ASH Clinical News ACN_4.5_FULL_ISSUE_DIGITAL - Page 26

Literature Scan New and noteworthy research from the medical literature landscape Aspirin as Effective as Rivaroxaban for Preventing VTE After Total Hip or Knee Arthroplasty Standard aspirin is as effective as the newer, direct oral anticoagulant (DOAC) rivaroxa- ban for preventing venous thromboembolism (VTE) in patients who have undergone total hip arthroplasty (THA) or total knee arthro- plasty (TKA), according to a report published in The New England Journal of Medicine. “DOACs are commonly prescribed for extended prophylaxis [as recommended in evidence-based guidelines] because of their effectiveness, safety, and convenience of use,” explained David R. Anderson, MD, of the Division of Hematology at the Dalhousie University in Nova Scotia, and co-authors. However, “aspirin, because of its efficacy, low cost, and well-established side-effect profile, [is] potentially a good choice for extended prophylaxis.” In the EPCAT II (Extended Venous Thromboembolism Prophylaxis Comparing Rivaroxaban to Aspirin Following Total Hip and Knee Arthroplasty II) trial, investigators compared the safety and efficacy of rivar- oxaban and aspirin after an initial five-day postoperative course of the DOAC. The double-blind, randomized, controlled trial enrolled 3,427 patients between January 2013 and April 2016 from 15 university-affiliated health centers in Canada. All patients were un- dergoing elective unilateral primary or revision THA or TKA. Patients were excluded if they had hip or lower limb fracture during the previous three months or metastatic cancer. Patients with long-term aspirin use at a dose of less than 100 mg per day could participate. The mean patient age was 62.8 years. Most patients (91.9%) underwent primary arthro- plasty procedures, and the average hospital stay was 3.5 days. All patients received in-hospital prophylaxis with oral rivaroxaban 10 mg once- daily for five days after surgery. Those undergoing TKA (n=1,620) were randomized to receive an additional nine days of thromboprophylaxis with either rivaroxaban 10 mg (n=815) or aspirin 81 mg (n=805); those undergoing THA (n=1,804) were randomized to receive an additional 30 days of rivaroxaban 10 mg (n=902) or aspirin 81 mg (n=902). At randomization, 855 people were receiv- ing long-term aspirin prophylaxis: 372 (20.6%) in the THA cohort and 483 (29.8%) in the TKA group. Three patients withdrew consent, so 3,424 people were included in the primary analysis: 1,717 in the rivaroxaban group and 1,707 in the aspirin group. During the 90-day follow-up, symptomatic VTE (defined as deep vein thrombosis [DVT] or pulmonary embolism [PE]; primary efficacy endpoint) occurred at similar rates in the aspirin- and rivaroxaban-treated patients (0.64% and 0.70%, respectively; see TABLE 1 ). Aspirin was non-inferior to rivaroxaban (p<0.001) but not superior (p=0.84) for the prevention of post- operative proximal DVT or PE. One death occurred in the aspirin group because of PE; the patient had undergone TKA, and the death occurred 31 days after randomization and 17 days after completion of aspirin prophylaxis. Major bleeding events (including major or clinically relevant non-major bleeding; primary safety endpoint) were reported by eight patients (0.47%) in the aspirin group and five patients (0.29%) in the rivaroxaban group (difference = 0.18 percentage points; 95% CI –0.65-0.29; p=0.42). Rates of the combined endpoint of major bleeding and clinically relevant non-major bleeding also were similar between the two cohorts: 22 patients (1.29%) in the aspirin-treated group and 17 (0.99%) in the rivaroxaban-treated group (difference = 0.30 percentage points; 95% CI –1.07-0.47; p=0.43). There were no significant differences in rates of thromboembolic events or bleeding complications in the THA or TKA subgroups treated with aspirin or rivaroxaban. Among the 855 patients who were receiving long-term aspirin therapy at randomization, rates of VTE, major bleeding, and clinically relevant non-major bleeding outcomes were similar to outcomes in the 2,569 patients who were not receiving such therapy (see TABLE 2 ). This finding “suggests that there was no benefit of adding aspirin 81 mg to either aspi- rin or rivaroxaban prophylaxis,” the researchers reported. “However, there were suggestions of more major and clinically relevant non-major bleeding among patients in the long-term as- pirin subgroup, particularly among those who had been assigned to the [aspirin] group and … were receiving a second daily dose of aspirin prophylaxis.” Patient recruitment frequently occurred TABLE 1. Primary Efficacy and Safety postoperatively, which the Outcome Rivaroxaban Aspirin p Value authors noted as a limitation (n=1,717) (n=1,707) of the study. In addition, VTE 12 (0.70%) 11 (0.64%) most bleeding events that PE 6 (0.35%) 5 (0.29%) were related to surgical-site 0.84 Proximal DVT 4 (0.23%) 4 (0.23%) bleeding occurred early after randomization, making it PE or proximal DVT 2 (0.12%) 2 (0.12%) difficult to determine whether Major bleeding 5 (0.29%) 8 (0.47%) 0.42 bleeding was predominantly Any bleeding 17 (0.99%) 22 (1.29%) 0.43 related to the initial course VTE = venous thromboembolism; PE = pulmonary embolism; DVT = deep vein thrombosis of postoperative rivaroxaban, trial medication (rivaroxaban vs. aspirin), or a combination TABLE 2. Subgroup Analysis of Primary Outcomes, According to Use of of both. Long-Term Aspirin Therapy The corresponding authors Outcome Long-Term Aspirin Therapy No Long-Term Aspirin Therapy report no financial conflicts. Rivaroxaban (n=429) Aspirin (n=426) p Value Rivaroxaban (n=1,288) Aspirin (n=1,281) p Value VTE 3 (0.70%) 3 (0.70%) 1.00 9 (0.70%) 8 (0.62%) 1.00 Major bleeding 1 (0.23%) 4 (0.94%) 0.22 4 (0.31%) 4 (0.31%) 1.00 Any bleeding 5 (1.17%) 8 (1.88%) 0.42 12 (0.93%) 14 (1.09%) 0.70 REFERENCE Anderson DR, J Murnaghan, SR Kahn, et al. Aspirin or rivaroxaban for VTE prophylaxis after hip or knee arthroplasty. N Engl J Med. 2018;378:699-707. VTE =