Patient and clinical characteristics of heart failure patients concomitantly prescribed SGLT2 inhibitors and sacubitril/valsartan, a database cohort study using the Optum electronic health record data
Authors: Loefroth E , Hughes M , Shi Y , Wang Y , Proudfoot C , Di Domenico M , Modgill V , Schlienger R , Studer R 
Published: November 2020

Abstract

Background and purpose
Sacubitril/valsartan (sac/val), an angiotensin receptor neprilysin inhibitor, reduces the risk for cardiovascular (CV) death or hospitalization for heart failure (HF) in HF with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are approved in patients with type 2 diabetes (T2D) and have shown to reduce the CV risk in T2D patients with established CV or at risk of CV disease. The SGLT2i dapagliflozin has shown to improve outcomes in patients with chronic HFrEF, with or without T2D, when used in addition to standard of care including sac/val. As the use of SGLT2i in HF evolves, and given the large overlap of HF and T2D populations, it is of interest to understand the population with concomitant use of sac/val and SGLT2i. This study describes the clinical characteristics of patients treated concomitantly with sac/val and SGLT2i or concomitantly with sac/val and dipeptidyl peptidase-4 inhibitors (DPP4i) or glucagon-like peptide-1 receptor agonists (GLP1), two comparable second line anti-diabetic drug classes.

Methods
This retrospective non-interventional study describes two mutually exclusive adult patient cohorts diagnosed with HF and T2D concomitantly prescribed sac/val and SGLT2i (cohort 1), or concomitantly prescribed sac/val and DDP4i/GLP1 (cohort 2). The index date was defined as the first date of concomitant use with prescriptions overlapping a minimum of 21 days. Patients were identified any time between 1/1/2015 and 30/6/2019 in the Optum® de-identified electronic health record (EHR) data from providers across the continuum of care.

Results
2.3 million HF patients were identified, and 41.6% had a T2D diagnosis. 560 patients were concomitantly prescribed sac/val and SGLT2i (cohort 1) and 1,566 concomitantly sac/val and DDP4/GLP1 (cohort 2). There was a higher proportion of females in cohort 2 (35.0% vs 27.9%). Mean age was higher in cohort 2 (66.4 vs 61.4 years). The mean estimated glomerular filtration rate was 85.93 (SD 23.43) ml/min/1.73m2 (cohort 1) and 72.10 (Std. 27.11) ml/min/1.73m2 (cohort 2). The proportion of stage 3 CKD (&lt;60 to &gt;30 ml/min/1.73m2) was 11.8% (cohort 1) and 24.4% (cohort 2). Mean systolic blood pressure was similar, 120 mmHg (cohort 1) and 122 mmHg (cohort 2). Mean hemoglobin was 13.60 g/dl (cohort 1) and 12.43 g/dl (cohort 2). Median (IQR) NT-proBNP differed between the two cohorts, 914 (2154) pg/ml (cohort 1) and 2,290 (5,301) pg/ml (cohort 2) but with complete values available in only 17.7 and 19.0% of each cohort.

Conclusions
This descriptive analysis of concomitant prescription of sac/val and SGLT2i or DPP4/GLP1 highlights differences in the clinical characteristics between the two cohorts. The patients treated with sac/val and SGLT2i start with a more favorable clinical profile compared to the patients treated with sac/val and DPP4/GLP1. Further analyses are needed to determine if these differences are driven by age, gender or other factors.

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): Novartis Pharma AG