It is estimated that 300,000 to 600,000 Americans are affected each year by VTE, making it the third leading vascular diagnosis behind heart attack and stroke, and the leading cause of death due to major orthopedic surgery. Common causes for VTE are surgery, cancer, immobilization, or hospitalization. The risk of VTE is the highest for patients undergoing major orthopedic surgery, such as total knee arthroplasty (TKA), total hip arthroplasty (THA), or hip fracture surgery (HFS). Without appropriate prophylaxis, rates of VTE among these patients have been estimated to be as high as 60%. 124 Given that major orthopedic surgeries typically occur among older adults, the Centers for Medicare & Medicaid Services (CMS) has made the prevention and treatment of VTE a priority among their quality improvement efforts, such as through programmatic measure inclusion and harm area prioritization in initiatives. Accreditation organizations have followed suit, with the Joint Commission and the National Committee for Quality Assurance including measures for VTE treatment and prevention in their hospital accreditation and certification programs. Aspirin for VTE prophylaxis As VTE, in particular DVT, can be very difficult to diagnose, actively employing prevention techniques is critical to ensuring patient safety. Prevention methods include both mechanical and pharmacologic prophylaxis. Mechanical prophylaxis includes the use of compression devices, such as stockings and foot pumps. Pharmacologic prophylaxis is available via a number of different anticoagulant and antiplatelet drugs, including heparin derivatives, vitamin K antagonists, direct thrombin inhibitors, direct factor Xa inhibitors, and aspirin. There are two different types of pharmacologic agents available for VTE prophylaxis— anticoagulants and antiplatelets. Aspirin is an antiplatelet, and while there are other antiplatelets used for other cardiovascular conditions, these are not recommended for use in VTE prophylaxis. There is slight variation in existing guidelines regarding the use of aspirin for pharmacologic prophylaxis. The American Society of Hematology (ASH) the American College of Chest Physicians (ACCP), and the American Academy of Orthopedic Surgeons (AAOS) all recommend pharmacologic prophylaxis and/or mechanical prophylaxis for patients undergoing THA, TKA, or HFS. ASH and AAOS further recommend that patients receive both forms of prophylaxis, particularly patients who are at an increased risk for VTE. However, ASH and ACCP provide a list of recommended pharmacologic agents that specifically includes aspirin, whereas AAOS does not make recommendations regarding specific pharmacologic agents. Further, ACCP recommends low molecular weight heparin (LMWH) over other pharmacologic prophylaxis agents, whereas other guidelines have not made such a specific recommendation statement specifying the use of one type of pharmacologic prophylaxis agent over another.
Many hospitals include the use of aspirin in their surgical protocols for patients undergoing major orthopedic surgery. For prescribing surgeons, its use is at their discretion based on guideline recommendations, perceived patient risk, and the need to balance prevention with safety concerns, such as bleeding risk. This balance has become increasingly important as a growing number of studies have found that newer anticoagulant drugs are associated with a higher incidence of bleeding than prophylaxis agents. Aspirin as sole prophylaxis treatment In a comprehensive analysis of available pharmacologic prophylaxis options, Agaba et al. (2017) conducted a retrospective review of patients undergoing THA using a nationwide private and Medicare insurance database. 125 Patients studied received either aspirin alone or one of five anticoagulants. The analysis found that patients given aspirin alone had a significantly lower rate of both DVT and PE at 30 and 90 days following surgery, with an insignificant bleeding risk. Following a review of the effectiveness and safety side effects of each of the pharmacologic agents included in the study, the authors concluded that while rivaroxaban and fondaparinux have lower bleeding and thromboembolic events compared with other newer anticoagulants, aspirin also meets these criteria. In addition, aspirin is an easy-to-use, inexpensive option for prophylaxis following THA. Aspirin combined with other pharmacologic prophylaxis Several studies address the use of aspirin in combination with other pharmacologic prophylactic agents. For example, Anderson et al. (2018) conducted a double-blind randomized controlled trial at 15 university-affiliated health centers in Canada. 126 Patients undergoing elective unilateral primary or revision hip or knee arthroplasty received once-daily oral rivaroxaban for the first 5 days following surgery, and then were randomized to either continue the course of rivaroxaban or switch to aspirin for the next 9 days after TKA, or 30 days after THA. Findings indicate that aspirin is not worse (p<0.001) but not better than continued use of rivaroxaban. Additionally, there was not a significant difference in bleeding between the two groups (p=0.43). Hamilton et al. (2012) conducted a retrospective review of patients receiving aspirin prophylaxis after primary hip and knee arthroplasties. 127 Patients received a course of enoxaparin during their inpatient stay, followed by a course of aspirin for 28 days following discharge. Patients were compared with a control group that first received enoxaparin for 2 weeks following discharge before receiving a course of aspirin for a further 2 weeks. Researchers concluded that a protocol of only inpatient enoxaparin and then aspirin post discharge was both safe and effective in standard-risk patients.
Aspirin combined with mechanical prophylaxis Many studies have evaluated the use of an anticoagulant or antiplatelet in combination with other mechanical prophylaxis methods and most conclude that aspirin is safe and effective when used this way. For example, Deirmengian et al. (2016) conducted a retrospective review of patients undergoing TJA. 128 All patients received mechanical prophylaxis and then either warfarin (n=2463) or aspirin (n=534). The study found that the differences between the groups with regard to DVT or PE alone were not statistically significant (p=0.15; p=0.06, respectively). Fisher’s exact test showed a significantly higher risk for any symptomatic VTE in patients receiving warfarin (43 events, 1.75%) compared with patients receiving aspirin (3 events, p=0.03). Aspirin dosing considerations In their retrospective analysis, Faour et al. (2018) analyzed the medical records of patients receiving aspirin twice daily for 4 to 6 weeks following TKA. 129 Patients received low-dose, 81 mg, aspirin (n=1,327) or standard-dose, 325 mg (n=2,903). Analysis concluded that aspirin is safe and effective but that there was a significant difference in the incidence of VTE and DVT between the two groups (p=0.02 and p<0.001, respectively), with those receiving a standard dose experiencing a higher incidence of VTE and DVT (1.5% vs. 0.7% and 1.4% vs. 0.3%). However, there was not a significant difference in the incidence of PE (p=0.13), and a regression analysis showed no correlation between aspirin doses and the incidence of VTE (both DVT and PE) or DVT alone (p=0.94 and 0.20). Further, there is no statistically significant difference in the incidence of gastrointestinal (GI) or wound bleeding (p=0.62). Faour et al. reached similar conclusions when conducting the same retrospective analysis for patients undergoing THA. Unintended consequences There are a number of potential unintended consequences associated with the use of aspirin for VTE prophylaxis. Generic aspirin is widely available and significantly cheaper than alternative medications. Additionally, administrative costs are lower than with some alternative pharmacologic prophylaxis agents that require intravenous delivery or ongoing laboratory monitoring, such as with warfarin. Ease of administration may in turn have a positive impact on patient quality of life during the treatment period and support medication adherence. As with other pharmacologic prophylaxis agents, there is the potential risk that patients prescribed aspirin following major orthopedic surgery will experience operative site or major bleeding. The analysis of the incidence of these events was a priority for many of the articles included in this review. Twenty- three of the studies specifically addressed unintended patient safety outcomes in their analysis and conclusions. Of those, 22 concluded that overall aspirin was safer than other pharmacologic options, or had comparable risk.
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