Berberine HS events were more than halved in the dabigatran treated group. These differences in clinical event rates resulted in an increase in QALYs for dabigatran treated patients versus warfarin. This was accompanied by higher lifetime cost per patient for disease management with dabigatran, due to the higher drug costs. In both treatment groups, follow up costs represented the largest share of costs, with the remaining fraction attributed to acute event management. In the scenario analyses, aspirin and no treatment provided fewer QALYs than dabigatran. Aspirin resulted in lower overall costs than approved drug library dabigatran, but the higher event rate in the no treatment group resulted in higher total management costs, despite the absence of drug costs. Note that aspirin and no treatment were compared with dabigatran without a second line treatment. In the population initiating treatment atage 80 or above, total QALYs and costs were reduced. Costs had a similar breakdown of drug, acute event and follow up costs as the population initiating treatment before age 80.
In the population initiating treatment before age 80, the incremental research chemicals library cost effectiveness ratio was 831/QALY gained, while in the population initiating treatment at 80 the ICER was 090/QALY gained. In the scenario analyses which compared initiating dabigatran before age 80 with treatment with aspirin, the ICER was found to be 457/QALY gained, while dabigatran dominated receiving no thrombophylaxis. Deterministic sensitivity analyses Deterministic sensitivity analyses for the base case model showed cost effectiveness of dabigatran versus warfarin was robust to variations in the majority of parameters, including changes in underlying clinical event rates, costs, utilities and discounting. Key parameters that affected the cost effectiveness were the degree of INR control maraviroc attained by patients on warfarin, the RR and overall rates of IS, ICH and HS for dabigatran versus warfarin, the cost of long term follow up care for patients with disability, and time horizon analysed. Significant differences in the cost of INR monitoring while on warfarin also had an effect on the ICER.
To reach a willingness to pay threshold of 0 000 and 0 000/QALY gained required an average time in therapeutic range for the whole cohort of approximately 91% and 97% for the population starting therapy at age 80 years, and 80% and 83% in the population starting therapy at age $80 years, respectively. Over a time horizon of only 10 years, the mean survival of the modelled patient population, the ICER was 1 898/QALY gained. Using the upper limit of the 95% CI for the RR of IS, ICH or HS for dabigatran versus warfarin increased the ICERs to 3 353, 0 013 and 420/QALY gained, respectively. Using full RE LY clinical results instead of age stratified results yielded an ICER of 985/QALYand 3 645/QALY in the 80 and $80 populations, respectively. Probabilistic sensitivity analyses PSA simulation of dabigatran versus annum warfarin treatment for patients initiating treatment at age 80 or above showed that dabigatran increased QALYs in all simulation runs, with most, but not all, showing increased costs. Similarly, dabigatran resulted in an increase in QALYs in simulations versus aspirin or no treatment when patients initiated treatme.