VTE Prevention: Is Aspirin Really That Good?
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.
Preventing VTE in Below-the-Knee Surgery
Venous thromboembolism (VTE) following hip fractures and hip/knee arthroplasty—both deep vein thrombosis (DVT) and pulmonary embolism (PE)—has been relatively well studied. We therefore have a fairly clear understanding what the risks for DVT and PE are with no treatment as well as with modern preventive chemotherapeutic agents. However, such clarity on the need for and effectiveness of VTE prophylaxis is lacking for below-the-knee (BTK) orthopaedic procedures. This is largely due to the fact that such procedures have been deemed “low risk”—despite a dearth of supporting evidence for that assumption. In the March 20, 2019 issue of The Journal, Heijboer et al. used a sophisticated propensity score matching methodology to evaluate the rate of VTE in >10,000 BTK surgery patients at their tertiary care referral center.
The authors evaluated patients who underwent orthopaedic surgery distal to the proximal tibial articular surface, including foot/ankle procedures, open reduction of lower-leg fractures, and BTK amputations. They performed propensity score matching to compare 5,286 patients who received any type of chemotherapeutic prophylaxis with the same number who did not, across several key risk categories. The good news is that VTE prophylaxis effectively lowered the risk of symptomatic DVT or PE from 1.9% to 0.7% (odds ratio of 0.38, p <0.001).
Unfortunately (but not surprisingly), this effectiveness came at the price of increased systemic or local bleeding among patients using chemical VTE prophylaxis, with an incidence of 1.0% in the no-prophylaxis group and 2.2% in the prophylaxis group (odds ratio of 2.18, p <0.001). The authors did not assess the incidence of deep infection or hematoma formation, which often accompany increased local bleeding. The low overall incidence of VTE and bleeding did not allow for subgroup analysis according to location of surgery, and aspirin use was not controlled for in their study. In addition, Heijboer et al. used hospital coding data, and the accuracy of the database was not assessed.
The authors recommend that “anticoagulant prophylaxis be reserved only for patient groups who are deemed to be at high risk for VTE,” but we still don’t know precisely who is at high risk among BTK surgery patients. It is my hope that these findings will prompt large, prospective multicenter trials in the foot and ankle community to better determine which types of patients should be exposed to an increased risk of postoperative bleeding complications in order to achieve a clinically important decreased risk of VTE with chemical prophylaxis.
Marc Swiontkowski, MD
JBJS Editor-in-Chief
Tranexamic Acid: Effective—and Safe—in THA
Prior research has established that total hip arthroplasty (THA), in and of itself, is associated with a small increased risk of venous thromboembolism (VTE). Hence the concern that routinely administering the antifibrinolytic drug tranexamic acid (TXA) perioperatively, as is commonly done nowadays to reduce blood loss during surgery, might further increase the risk of THA-related thromboembolic events. But the findings from a large population-based cohort study by Dastrup et al. in the October 17, 2018 JBJS, should allay many of those concerns.
The authors evaluated >45,000 Danish patients who had a THA between 2006 and 2013. Approximately 85% of those patients received intravenous TXA perioperatively, while the rest did not. Dastrup et al. evaluated adverse cardiovascular events (VTE, deep venous thrombosis, pulmonary embolism, myocardial infarction, and ischemic stroke) among those patients over 30 postoperative days, and they found no increased risk in any of those outcomes among the patients who received TXA relative to those who did not. These optimistic findings were essentially the same when the authors analyzed the data using a multivariable model and with propensity-score matching.
Dastrup et al. conclude that TXA in the setting of THA is safe with respect to VTE, and David Ayers, MD, commenting on the study, concurs. However, Dr. Ayers cautions that the study did not have the statistical strength to evaluate the potential cardiovascular risks of TXA in THA patients who have undergone previous cardiac procedures, such as stent placement. He therefore suggests that “further safety evaluation should be directed toward [such] patients at higher risk for complications after receiving TXA.”
Aspirin Noninferior to Rivaroxaban for Anticoagulation after Joint Replacement
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 khoshbinam@smh.ca.
What’s New in Adult Reconstructive Knee Surgery 2018, Part II
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
Meniscal Injuries
—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
References
- 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.
What’s New in Foot and Ankle Surgery
Every month, JBJS publishes a Specialty Update—a review of the most pertinent and impactful studies published in the orthopaedic literature during the previous year in 13 subspecialties. Click here for a collection of all OrthoBuzz Specialty Update summaries.
This month, OrthoBuzz asked Sheldon Lin, MD, co-author of the April 19, 2017 Specialty Update on foot and ankle surgery, to select the five most clinically compelling findings from among the more than 50 studies cited in the article.
VTE Prevention
–Recommendations for venous thromboembolism (VTE) prophylaxis in isolated foot and ankle fractures are conflicting. In a prospective study, Zheng et al.1 determined the incidence of VTE in 814 patients who received either low-molecular-weight heparin or placebo for 2 weeks postoperatively. The overall incidence of deep vein thrombosis was 0.98% in the heparin group and 2.01% in the placebo group, with no significant difference between the two. The risk factors were high body mass index (BMI) and advanced age. The authors concluded that routine chemical prophylaxis was not necessary in cases of isolated foot and ankle fractures.
Age and Total Ankle Arthroplasty
–Concerns regarding implant survivorship in younger patients have prompted investigations into the effect of age on total ankle arthroplasty outcomes. Demetracopoulos et al.2 prospectively compared patient-reported outcomes and revision rates in patients who were 70 years of age. At the 3.5-year follow-up, patients who were 70 years of age, although no differences were observed in pain, need for reoperation, or revision rates between groups.
Hallux Rigidus/Hallux Valgus
–Joint-preserving arthroplasties for hallux rigidus have been proposed as an alternative to first metatarsophalangeal joint arthrodesis. However, they have shown high rates of failure with associated bone loss, rendering salvage arthrodesis a more complicated procedure with worse outcomes. A Level-I study by Baumhauer et al.3 investigated the use of a synthetic cartilage implant that requires less bone resection than a traditional arthroplasty. Patients were randomized to implant and arthrodesis groups. At the 2-year follow-up, pain level, functional scores, and rates of revision surgical procedures were statistically equivalent in both groups. Secondary arthrodesis was required in <10% of the implant group and was considered to be a straightforward procedure because of preservation of bone stock.
–Hallux valgus surgical procedures are commonly performed under spinal, epidural, or regional anesthesia. Although peripheral nerve blocks have become increasingly popular with the advent of ultrasound, the associated learning curve has limited more widespread use. A Level-I study by Karaarslan et al.4 compared the efficacy of ultrasound-guided popliteal sciatic nerve blocks with spinal anesthesia in patients undergoing hallux valgus correction. The popliteal block group demonstrated decreased pain scores at every time point up to 12 hours postoperatively, longer time to first analgesic requirement, and increased patient satisfaction scores compared with the spinal anesthesia group. The popliteal block group also did not experience the adverse effects of hypotension, bradycardia, and urinary retention occasionally seen with spinal anesthesia.
Orthobiologics
–Orthobiologics continue to generate considerable interest within the orthopaedic community. Platelet-rich plasma and hyaluronic acid have been investigated as adjuncts to promote healing. In a Level-I study, Görmeli et al.5 randomized patients to receive platelet-rich plasma, hyaluronic acid, or saline solution injections following arthroscopic debridement and microfracture of talar osteochondral lesions. At the intermediate-term follow-up, the platelet-rich plasma and hyaluronic acid groups exhibited a significant increase in AOFAS scores and decrease in pain scores compared with the control group, with the platelet-rich plasma group showing the greatest improvement.
References
- Zheng X, Li DY, Wangyang Y, Zhang XC, Guo KJ, Zhao FC, Pang Y, Chen YX. Effect of chemical thromboprophylaxis on the rate of venous thromboembolism after treatment of foot and ankle fractures. Foot Ankle Int. 2016 Nov;37(11):1218-24.
- Demetracopoulos CA, Adams SB Jr, Queen RM, DeOrio JK, Nunley JA 2nd, Easley ME. Effect of age on outcomes in total ankle arthroplasty. Foot Ankle Int. 2015 Aug;36(8):871-80.
- Baumhauer JF, Singh D, Glazebrook M, Blundell C, De Vries G, Le ILD Nielsen D, Pedersen ME, Sakellariou A, Solan M, Wansbrough G, Younger AS, Daniels T; for and on behalf of the CARTIVA Motion Study Group. Prospective, randomized, multi-centered clinical trial assessing safety and efficacy of a synthetic cartilage implant versus first metatarsophalangeal arthrodesis in advanced hallux rigidus. Foot Ankle Int. 2016 May;37(5):457-69.
- Karaarslan S, Tekg¨ul ZT, S¸ ims¸ek E, Turan M, Karaman Y, Kaya A, Gönüllü M. Comparison between ultrasonography-guided popliteal sciatic nerve block and spinal anesthesia for hallux valgus repair. Foot Ankle Int. 2016 Jan;37(1):85-9. Epub 2015 Aug 20.
- Görmeli G, Karakaplan M, Görmeli CA, Sarıkaya B, Elmalı N, Ersoy Y. Clinical effects of platelet-rich plasma and hyaluronic acid as an additional therapy for talar osteochondral lesions treated with microfracture surgery: a prospective randomized clinical trial. Foot Ankle Int. 2015 Aug;36(8):891-900.
JBJS Editor’s Choice—VTE Risk with Metastatic Skeletal Lesions: Fix Prophylactically or Not?
In the February 15, 2017 issue of The Journal, Aneja et al. utilize a large administrative database to examine the critical question of venous thromboembolism (VTE) risk as it relates to managing patients with metastatic femoral lesions. The authors found that prophylactic intramedullary (IM) nailing clearly resulted in a higher risk of both pulmonary embolism and deep-vein thrombosis, relative to IM nailing after a pathologic fracture. Conversely, the study found that patients managed with fixation after a pathological fracture had greater need for blood transfusions, higher rates of postoperative urinary tract infections, and a decreased likelihood of being discharged to home.
The VTE findings make complete clinical sense, because when we ream an intact bone, the highly pressurized medullary canal forces coagulation factors into the peripheral circulation. When we ream after a fracture, the pressures are much lower, and neither the coagulation factors nor components of the metastatic lesion are forced into the peripheral circulation as efficiently, although some may partially escape through the fracture site.
One might conclude that we should never consider prophylactic fixation in the case of metastatic disease in long bones, but that would not be a patient-centric position to hold. In my opinion, the decision about whether to prophylactically internally fix an impending pathologic fracture should be based on patient symptoms and consultations with the patient’s oncologist and radiation therapist.
If all of the findings from Aneja et al. are considered, and if the patient’s symptoms are functionally limiting after initiation of appropriate radiation and chemotherapy, prophylactic fixation should be performed, along with vigilantly managed VTE-prevention measures. This study is ideally suited to inform these discussions for optimum patient care.
Marc Swiontkowski, MD
JBJS Editor-in-Chief
JBJS Reviews Editor’s Choice–VTED after Foot and Ankle Surgery
It seems that anytime a lower extremity undergoes operative treatment, the question is raised regarding the need for and type of thromboprophylaxis. However, controversy exists regarding the use of prophylaxis against venous thromboembolic disease (VTED) after foot and ankle surgery, largely because there are insufficient data from large-scale randomized trials to help guide foot and ankle surgeons in their decision-making processes. Currently, foot and ankle surgeons are forced to make decisions on the basis of incomplete information and contradictory guidelines. Moreover, there is inaccuracy in extrapolating findings from hip and knee arthroplasty studies to the foot and ankle population.
In the December 2015 issue of JBJS Reviews, Guss and DiGiovanni review VTED in the setting of foot and ankle surgery and recognize that certain patient populations may be at higher risk, including patients over the age of forty years with acute Achilles tendon ruptures, patients over the age of fifty years with ankle fractures, patients with diabetes mellitus, patients with connective-tissue inflammatory diseases, and patients with a history of VTED. They also consider associated factors such as the use of oral contraceptives, cigarette smoking, recent air travel, and a family history of VTED. They emphasize that there have been limited randomized controlled trials addressing the question of thromboprophylaxis after foot and ankle surgery and that current data suggest that the use of chemoprophylaxis against VTED in patients undergoing foot and ankle surgery may not necessarily lower the incidence of VTED events. Large-scale postoperative randomized trials are necessary to better guide foot and ankle surgeons in their decision-making processes regarding thromboprophylaxis after surgery. As a result, current foot and ankle surgeons continue to have to make decisions on the basis of incomplete information and contradictory guidelines.
In order to provide some clarity to these issues, specialty societies and associations, including the American College of Chest Physicians and the American Academy of Orthopaedic Surgeons, have issued recommendations regarding the appropriate use of prophylaxis against VTED in the postoperative period. However, these guidelines are largely based on literature of variable quality and applicability. For example, there is no agreement on the appropriate framework for risk-benefit analysis of these issues. Furthermore, unlike the American College of Chest Surgeons and the American Academy of Orthopaedic Surgeons, the American Orthopaedic Foot & Ankle Society has repeatedly expressed its inability to provide any guidance because of the lack of available information.
The literature examining the incidence of VTED after foot and ankle surgery is limited. Nevertheless, clinicians must make decisions against the backdrop of global quality initiatives that consider VTED to be a preventable event.
Thomas Einhorn, MD
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.
Thromboprophylaxis Unwarranted After Lower-Leg Fractures
The venographic prevalence of deep vein thrombosis in people with distal lower-extremity injuries that require surgery or casting ranges from 10% to 40%. But a prospective cohort study in the May 21, 2014 JBJS found that only 0.6% of 1200 patients with lower-leg fractures and no medical or mechanical thromboprophylaxis had symptomatic, objectively confirmed venous thromboembolism (VTE) over a 12-week follow-up. Moreover, none of the seven thrombotic complications was fatal. This leads the authors to conclude that “the risk-benefit ratio and cost effectiveness of routine anticoagulant prophylaxis are unlikely to be favorable for these patients.” They go on to say that despite the large sample size in this study, the low prevalence of VTE made it impossible to pinpoint characteristics that could identify a subgroup of similar patients who might be at higher risk of clotting problems.
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