Background:
Sacubitril/valsartan (Entresto
®
), available since 07/2015 to treat heart failure (HF) with reduced ejection fraction, reduced HF morbidity and mortality in the PARADIGM-HF trial at a mean daily dose of 375mg. The recommended starting dose is 49/51mg BID with up-titration to the target maintenance dose of 97/103mg BID. The uptake and pattern of dosage up-titration of sacubitril/valsartan in the real-world setting is understudied. Therefore, we characterize sacubitril/valsartan utilization patterns over time.
Methods:
We conducted a population-level cohort study using the IQVIA National Prescription Audit database from 08/2016-07/2019. Primary variables included the number of prescriptions (Rx) dispensed over a 3-year period and the proportion of Rx in the most recent 1-year period by dose, Rx types, prescriber and patient.
Results:
Over 3-years, 3.3 million sacubitril/valsartan Rx were dispensed. The number of Rx/month increased 5.6-fold, from 30,454 Rx to 175,605 Rx. Cardiologists prescribed 59% of Rx. However, non-cardiologists had a greater increase (7.5-fold) in prescribing over time than cardiologists (4.9-fold). During the most recent year, 49% of Rx were for the lowest dose of 24/26mg, followed by 31% for the intermediate 49/51mg dose, and 21% for the highest 97/103mg dose. There were more refill Rx than new Rx for all doses. For higher doses, more Rx were written by cardiologists than non-cardiologists (49/51mg: 59% vs. 41%; 97/103mg: 59% vs 41%, for cardiologists vs. non-cardiologists, respectively) (p<0.0001). There were fewer Rx for the target dose (97/103mg) in the oldest age than the youngest age category (11% for age 85+ vs. 24% for age 40-64 years).
Conclusions:
In the real-world setting, only 1 in 5 sacubitril/valsartan Rx dispensed in 2018/19 were for the target dose of 97/103mg with even lower use in the elderly population. The number of Rx prescribed by non-cardiologists has increased steeply, yet higher doses were prescribed more often by cardiologists. Given that these lower doses may not provide the same clinical benefits shown with higher doses in the PARADIGM-HF trial, identification of barriers or risk factors for underdosing of sacubitril/valsartan and its clinical implications warrants further evaluation.