Safety and Efficacy of Apixaban vs Enoxaparin for Preventing Postoperative Venous Thromboembolism in Women Undergoing Surgery for Gynecologic Malignant Neoplasm

Abstract

IMPORTANCE Current guidelines recommend a 28-day course of enoxaparin for thromboprophylaxis after surgery for gynecologic cancer. The high cost of this medication and the low adherence rates observed in prior studies provide an opportunity to benefit patients by demonstrating the safety of a more cost-effective, easier to use thromboprophylactic. OBJECTIVE To investigate the safety and efficacy of an oral treatment alternative for thromboprophylaxis in postoperative patients with gynecologic cancer. DESIGN, SETTING, AND PARTICIPANTS This was a patient-based, multicenter, open-label, blinded, end point, randomized clinical trial conducted May 2015 to March 2019 in outpatient and inpatient gynecologic oncology settings. Women undergoing surgery for suspected or confirmed gynecologic cancer were approached for recruitment. The trial compared rates of major bleeding and clinically relevant nonmajor bleeding events during a 90-day follow-up period in patients taking apixaban or enoxaparin for postoperative thromboprophylaxis using a modified intent-to-treat analysis. Data analysis was performed from October to December 2019. INTERVENTIONS Women were randomized to 28 days of apixaban (2.5 mg orally twice daily) or enoxaparin (40 mg subcutaneously daily). MAIN OUTCOMES AND MEASURES The primary outcome was major bleeding and clinically relevant nonmajor bleeding events. Secondary outcomes included incidence of venous thromboembolic events, adverse events, medication adherence, participant quality of life, and medication satisfaction. RESULTS Of 500 women recruited for the study, 400 were enrolled and randomized (median age, 58.0 years; range, 18.0-89.0 years); 204 received apixaban and 196 received enoxaparin. Treatment groups did not differ in terms of race/ethnicity, cancer stage, or surgery modality (open vs robotic). There were no statistically significant differences between the apixaban and enoxaparin groups in terms of rates of major bleeding events (1 patient [0.5%] vs 1 patient [0.5%]; odds ratio [OR], 1.04; 95% CI, 0.07-16.76; P > .99), clinically relevant nonmajor bleeding events (12 patients [5.4%] vs 19 patients [9.7%]; OR, 1.88; 95% CI, 0.87-4.1; P = .11), venous thromboembolic events (2 patients [1.0%] vs 3 patients [1.5%]; OR, 1.57; 95% CI, 0.26-9.50; P = .68), adverse events, medication adherence, or quality of life between the groups. Participant satisfaction was significantly greater in the apixaban group with regard to ease of taking the medication (186 patients [98.9%] vs 110 (continued) Key Points Question Is there an efficacious and safe oral treatment for thromboprophylaxis in postoperative patients with suspected gynecologic malignant neoplasms? Findings This multicenter randomized clinical trial included 400 women randomized to either oral apixaban or subcutaneous enoxaparin. There were no differences between groups for rates of major bleeding (0.5% vs 0.5%), clinically relevant nonmajor bleeding (5.4% vs 9.7%), and venous thromboembolic events (1.0% vs 1.5%); although adherence rates did not d...

Enhanced Recovery and Surgical Optimization Protocol for Minimally Invasive Gynecologic Surgery: An AAGL White Paper

“…Enoxaparin 40 mg SC daily is most commonly prescribed for extended VTE pharmacoprophylaxis. However, there are emerging data that the direct oral anticoagulant apixaban is a potentially safe alternative [153].…”

Use of direct oral anticoagulants for postoperative venous thromboembolism prophylaxis after surgery for gynecologic malignancies

“…The authors found no significant difference between the groups in terms of major bleeding events, with only one event in each group (OR 1.04, 95% CI 0.07 to 16.76). 19 There was also no difference in clinically relevant non-major bleeding events, such as hematoma, bruising, vaginal bleeding, or epistaxis (OR 1.88, 95% CI 0.87 to 4.1). Additionally, to assess efficacy, there was no difference in venous thromboembolism events between groups: 1% in the apixaban arm and 1.5% in the low molecular weight heparin arm (OR 0.63, 95% CI 0.12 to 3.75).…”

“…At present, there is only one completed randomized controlled trial assessing the use of direct oral anticoagulants in patients following surgery for gynecologic malignancy. Guntupalli et al enrolled 400 women with suspected or known gynecologic malignancies undergoing surgery 19 (online supplemental Table 1). Approximately half of their study population were randomized to 2.5 mg of oral apixaban twice a day and other half to 40 mg subcutaneous low molecular weight heparin (enoxaparin).…”

“…Approximately half of their study population were randomized to 2.5 mg of oral apixaban twice a day and other half to 40 mg subcutaneous low molecular weight heparin (enoxaparin). 19 Both medications were administered for 28 days. The primary outcome assessed the safety of apixaban prophylaxis compared with low molecular weight heparin.…”

Apixaban vs Enoxaparin for Postoperative Prophylaxis: Safety of an Oral Alternative for the Prevention of Venous Thromboembolism

“…Dr Guntupalli and colleagues addressed these questions in this 2-site randomized clinical trial of apixaban vs enoxaparin prophylaxis in a postoperative gynecologic oncology population. 6 This trial enrolled 400 women undergoing surgery for known or suspected gynecologic malignancies. Once deemed stable following surgery, each patient was randomized 1:1 to either apixaban 2.5 mg orally twice a day or enoxaparin 40 mg subcutaneously daily for 28 days.…”