Prevention of venous thromboembolism in the orthopedic surgery patient
ABSTRACT
Patients undergoing major orthopedic surgery—hip or knee arthroplasty, or hip fracture repair—are in the highest risk category for venous thromboembolism (VTE) solely on the basis of the orthopedic procedure itself. Despite this, nearly half of patients undergoing these procedures do not receive appropriate prophylaxis against VTE, often due to a disproportionate fear of bleeding complications in this population. Guidelines from the American College of Chest Physicians (ACCP) provide evidence-based recommendations for many aspects of VTE risk reduction in the setting of orthopedic surgery, as detailed in this review. The ACCP recommends the use of either low-molecular-weight heparin (LMWH), fondaparinux, or adjusted-dose warfarin as preferred VTE prophylaxis in patients undergoing either hip or knee arthroplasty. Fondaparinux is the preferred recommendation for patients undergoing hip fracture repair, followed by LMWH, unfractionated heparin, and adjusted-dose warfarin as alternative options. Extended-duration prophylaxis (for 4 to 5 weeks) is now recommended for patients undergoing hip arthroplasty or hip fracture repair. Patients undergoing knee arthroscopy do not require routine pharmacologic VTE prophylaxis.
SUMMARY
VTE in patients undergoing major orthopedic surgery is a serious health problem that is highly preventable, yet VTE prophylaxis remains underused in this patient population. Despite the availability of practice guidelines for VTE prevention in the orthopedic surgery setting, recommendations are not widely implemented in clinical practice. Recommended prophylactic options differ somewhat among various orthopedic procedures, and the supportive evidence differs for various anticoagulant options.
DISCUSSION: ADDITIONAL PERSPECTIVES FROM THE AUTHORS
Dr. Jaffer: The ACCP recommends against the routine use of aspirin as primary prophylaxis against VTE in major orthopedic surgery, yet orthopedic surgeons across the country still continue to use aspirin in this setting. What are your thoughts on this, Dr. McKean?
Dr. McKean: We agree with the ACCP’s recommendation against aspirin as primary VTE prophylaxis in orthopedic patients. The percentage of US knee arthroplasty patients who develop VTE after receiving no prophylaxis at all is roughly 64%; this percentage declines only slightly (to 56%) for knee arthroplasty patients who receive prophylaxis with aspirin.25 Since we clearly want to reduce VTE risk as much as possible, I would not use aspirin alone. I would use it only if the patient were already on aspirin, but then I would add either LMWH or fondaparinux.
Dr. Jaffer: Warfarin is another agent that is widely used for prophylaxis in major orthopedic surgery. In fact, the large registries of VTE prevention in major orthopedic surgery suggest that the use of warfarin may be slightly higher than the use of LMWH. If clinicians choose to use warfarin in their practice, what are your recommendations, Dr. Deitelzweig?
Dr. Deitelzweig: As primary prophylaxis for orthopedic surgery patients, warfarin must be dosed to achieve an INR of 2.0 to 3.0; the need for a value in this range is unequivocal. This is a challenging target to attain in the hospital setting.
Dr. Brotman: A study I was involved with a few years ago suggested that warfarin may be inadequate for VTE prevention in the first few days after orthopedic surgery.26 Orthopedic surgeons at the Cleveland Clinic, where I was practicing at the time, routinely used systematic ultrasonography to assess for thrombosis on postoperative day 2 or 3 following hip or knee arthroplasty, so we conducted a secondary analysis of a case-control study in these ultrasonographically screened arthroplasty patients to assess rates of early VTE and look for any associations with the type of prophylaxis used. We found that there was about a tenfold increase in the risk of VTE, both distal and proximal, on postoperative day 2 or 3 among patients who received warfarin compared with those who received LMWH. We concluded that warfarin’s delayed antithrombotic effects may not provide sufficient VTE prophylaxis in the immediate postoperative setting.26
Dr. Deitelzweig: That’s a good point. Although it’s important to achieve a therapeutic level of warfarin, we now have evidence that it takes some time to achieve that level, and in the interim, bad things can happen to patients.
Dr. Jaffer: Orthopedic surgery encompasses several types of procedures. Dr. Amin, which specific orthopedic surgery patients stand to benefit from extended prophylaxis, and how long should extended prophylaxis last?
Dr. Amin: Major orthopedic surgery comprises hip fracture repair, total hip replacement, and total knee replacement. For hip fracture, there are strong data to support the use of extended prophylaxis with fondaparinux 2.5 mg/day, which showed about an 88% relative reduction in the risk of symptomatic VTE compared with standard-duration fondaparinux (6 to 8 days) followed by matching placebo for the extended phase.27 The total duration of fondaparinux therapy in the extended-duration arm was 4 to 5 weeks.
Likewise, data support extended prophylaxis in hip arthroplasty patients, for whom the recommended duration is also 4 to 5 weeks. The systematic review by Hull et al17 demonstrated a 0.41 relative risk of DVT with extended-duration LMWH prophylaxis versus placebo in hip replacement patients (Figure 1), which was a highly statistically significant result.
In contrast, we do not yet have good data to support extended prophylaxis for patients undergoing total knee replacement, which is a bit surprising. In this setting, prophylaxis is recommended for 7 to 14 days but not beyond that.
Dr. Jaffer: Arthroscopy is probably the most common orthopedic procedure performed in the United States today. Dr. Brotman, what is the role of prophylaxis in patients undergoing arthroscopy?
Dr. Brotman: Minor surgery such as arthroscopy can typically be performed safely without routine prophylaxis, other than having the patient ambulate as soon as possible after the procedure. There may be exceptions to this rule, however. I believe that there is potentially a role for pharmacologic prophylaxis in arthroscopy patients who have major risk factors for VTE, such as a personal history of VTE, or who are not expected to become mobile again in a normal rapid fashion after the operation, but prophylaxis has not been studied systematically in such patients.
Dr. Jaffer: Dr. Spyropoulos, there are several new anticoagulants in the pipeline, specifically agents such as the oral direct factor Xa inhibitors and the direct thrombin inhibitors. What do recent clinical trials suggest with regard to the efficacy of these two drug classes for thromboprophylaxis in major orthopedic surgery?
Dr. Spyropoulos: The agents with the most available data are the oral direct factor Xa inhibitors apixaban and rivaroxaban and the oral direct thrombin inhibitor dabigatran. For prophylaxis in orthopedic surgery populations, phase 2 studies have been completed for apixaban and phase 3 trials have been completed for rivaroxaban and dabigatran.
It appears that the factor Xa inhibitors, apixaban and rivaroxaban, are efficacious in comparison with both adjusted-dose warfarin and LMWH, which is the gold standard for this group of patients.28,29 So these indeed appear to be promising agents. Rivaroxaban has been submitted to European regulatory agencies for approval for the prevention of VTE in patients undergoing major orthopedic surgery, and its developer plans to submit it to the FDA in 2008 for a similar indication in the United States.
The data are more equivocal with dabigatran. There have been several positive phase 3 studies in orthopedic surgery comparing two dabigatran dosing schemes, 150 and 220 mg once daily, with the European regimen of enoxaparin (40 mg once daily),30 but a recent study that compared these doses with the North American enoxaparin regimen (30 mg twice daily) failed to meet the criteria for noninferiority.31 Further clinical trial development is necessary for dabigatran, although in January 2008 the European Medicines Agency recommended its marketing approval for thromboprophylaxis in patients undergoing orthopedic procedures.32
I believe that in the next 3 to 5 years our armamentarium will see the addition of at least one, if not more, of these new agents that offer the promise of oral anticoagulation with highly predictable pharmacokinetics and pharmacodynamics and no need for monitoring.
