A Mixed Treatment Comparison (Mtc) to Compare the Efficacy of Anti-Thrombotic Agents in the Acute Treatment of Venous Thromboembolism (Vte) in Patients with Active Cancer

Abstract

New oral anticoagulants (NOACs) are available for the treatment and prevention of VTE but evidence on their clinical effectiveness compared with existing treatments is limited. This research compared the clinical effectiveness of dabigatran, rivaroxaban, adjusted standard dose warfarin (warfarin), and low molecular weight heparin (LMWH) in people with active cancer following VTE. This research was conducted during a review of the company’s submission (CS) to the National Institute for Health and Care Excellence (NICE) Single Technology Appraisal programme for the oral direct thrombin inhibitor, dabigatran. Randomised controlled trials (RCTs) for inclusion were identified using the CS for dabigatran (as part of Technology Appraisal [TA]327), and two similar submissions for rivaroxaban (TA261 and TA287). RCTs were assessed for comparability based on patient population, disease severity, and treatments received. A Bayesian MTC was conducted, and fixed and random effects models were explored. Odds ratio (OR) was chosen as the summary statistic for VTE recurrence and major bleed. The network of 9 RCTs formed a “radiating star”. The fixed effects model had the lowest deviance information criterion (DIC) for VTE recurrence and major bleed and so was chosen as the best-fitting model. There was reasonable agreement between the number of unconstrained data points and the residual deviance for both outcomes. Results compared to dabigatran were (OR>1 favours dabigatran): VTE recurrence LMWH OR 0.96 (95% Credible Interval [95%CrI]: 0.15–3.37), rivaroxaban OR 1.29 (95%CrI: 0.12–5.42), warfarin OR 1.87 (95%CrI: 0.31–6.45); major bleed LMWH OR 0.85 (95%CrI: 0.15–2.67), warfarin OR 0.74 (95%CrI: 0.15–2.15). No data were available on major bleed for rivaroxaban in people with active cancer. There were no significant differences in the outcomes evaluated. However, the available evidence suggests that LMWH may have the lowest risk of VTE recurrence in the treatments assessed.