Background: Based on the PARADIGM-HF trial, sacubitril/valsartan was approved for the treatment of patients with heart failure and reduced ejection fraction. This study provides an early view of its real-world utilization and dosing in the US before recent guideline updates.
Methods: Adult patients with >=1 sacubitril/valsartan claim in 7/7/2015 - 3/31/2016 were selected from a large national claims dataset; their 1st sacubitril/valsartan claim was the index date. Data was required for >=24 months pre-index and >=3 months post-index. Dose at index and the maximum dose achieved post-index were obtained. Dose up-titration, defined as 1st appearance of a sacubitril/valsartan claim with a dose increase from the index strength, and the time to 1st dose increase were reported.
Results: Among 981 qualified patients with a mean follow-up of 185 (SD ±81) days, 25% commenced sacubitril/valsartan on the suggested prescribing information (PI) starting dose of 49/51 mg b.i.d.; 58% started on 24/26 mg b.i.d.; 4% started on an even lower dose, and 13% indexed at the target maintenance dose of 97/103 b.i.d.. The target maintenance dose of 97/103 mg b.i.d. was achieved in 30% of patients. For those 856 patients indexing on <=49/51/ mg b.i.d., 58% had no dose up-titration post-index; 31% took >4 weeks to have up-titration initiated and 11% initiated up-titration within 4 weeks. Only 25% of Medicare patients compared to 35% of Commercial patients achieved the target dose of 97/103mg b.i.d.. (Table 1)
Conclusion: Most patients commenced sacubitril/valsartan at lower doses than recommended in the PI and were poorly optimized, with the majority of patients having no upward dose titration. Approximately 13% actually indexed at the target maintenance dose. The reasons for these findings need further exploration. Healthcare providers should consider following the appropriate starting doses, with timely dose adjustment of sacubitril/valsartan as recommended in the PI to ensure patients receive the full clinical benefit of this medication as demonstrated in the PARADIGM-HF trial.