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Abstract 4209 Background: The risk of recurrent venous thromboembolism (VTE) in patients with cancer-associated VTE, remains high even with the use of low molecular weight heparin (LMWH). However, due to the heterogeneity of the disease it is probable that recurrence risk varies widely. We have developed a prediction rule to classify risk of recurrence in the first 6 months of treatment: + 1 is scored for each of female gender, lung cancer and prior VTE and – 1 is scored for breast cancer and – 2 for TNM stage 1 disease. With a score of ≤ 0, 4.5% of patients recur (this represented 48% of the patient populations), and > 0, 19.7% recur. The rule was derived in a retrospective cohort study of patients followed at the Thrombosis unit of the Ottawa hospital and requires validation. Methods: We applied our rule in a new set of 819 consecutive patients with cancer-associated VTE from 2 multicentre randomized controlled trials comparing LMWH with vitamin K antagonists (VKA) (ClotCant group). In these studies the stage of disease was not separated by exact TNM classification, rather patients were classified as stage I, II (no metastasis) versus III, IV (metastasis). As such, we redid our derivation model with stage I and II grouped together, which gave this variable a score of – 1. This resulted in a prediction rule which gave a recurrence risk that no longer clearly dichotomized risk; rather gave a low, intermediate, and high risk groups. As in our derivation study, we evaluated patients' risk of recurrence regardless of type of anticoagulant use (VKA or LMWH). Results: Of 819 patients, 86 (10.5%) presented with a VTE recurrence during the anticoagulation period. When we applied our derivation rule in this population, we were able to demonstrate a significant difference in VTE recurrence risk dependent on gender, primary tumour site, stage and history of prior VTE. Patients with a score < 0 have low risk (5.1%) for VTE recurrence and this represented 19% of the patient population; patients with a score of 0 had a intermediate risk (9.8%) and this represented 42% of patients; a score ≥ 1 was high risk (13.9%), occurring in 38% of the population. Dichotomizing the results gave a recurrence risk of 8% in patients with a score ≤ 0 and a 15.2% recurrence risk with a score > 0. Conclusion: the validation dataset suggests reproducibility of our model. The dichotomized score is less discriminatory than our original model suggesting an advantage to classifying patients tumour stage as TNM stage I versus stage II, III and IV. Unfortunately, we could not test this hypothesis with the ClotCant dataset. Our model appears to differentiate risk for recurrence and should be utilized in treatment trials: attempting novel treatment strategies in high risk patients since LMWH alone does not seem to be enough; and using the less costly typical “LMWH followed by oral anticoagulants” in the low risk population to evaluate whether VKA can be as safe and effective as long term LMWH. Disclosures: Lee: Eisai: Research Funding; Sanofi Aventis: Consultancy, Honoraria; Leo Pharma: Consultancy; Pfizer: Consultancy, Honoraria; Bayer: Honoraria; Boehringer Ingelheim: Consultancy, Honoraria, Speakers Bureau.

Introduction: Rivaroxaban is a novel, oral, direct Factor Xa inhibitor under regulatory review for the prevention of venous thromboembolism (VTE) after major orthopaedic surgery. Two large, randomized controlled trials compared 10 mg rivaroxaban once daily (od) with subcutaneous (sc) enoxaparin 40 mg od (RECORD3) and enoxaparin 30 mg twice daily (bid)(RECORD4) in patients undergoing total knee replacement (TKR). Rivaroxaban and enoxaparin were administered for 12 ± 2 days in both trials. In RECORD3, rivaroxaban was associated with a relative risk reduction (RRR) of 49% in total VTE (composite of any deep vein thrombosis, non-fatal pulmonary embolism and all-cause mortality) and 66% in symptomatic VTE versus enoxaparin (p=0.005). In RECORD4, rivaroxaban reduced total VTE versus enoxaparin (RRR 32%, p=0.012). There was no statistical difference in major bleeding between rivaroxaban and enoxaparin in either study. Although the comparison between rivaroxaban and enoxaparin is important, there are alternative VTE prophylaxes such as warfarin, fondaparinux and dabigatran (which received EU marketing approval in March 2008) for which there are no direct comparisons with rivaroxaban. This analysis was designed to assess the relative efficacy and safety of rivaroxaban versus warfarin, fondaparinux and dabigatran. This is important for clinical decision makers, but also provides important inputs for cost-effectiveness analyses of rivaroxaban versus these comparators. Methods: The efficacy of rivaroxaban relative to warfarin, fondaparinux and dabigatran was assessed by comparing the occurrence of total VTE, total DVT (proximal and distal) and symptomatic DVT. Relative safety was assessed using rates of major bleeding. A systematic literature review identified randomised control trials (RCTs) comparing enoxaparin to warfarin, fondaparinux or dabigatran in TKR. Each of these publications was reviewed by independent analysts. Data for relevant efficacy and safety outcomes were taken from these studies, and from RECORD3 and 4 for rivaroxaban versus enoxaparin. If more than one set of RCTs were available for each comparator, a meta-analysis was undertaken to obtain the pooled results for efficacy and safety (Bucher et al., 1997). Indirect comparisons were conducted based on the summary statistics obtained in each meta-analysis. Results are presented for the indirect comparisons through enoxaparin 30 mg bid and enoxaparin 40 mg od separately. The results from such an analysis do not represent the same level of evidence as a comparative trial, but they provide a guide to potential relative efficacy and safety in the absence of a comparative trial and could be used by authorities to aid decision making (NICE, 2007). Results: Rivaroxaban significantly reduced the incidence of key outcomes. When enoxaparin 30 mg bid was used as the common comparator, rivaroxaban was associated with reductions in total VTE of 56% versus warfarin (p Conclusions: An indirect statistical comparison showed that rivaroxaban reduced the incidence of overall or symptomatic VTE events relative to alternative prophylaxes without increasing major bleeding following TKR. In the absence of direct comparisons, this is the best evidence regarding the relative efficacy and safety of these options.