FDA Approves Pradaxa for Thromboprevention After Hip Replacement
The FDA this week approved dabigatran (Pradaxa) for prevention of DVT and pulmonary embolism following hip arthroplasty surgery. The approval follows FDA analysis of two randomized phase 3 trials (RE-NOVATE and RE-NOVATE II) in which patients who took dabigatran experienced lower rates of venous thromboembolism and all-cause death than those who took enoxaparin. Conversely, those taking the higher dose of dabigatran (220 mg) had higher rates of major bleeding than those taking enoxaparin.
The FDA initially approved dabigatran to reduce the risk of stroke and embolism in patients with nonvalvular atrial fibrillation; the recent hip-replacement indication is the fourth in five years for this novel anticoagulant.
Perhaps most significantly for orthopaedists who now might prescribe dabigatran for hip-replacement patients, last month the FDA approved the first drug (idarucizumab, or Praxbind) to reverse the effects of dabigatran, possibly making the higher risk of bleeding with dabigatran less of a clinical concern.
JBJS Reviews Editor’s Choice–Orthopaedic Patients Taking Anticoagulants
Perioperative anticoagulation for patients undergoing orthopaedic surgery remains a challenge. Currently, there is insufficient evidence to provide definitive recommendations for care. Recent estimates suggest that, in the U.S. alone, there are over two million patients with atrial fibrillation who receive warfarin each year. Moreover, >100,000 heart valve replacements are performed annually.
In the September 2015 issue of JBJS Reviews, Dundon et al. review current recommendations for perioperative management of patients on existing anticoagulation therapy. They note that cessation of warfarin is based on risk stratification for thromboembolic events and bleeding risk, with cessation and bridging therapy being recommended if patients are at high risk for thromboembolic events or bleeding. On the basis of their assessment of published reports, they recommend that warfarin should be withdrawn and that bridging therapy should be instituted five days prior to surgery. Cessation and regular dosing should be resumed twelve to twenty-four hours after the operation.
However, the issue of perioperative bridging is currently under debate. The authors of this article could find no double-blind, randomized, controlled trials in which patients undergoing vitamin-K antagonist therapy who had received bridging with low-molecular-weight heparin or unfractionated heparin were compared with patients undergoing vitamin-K antagonist therapy who had received no bridging therapy. Bridging therapy with therapeutic-dose intravenous unfractionated heparin should be stopped four to six hours before surgery, but patients receiving therapeutic-dose subcutaneous low-molecular-weight heparin should take the last dose approximately twenty-four hours prior to surgery.
The authors recommended that patients in high cerebrovascular and cardiovascular risk groups should maintain aspirin with bridging therapy and may also maintain clopidogrel in emergencies as long as they are not undergoing a high-risk procedure. For patients who take rivaroxaban or dabigatran, emergency surgery is permissible as long as levels of the drug are ≤30 ng/mL at the time of admission.
These recommendations are based on careful and critical analyses of available data; however, as noted above, there are no critical evidence-based studies in the area of perioperative management of anticoagulation in patients who are undergoing orthopaedic surgery. The concepts and ideas presented in this article should be considered as recommendations at best.
Thomas Einhorn, Editor
JBJS Reviews
Aspirin’s Effectiveness in VTE Prevention Varies by Procedure
“Deep vein thrombosis of the right leg” by James Heilman, MD – Own work. Licensed under Creative Commons Attribution-Share Alike 3.0 via Wikimedia Commons
A recent meta-analysis of eight randomized trials (1,408 total patients) compared aspirin to anticoagulants such as warfarin and dabigatran for preventing venous thromboembolism (VTE) after hip and knee arthroplasty and hip-fracture repair. The analysis found that the overall prophylactic power of these two medical approaches was essentially equal following major lower-extremity surgery. However, the comparison, appearing in the Journal of Hospital Medicine, found a slightly higher (but statistically nonsignificant) risk of deep vein thrombosis (DVT) with aspirin following hip-fracture repair. Conversely, the risk of bleeding after hip-fracture surgery was lower with aspirin than with anticoagulants.
For additional insight into VTE prophylaxis, view the FREE recorded JBJS webinar “Preventing Arthroplasty-Associated Venous Thromboembolism.” Register here.
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