Model parameters influencing the cost-effectiveness of sacubitril/valsartan in heart failure: evidence from a systematic literature review

Objectives To summarize cost-effectiveness (CE) evidence of sacubitril/valsartan for the treatment of heart failure (HF) patients with reduced ejection fraction (HFrEF). The impact of different modeling approaches and parameters on the CE results is also described. Methods We conducted a systematic literature review using multiple databases: Embase (R); MEDLINE (R); MEDLINE (R)-In Process; NIHR CRD database including DARE, NHS EED, and HTA databases; and the Cost Effectiveness Analysis registry. We also reviewed HTA countries' websites to identify CE reports of sacubitril/valsartan, published up to 25-July-2021. Articles published in English as full-texts, conference-abstracts, or HTA reports were included. Results We included 44 CE models [39 from 37 publications (22 full-texts; 15 conference-abstracts) and 5 HTAs; Europe, n = 20; North and South Americas, n = 14; Asia and Australia, n = 10]. Most models adopted a Markov structure with constant transition probabilities of events (n = 27) or a mix of Markov and regression-based models (n = 16), with variations in structural assumptions and chosen parameters. Study authors concluded sacubitril/valsartan to be a cost-effective therapy in 37/41 models in chronic HFrEF patients and 2/3 models in hospitalized patients stabilized after an acute decompensation for HF. CE models showing sacubitril/valsartan not to be a cost-effective treatment generally modeled a shorter time horizon. Effect of sacubitril/valsartan on cardiovascular and all-cause mortality, cost, duration of effect and time horizon was the main model drivers. Conclusions Most evidence indicated sacubitril/valsartan is cost-effective in HFrEF. The use of a lifetime horizon is recommended in future models as HF is a chronic disease. Data on the CE of sacubitril/valsartan in the inpatient setting were limited and further research is warranted.