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
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.
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.
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
Among the topics that consistently stimulate debate among orthopaedic surgeons is the treatment of acute Achilles tendon rupture. The central question is typically, “Should this injury be treated operatively or nonoperatively?” In the April 2015 issue of JBJS Reviews, Guss et al. tackle this question.
The decision to treat acute Achilles tendon rupture has always been a trade-off between wound complications (associated with operative treatment) and the risk of rerupture (associated with both nonoperative and operative treatment but more commonly associated with nonoperative treatment). While the authors quote numerous reports, an important observation among all of the reports cited is that rehabilitation protocols for nonoperative treatment were not uniform across cohorts. Considering recent findings, the debate about operative vs. nonoperative intervention apparently has shifted from a focus on rerupture and infection to a focus on functional outcomes. Functional rehabilitation protocols have decreased the rerupture rate historically seen in association with the nonoperative treatment of these injuries. Operative treatment may provide some functional benefits, but recent studies suggest that many of these benefits are transient or subtle.
Guss at al. also point out that the rate of deep-vein thrombosis after Achilles tendon rupture may be higher than that observed in association with many other foot and ankle conditions. Indeed, the incidence of deep-vein thrombosis in patients with acute Achilles tendon rupture is possibly as high as one in three, but the vast majority of deep-vein thromboses are asymptomatic and are unlikely to be clinically relevant. Prophylactic anticoagulation should be considered for older patients with Achilles tendon rupture, including those managed nonoperatively, as well as for patients with other known risk factors.
In summary, recent reports have suggested that the use of functional rehabilitation in lieu of cast immobilization has, to a certain extent, reduced the higher rates of rerupture that historically have been associated with nonoperative treatment. Moreover, functional rehabilitation protocols are not associated with the wound complications that are inherently associated with operative repair. Operative repair may provide functional benefits, but reports have suggested that these benefits may be transient or incremental and limited to those patients who participate in more intense athletic endeavors. Indeed, more research with well-designed, randomized clinical trials is necessary to clarify the potential for incremental functional gain following operative repair as well as to identify those patients in whom nonoperative treatment is more likely to fail.
Thomas A. Einhorn, MD, Editor
Click here for another OrthoBuzz post about this JBJS Reviews article.
The fact that 12 of the 16 AAOS clinical practice guidelines for treating Achilles tendon ruptures are supported by “weak” or “inconclusive” evidence makes the recent JBJS Reviews article by Guss et al. on this subject all the more welcome.
The most emphatic point made by these authors is that functional rehabilitation protocols with early motion (and an associated shift away from long-term post-injury immobilization) have made a dent in the re-rupture rates historically seen with nonoperative treatment of Achilles tendon injuries, the incidence of which has increased in recent decades. The authors emphasize, however, that the delicate balance between loading and unloading of a healing Achilles tendon remains a rehabilitative challenge, and they encourage further research to identify which patients are more or less likely to experience success with nonoperative management.
The authors note also that the focus of outcomes research of different management methods has shifted from rates of re-rupture and infection to more specific functional measures—and, in some cases, to direct and indirect cost measures. For example, Guss et al. cite one meta-analysis that found that operatively treated patients returned to work almost three weeks earlier than those treated nonoperatively.
The authors also observe that the rate of deep vein thrombosis after Achilles rupture seems to be higher than that seen in other foot/ankle conditions, but they add that the majority of those thrombotic events are “unlikely to be clinically important.” Still, Guss et al. conclude that “prophylactic anticoagulation should be considered for older patients with an Achilles tendon rupture, including those treated nonsurgically.”