained irrespective of timing of the first postoperative dose within 24 hours after surgery, the type of anesthesia, and the additional use of mechanical thromboprophylaxis.

Recommendations from the ICM-VTE: General

“…Larger studies have demonstrated a low incidence of EH. A 2016 phase IV, non-interventional study XareltoÒ in the prophylaxis of post-surgical venous thromboembolism after elective major orthopaedic surgery of hip or knee (XAMOS) by Haas et al 2067 , compared the safety and efficacy of rivaroxaban 10 mg to standard of care (LMWH, fondaparinux, or dabigatran) in patients who underwent major orthopaedic surgery. This study reported no cases of spinal hematoma in the neuraxial anesthesia patients (n = 10,355) regardless of postoperative anticoagulant timing.…”

Timing of Perioperative Pharmacologic Thromboprophylaxis Initiation and its Effect on Venous Thromboembolism and Bleeding Outcomes: A Systematic Review and Meta-Analysis

“…Three trials did report increased bleeding when thromboprophylaxis was initiated earlier perioperatively (eTable 5-7) 28,32,38 . There were 8 studies that reported mortality secondary to VTE or bleeding 16,17,22,27,28,30,34,41 . There were no fatal PEs or bleeding events in most of these studies 16,22,27,28,30,34 , however, 3 fatal PEs were reported in the Haas study (1 in the early preoperative initiation group and 2 in the later pre-operative initiation group) 41 and 5 fatal PEs were reported in the Du study (0 in the early post-operative initiation group, 1 in the late postoperative initiation group, and 4 in a group starting thromboprophylaxis at 72 hours postoperative) 17 .…”

What Surgeons Should Know About Non–Vitamin K Oral Anticoagulants

“…Therefore, it would seem reasonable that the same guidelines for stopping a NOAC before a high-risk surgery would apply equally to spinal and epidural anesthesia. Limited data from the Xarelto for VTE Prophylaxis After Hip or Knee Arthroplasty (XAMOS) and Regulation of Coagulation in Orthopaedic Surgery to Prevent Deep Vein Thrombosis and Pulmonary Embolism (RECORD) studies suggest that postoperative risk of bleeding with resumption of NOAC therapy is not affected by type of anesthesia, including neuraxial. However, the most recent guidelines from the American Society of Regional Anesthesia and Pain Medicine suggest withholding dabigatran therapy for 4 to 5 days before spinal or epidural anesthesia and a minimum of 3 days for apixaban and rivaroxaban .…”