Rivaroxaban versus nadroparin for thromboprophylaxis following thoracic surgery for lung cancer: A randomized, noninferiority trial

Abstract

The benefit of rivaroxaban in thromboprophylaxis after oncologic lung surgery remains unknown. To evaluate the efficacy and safety of rivaroxaban, patients who underwent thoracic surgery for lung cancer were enrolled, and randomly assigned to rivaroxaban or nadroparin groups in a 1:1 ratio; anticoagulants were initiated 12–24 h after surgery and continued until discharge. Four hundred participants were required according to a noninferiority margin of 2%, assuming venous thromboembolism (VTE) occurrence rates of 6.0% and 12.6% for patients in the rivaroxaban and nadroparin groups, respectively. The primary efficacy outcome was any VTE during the treatment and 30‐day follow‐up periods. The safety outcome was any on‐treatment bleeding event. Finally, 403 patients were randomized (intention‐to‐treat [ITT] population), with 381 included in per‐protocol (PP) population. The primary efficacy outcomes occurred in 12.5% (25/200) of the rivaroxaban group and 17.7% (36/203) of the nadroparin group (absolute risk reduction, −5.2%; 95% confidence interval [CI], [−12.2–1.7]), indicating the noninferiority of rivaroxaban in ITT population. Sensitivity analysis was performed in the PP population and yielded similar results, confirming the noninferiority of rivaroxaban. In the safety analysis population, the incidence of any on‐treatment bleeding events did not differ significantly between the groups (12.2% for rivaroxaban vs. 7.0% for nadroparin; relative risk [RR], 1.9; 95% CI, [0.9–3.7]; p = .08), including major bleeding (9.7% vs. 6.5%; RR, 1.6 [95% CI, 0.9–3.7]; p = .24), and nonmajor bleeding (2.6% vs. 0.5%; RR, 5.2 [95% CI, 0.6–45.2]; p = .13). Rivaroxaban for thromboprophylaxis after oncologic lung surgery was shown to be noninferior to nadroparin.

Efficacy and safety of direct oral anticoagulants versus low-molecular-weight heparin for thromboprophylaxis after cancer surgery: a systematic review and meta-analysis

“…A total of 10 studies (three RCTs [ 21 , 22 , 32 ] and 7observational studies [ 33 – 39 ]), encompassing 3054patients, were included in the systematic review. Of the 10 studies, eight (three RCTs [ 21 , 22 , 32 ] and five observational studies [ 34 , 36 – 39 ]) were included in the pooled analysis comparing the efficacy and safety of thromboprophylaxis after cancer surgery within 30 days. The types of cancer included gynecological malignancies ( n = 5), urological malignancies ( n = 3), Pancreatic adenocarcinoma ( n = 1) and lung cancer ( n = 1).…”

“…Two of the three randomized controlled trials were adjudicated to a low risk of bias [ 21 , 32 ] and one had some concern because the trial was stopped due to a lower-than-expected event rate [ 22 ] (Fig. 2 A).…”

“…Of the 10 studies, 30-day clinical VTE was assessed in 8 studies (3 RCTs [ 21 , 22 , 32 ] and 5 observational studies [ 34 , 36 – 39 ]). We pooled the outcome by 30 days postoperative comparisons between DOAC and LMWH.…”

“…3 A). Meanwhile, we also pooled the data from 4 studies (1 RCT [ 20 ] and 3 observational studies [ 32 , 33 , 37 ]) and showed no significant difference between both groups for postoperative VTE within 90 days (Supplementary Fig. 1 A).…”

In-hospital thromboprophylaxis variation and the risk of venous thromboembolism after lung cancer surgery: a nationwide cohort study

“…However, prophylactic anticoagulation also has drawbacks, including increased risk of bleeding, costs, patient discomfort and inconvenience. Oral alternatives such as direct-acting oral anticoagulants (DOACs) obviate the need for daily injections with documented comparable efficacy to LMWH [ 19 , 20 ]. This calls for a need to personalize decision-making about thromboprophylaxis and consider extended prophylaxis for high-risk patients such as those with large resections, advanced cancer stage, central tumours compressing veins or undergoing treatment with systemic therapies (e.g.…”