Cost-effectiveness analysis of apixaban versus other NOACs for the prevention of stroke in Italian atrial fibrillation patients

OBJECTIVES: The study evaluated the cost-effectiveness of apixaban in preventing thromboembolic events in nonvalvu-lar atrial fibrillation (NVAF) patients, as compared to other three available novel oral anticoagulant agents (NOACs), from the Italian Health System (SSN) perspective. METHODS: A previously published lifetime Markov model was adapted for the Italian context. Baseline clinical risks were assigned based on the demographic and clinical features of the patients; effectiveness and safety parameters derived from adjusted indirect comparison using warfarin as link. The main clinical events considered in the model are ischemic and hemorrhagic stroke, systemic thromboembolism, bleeds (both major and clinically relevant minor) and cardiovascular hospitalizations, besides treatment discontinuations. Expected survival was projected beyond trial duration using national mortality data adjusted for clinical risks and weighted by published utilities. Unit costs were collected from published Italian sources and actualized to 2013. Costs and health gains occurring after the first year were discounted at an annual 3.5% rate. The primary outcome measure of the economic evaluation was the incremental cost effectiveness ratio (ICER), where effectiveness is measured in terms of life-years and quality adjusted life-years gained. Deterministic and probabilistic sensitivity analyses (DSA& PSA) were carried out. RESULTS: In the short to medium term, apixaban was associated with marginal LYs and QALYs gains and slight savings, as compared to other NOACs. However, as apixaban extended expected survival versus dabigatran (110mg), dabigatran (150mg) and rivaroxaban (0.13, 0.08, and 0.06 LYs or 0.11, 0.07, and 0.05 QALYs), expected total lifetime costs exceeded those of these comparators ((sic) 319, (sic) 282, and (sic) 16). Corresponding ICERs were estimated in (sic) 2,911, (sic) 3,882 and (sic) 327 per QALY gained. The most influential parameter according to DSA was daily costs of NOACs, but the corresponding ICERs remained well below commonly accepted WTP values. In PSA, the probabilities of apixaban being cost effective with a WTP threshold of 20,000 (sic)/QALY gained were 99%, 92% and 93% for the same comparisons. CONCLUSIONS: Apixaban is expected to be more effective than dabigatran and rivaroxaban in Italian NVAF population, and marginally more costly due to consume healthcare resources for a longer period of time. The ICERs have a high likelihood of being below conventional thresholds of WTP for health benefits of the SSN and suggest that apixaban is cost-effective compared with other three available NOACs.