Rivaroxaban Versus Enoxaparin for Thromboprophylaxis After major Gynecological Cancer Surgery: The VALERIA Trial

Abstract

Direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) prevention after major gynecological cancer surgery might be an alternative to parenteral low-molecular-weight heparin (LMWH). Patients undergoing major gynecological cancer surgery were randomized at hospital discharge to receive rivaroxaban 10 mg once daily or enoxaparin 40 mg once daily for 30 days. The primary efficacy outcome was a combination of symptomatic VTE and VTE-related death or asymptomatic VTE at day 30. The primary safety outcome was the incidence of major or clinically relevant nonmajor bleeding. Two hundred and twenty-eight patients were enrolled and randomly assigned to receive rivaroxaban (n = 114)or enoxaparin (n = 114). The trial was stopped due to a lower-than-expected event rate. The primary efficacy outcome occurred in 3.51% of patients assigned to rivaroxaban and in 4.39% of patients assigned to enoxaparin (relative risk 0.80, 95% CI 0.22 to 2.90; p = 0.7344). Patients assigned to rivaroxaban had no primary bleeding event, and 3 patients (2.63%) in the enoxaparin group had a major or CRNM bleeding event (hazard ratio, 0.14; 95% CI, 0.007 to 2.73; P = 0.1963). In patients undergoing major gynecological cancer surgery, thromboprophylaxis with rivaroxaban 10 mg daily for 30 days had similar rates of thrombotic and bleeding events compared to parenteral enoxaparin 40 mg daily. While the power is limited due to not reaching the intended sample size, our results support the hypothesis that DOACs might be an attractive alternative strategy to LMWH to prevent VTE in this high-risk population.

Comparison of the Efficacy and Safety of Rivaroxaban and Low Molecular Heparin in Preventing Venous Thromboembolism in Inpatient Cancer Patients

“…Our study is essentially similar to Longo de Oliveira et al 26 Oliveira et al found no significant difference between rivaroxaban and LMWH in preventing postoperative VTE and bleeding (either major or minor) in patients with gynecologic oncology cancer. However, in this study, minor bleeding was higher in both groups than in the study by Oliveira et al It was higher in the rivaroxaban group than in the LMWH group.…”

Preoperative Venous Thromboembolism Screening and Postoperative Selective Anticoagulant Therapy Effectively Prevents Postoperative Symptomatic Venous Thromboembolism in Gynecological Malignancies: A 15-Year, Single-Center Study

“…The VALERIA study, another recent prospective, randomized trial comparing 30-day rivaroxaban versus enoxaparin in VTE prophylaxis after major gynecological cancer surgery, reported that symptomatic VTE was 2.63% versus 1.75% (relative risk, 1.50; 95% CI, 0.25–8.80; P = .6535) and major/clinically relevant nonmajor bleeding was 0% versus 2.63% (hazard ratio, 0.14; 95% CI, 0.007–2.73; P = .1963). 23 The authors concluded that their results support the hypothesis that DOACs might be an attractive alternative strategy to LMWH to prevent VTE after major gynecological cancer surgery. As regards the current study, the incidence of postoperative symptomatic VTE was 0.6% in Period 2 and 0.3% in Period 3 ( Table 3 ), both of which were lower than those by LMWH and DOAC in the two trials.…”

“…As regards the current study, the incidence of postoperative symptomatic VTE was 0.6% in Period 2 and 0.3% in Period 3 ( Table 3 ), both of which were lower than those by LMWH and DOAC in the two trials. 21 , 23 Although the prophylactic effect of the measures in Period 1 is undetermined due to the absence of publications on the postoperative symptomatic VTE incidences without prophylaxis, it is possible that our preoperative VTE screening contributes to effective prevention of postoperative symptomatic VTE in all the study periods. Furthermore, none of the patients with preoperative VTE who switched to DOAC in Period 3 developed symptomatic VTE with no increase in Grade ≥3 postoperative hemorrhage ( Table 3 ).…”

Advances and current research in primary thromboprophylaxis to prevent hospital‐associated venous thromboembolism

“…32 A further study has since terminated early (due to lower than anticipated event rates), demonstrating similar VTE and bleeding rates in women receiving rivaroxaban 10 mg daily compared to enoxaparin 40 mg daily for 30 days from hospital discharge following gynaecological cancer surgery. 71…”

“…These studies drove the recent recommendation from the American Society of Clinical Oncology to include rivaroxaban and apixaban as an option for extended thromboprophylaxis following cancer surgery, with a caveat that the level of evidence remains low due to variation in timing of DOAC initiation, duration of initial heparin lead‐in, and in both type of cancer, and surgery performed 32 . A further study has since terminated early (due to lower than anticipated event rates), demonstrating similar VTE and bleeding rates in women receiving rivaroxaban 10 mg daily compared to enoxaparin 40 mg daily for 30 days from hospital discharge following gynaecological cancer surgery 71 …”