▪Introduction: Clinical trials have demonstrated that the new oral anticoagulants (NOACs), dabigatran, rivaroxaban, apixaban, and edoxaban are noninferior to standard therapies for treatment of acute symptomatic venous thromboembolism (VTE). We have previously published the medical costs avoided when NOACs are used instead of standard therapies based on rates of clinical events reported in clinical trials. However, the rates of recurrent VTE and major bleeding (MB) in the real-world settings may differ from those from the clinical trials. In this study, we estimated the real-world medical cost avoidance from a U.S. payer perspective when NOACs are used instead of standard therapy for the treatment of patients with VTE.Methods: Reduction of real-world event rates of recurrent VTE and MB were obtained by applying rate reductions observed in clinical studies to the Worcester population. Incremental annual medical costs among patients with VTE and MB from a U.S. payer perspective were obtained from the literature or healthcare claims databases and inflation adjusted to 2013 costs. Differences in total medical costs associated with clinical endpoints for patients treated with NOACs vs. standard therapy were then estimated. One-way univariate and Monte Carlo sensitivity analyses were additionally carried out. Univariate analysis varied the estimates of the clinical event rates between the ranges of confidence intervals and the estimates of event costs ±30% when such confidence intervals were not reported. Ten thousand cycles of Monte-Carlo simulations were used for additional sensitivity analysis where all model parameters were allowed to vary simultaneously.Results: Real-world event rates of recurrent VTE and MB in the Worcester VTE study were 11.2% and 10.8% respectively. Differences in real-world event rates of recurrent VTE among VTE patients treated with NOACs instead of standard therapy were estimated at -1.80% for apixaban, -1.23% for rivaroxaban, -2.02% for edoxaban, and 1.02% for dabigatran. Differences in real-world event rates of MB among VTE patients treated with NOACs instead of standard therapy were estimated at -7.48% for apixaban, -4.97% for rivaroxaban, -1.73% for edoxaban, and -2.57% for dabigatran. Based on the real-world data, the annual total medical cost avoidances vs. standard therapy were greatest for VTE patients treated with apixaban (-$4,440 per patient year-ppy), followed by those treated with rivaroxaban (-$2,971 ppy), edoxaban (-$1,957 ppy), and dabigatran (-$572 ppy). In comparison to data previously reported based on clinical trials, these medical cost avoidances are substantially greater for any of the NOACs vs. standard therapy (Table). The medical cost avoidances remained consistent under univariate (one-way) sensitivity. Additionally, the mean cost estimates of 10,000 random cycles of Monte-Carlo simulations for each of the NOACs were similar to the default estimated medical cost avoidances, demonstrating the robustness of the model estimates.Conclusions: Based on real-world data, when any of the evaluated NOACs are used instead of standard therapy for treatment of patients with acute VTE annual medical costs are reduced. In the real-world setting, the use of NOACs vs. standard therapy is predicted to be associated with even greater annual medical cost reductions than that previously estimated based on clinical trial data. Of the NOACs, apixaban has the greatest real-world medical cost avoidance, as its use is associated with substantial reductions in both VTE and MB event rates.Abstract 687. Table 1Estimates of Medical Cost Differences Among VTE Patients Treated with NOACs vs. Standard Therapy Based on Clinical Trial Data vs. Real-World DataOutcomeApixaban($/patient-yr)Rivaroxaban($/patient-yr)Edoxaban($/patient-yr)Dabigatran($/patient-yr)Recurrent VTE*Clinical trial data-$252-$132-$197$114Real-world data-$1,047-$717-$1,173$595Major bleedings*Clinical trial data-$572-$354-$109-$195Real-world data-$3,392-$2,254-$784-$1,167Total Medical Cost*Clinical trial data-$824-$486-$306-$80Real-world data-$4,440-$2,971-$1,957-$572*Negative values mean the NOAC is associated with lower total medical cost vs. standard therapy. DisclosuresAmin:Bristol-Myers Squibb, Pfizer: Consultancy. Off Label Use: Apixaban and edoxaban for the indication of VTE. Bruno:Bristol-Myers Squibb: Employment, Equity Ownership. Trocio:Pfizer: Employment, Equity Ownership. Lin:Bristol-Myers Squibb, Pfizer: Consultancy, Research Funding. Lingohr-Smith:Bristol-Myers Squibb, Pfizer: Consultancy, Research Funding.