OrthoBuzz occasionally receives posts from guest bloggers. In response to a three recent studies, the following commentary comes from Jeffrey B. Stambough, MD.
Throughout the last decade, we’ve experienced a boom in anticoagulation options to help prevent venous thromboembolism (VTE) associated with orthopaedic procedures. The use of aggressive anticoagulation, such as warfarin and various heparin formulations, is being questioned, largely due to concerns about bleeding risks and wound complications. Along with the newer direct oral anticoagulants such as rivaroxaban, over-the-counter aspirin (ASA) is gaining prominence as an anticoagulant due to its high efficacy, low cost, convenience for patients, favorable side-effect profile, and cardioprotective attributes. Current guidelines include the use of all these thromboprophylactic agents, but three recent studies lend credence to using aspirin as the primary VTE prophylactic agent when performing total joint arthroplasty (TJA).
In a March 20, 2019 JBJS study analyzing >31,000 TJAs performed at a single institution over 17 years, Rondon et al. found a 3-fold lower 30-day and 2-fold lower 1-year mortality rate in patients receiving ASA (81mg or 325 mg twice daily), compared to those who received non-aspirin thromboprophylaxis (mainly warfarin). No mortality differences were noted between the two ASA dosing regimens. While investigating specific causes of death, the authors discovered that the primary cause of death in the non-ASA cohort was cardiac related at all time points.
A second study, from the April 3, 2019 JBJS, looked into the effects of 3 antithrombotic agents on symptomatic VTE rates and periprosthetic infections in high-risk patients undergoing primary or revision TJA. When compared to the two more potent agents (warfarin and low-molecular-weight heparin), ASA proved more effective at reducing pulmonary embolism (PE) and VTE rates in high-risk patients, and it was also associated with lower rates of periprosthetic joint infection when compared with warfarin. Thus, it seems that even in patients deemed to be higher risk for developing VTE, ASA may be a safe, effective option.
Lastly, Runner et al. gleaned VTE prophylaxis data from >22,000 TJA cases submitted by surgeons sitting for Part 2 of ABOS between 2014 and 2016. The findings, reported in the April 2019 issue of the Journal of Arthroplasty, showed similar trends to those seen in the two previously mentioned studies: Mild (distal or superficial deep vein thrombosis [DVT]), moderate (nonfatal PE, proximal DVT) and severe (fatal PE) VTE events, as well as death, were significantly less frequent in those who received ASA compared to more aggressive agents (heparin or one of its analogs, direct oral agents, or warfarin). Also, patients who received ASA with or without mechanical prophylaxis had significantly lower complication rates (95.5% vs. 93.0%, p<0.001).
One firmly held dogma in medicine is that patients who are at higher risk for VTE should be treated with stronger anticoagulation medications. However, these 3 studies support the idea that less aggressive anticoagulation medication (specifically, low-dose aspirin) may be the more effective and safer option for most patients. In our ongoing quest to improve patient outcomes and mitigate risk around the TJA episode, we should consider using aspirin for thromboprophylaxis unless there is an explicit contraindication in a specific patient.
However, we should also keep in mind that these three studies have the common limitations of all retrospective analyses. Recent randomized trials have shown aspirin to be “noninferior” to other anticoagulants for VTE prevention, and in less than 2 years, we should have even more definitive answers to this question from the randomized, multicenter PEPPER trial, with its estimated 25,000 participants.
Jeffrey B. Stambough, MD is an orthopaedic hip and knee surgeon, an assistant professor of orthopaedic surgery at University of Arkansas for Medical Sciences, and a member of the JBJS Social Media Advisory Board.
OrthoBuzz occasionally receives posts from guest bloggers. This guest post comes from Amir Khoshbin, MD in response to a recent randomized trial in the New England Journal of Medicine.
The ideal anticoagulation protocol for patients who have received a total knee or hip replacement remains controversial. Results from the recently published “Extended Venous Thromboembolism Prophylaxis Comparing Rivaroxaban to Aspirin Following Total Hip and Knee Arthroplasty (EPCAT) II” trial add some clarity to this topic.
This large double-blind, randomized noninferiority trial compared two outpatient anticoagulation regimens after elective unilateral primary or revision hip or knee arthroplasty. Almost 3,500 patients were enrolled, and they all received 10 mg of rivaroxaban daily until postoperative day five. After that, 1,707 patients were randomized to receive 81 mg of aspirin daily, while the remaining 1,717 patients received 10 mg of rivaroxaban daily. Per previous recommendations, total knee arthroplasty patients received anticoagulation for a total of 14 days, and total hip arthroplasty patients continued anticoagulation for 30 days.
Twelve patients in the rivaroxaban group (0.7%) had a venous thromboembolism event in the 90-day postsurgical period, versus 11 patients (0.64%) in the aspirin group (p >0.05). In terms of complications from anticoagulation treatment, 5 patients (0.29%) in the rivaroxaban group and 8 patients in the aspirin group (0.47%) had a major bleeding event (p >0.05). It is worth noting that there were multiple different implants, approaches, and perioperative protocols followed in the study. Also, very few patients with a history of venous thromboembolism (81 patients, 2.4%), cancer (80 patients, 2.3%) or smoking (319 patients, 9.3%) were included in the study. These patients would be considered at higher risk for venous thromboembolism after joint replacement.
These limitations notwithstanding, the results from prophylaxis with aspirin after an initial five days of rivaroxaban were not significantly different from results with continued rivaroxaban. Institutional prices vary, but in this time of bundled care, the financial implications of studies like this one could be great. Anecdotally, in our institution the price of rivaroxaban is 140 times that of aspirin.
This is not the first study whose findings support the use of aspirin for venous thromboembolism prophylaxis, but it is one of the largest. It appears that such findings are starting to change the practice of some orthopaedic surgeons. We expect that additional large studies will provide further insight into this question.
Amir Khoshbin, MD is an assistant professor of orthopaedics at the University of Toronto and a member of the JBJS Social Media Advisory Board. He can be reached at email@example.com.
Previously this month, Chad A. Krueger, MD, JBJS Deputy Editor for Social Media, selected what he deemed to be the most clinically compelling findings from among the more than 150 studies cited in the January 17, 2018 Specialty Update on Adult Reconstructive Knee Surgery. In this OrthoBuzz post, Gwo-Chin Lee, MD, author of the Specialty Update on Adult Reconstructive Knee Surgery, selects his “top five.”
Nonoperative Knee OA Treatment
—Atukorala et al. found a significant dose-response relationship between all KOOS subscales and percentage of weight change across all weight-change categories. Participants required ≥7.7% of weight loss to achieve a minimal clinically important improvement in function.1
—A prospective cohort study showed that patients undergoing arthroscopic procedures for degenerative meniscal tears did not have clinically meaningful differences in outcomes compared with patients with traumatic meniscal tears.2
Postoperative Pain Management
—Authors of a Cochrane Systematic Review ascertained that liposomal bupivacaine at the surgical site appears to reduce postoperative pain compared with placebo. However, because of the low quality and volume of evidence, it is not possible to determine its effect compared with conventional agents.3
Avoiding Post-TKA Complications
—In a randomized trial, the use of a tourniquet resulted in upregulation of peptidase activity within the vastus medialis but did not result in an increase in muscular degradation products. The authors concluded that the relationship between tourniquet-induced ischemia and muscle atrophy is complex and poorly understood.4
—The authors of a registry study found no evidence that fondaparinux, enoxaparin, or warfarin are superior to aspirin in the prevention of PE, DVT, or VTE—or that aspirin is safer than these alternatives. However, enoxaparin is as safe as aspirin with respect to bleeding, and fondaparinux is as safe as aspirin with respect to risk of wound complications.5
- Atukorala I, Makovey J, Lawler L, Messier SP, Bennell K, Hunter DJ. Is there a dose-response relationship between weight loss and symptom improvement in persons with knee osteoarthritis? Arthritis Care Res (Hoboken). 2016 Aug;68 (8):1106-14.
- Thorlund JB, Englund M, Christensen R, Nissen N, Pihl K, Jørgensen U, Schjerning J, Lohmander LS. Patient reported outcomes in patients undergoing arthroscopic partial meniscectomy for traumatic or degenerative meniscal tears: comparative prospective cohort study. BMJ. 2017 Feb 2;356:j356.
- Hamilton TW, Athanassoglou V, Mellon S, Strickland LH, Trivella M, Murray D, Pandit HG. Liposomal bupivacaine infiltration at the surgical site for the management of postoperative pain. Cochrane Database Syst Rev. 2017 Feb 1;2:CD011419.
- Jawhar A, Hermanns S, Ponelies N, Obertacke U, Roehl H. Tourniquet-induced ischaemia during total knee arthroplasty results in higher proteolytic activities within vastus medialis cells: a randomized clinical trial. Knee Surg Sports Traumatol Arthrosc. 2016 Oct;24(10):3313-21. Epub 2015 Nov 14.
- Cafri G, Paxton EW, Chen Y, Cheetham CT, Gould MK, Sluggett J, Bini SA, Khatod M. Comparative effectiveness and safety of drug prophylaxis for prevention of venous thromboembolism after total knee arthroplasty. J Arthroplasty. 2017 Nov;32(11):3524-28.e1. Epub 2017 May 31.
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
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.