Treatment with sacubitril/valsartan in European outpatients with chronic heart failure in Europe: results from ARIADNE registry
Authors: Maggioni A , Barrios V , Clark A.L , Damy T , Drozdz J , Fonseca C , Lund L.H , Kalus S , Koch C , Zeymer U 
Published: November 2020

Abstract

Background
Recently, the angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan (S/V) was introduced as a novel therapeutic option into European guidelines for the management of heart failure (HF). The Assessment of Real lIfe cAre –Describing EuropeaN hEart failure management (ARIADNE) registry provides real world information about its use and efficacy in real life in outpatients with heart failure with reduced ejection fraction (HFrEF) in Europe.

Methods
ARIADNE was a prospective registry of patients with HFrEF (NYHA II-IV, reduced EF) treated by office-based cardiologists or selected primary care physicians (recognized as HF specialists) in a real world setting. 9069 HFrEF patients were enrolled from 674 investigators in 17 European countries, and followed over 12 months. Out of 8787 patients fulfilling criteria for analysis, 52.5% of the patients received S/V treatment at baseline, whereas 47.5% continued on their previous individualized heart failure medication. Results of S/V patients are reported here.

Results
The mean age of patients prescribed S/V was 67.3 years, mainly NYHA class II or III (49.7% and 48.2%, respectively), and mean LVEF of 32.7%. Common documented comorbidities were arterial hypertension (63.7%), coronary heart disease (62.4%), dyslipidemia (50.3%), diabetes (32.5%), and chronic kidney disease (24.1%).
Of the 4143 patients in the S/V group, 89.9% received S/V at baseline, 74.8% received S/V in combination with a β-blocker; 47.8% with a β-blocker and MRA.
Within 6 months of the observational period, 693 (17.4%) of the S/V patients were hospitalized, of which 46.8% and 28.7%, had HF related and non-HF cardiovascular (CV) hospitalizations. Emergency room visits without hospitalization were documented for 3.4% of S/V patients in the same time period; stroke and myocardial infarction occurred in 22 (0.5%) and 24 (0.6%) of the S/V patients, respectively. Cardiac catheterization or coronary angiography procedures were applied to 1.7% and 2.8% of the S/V patients. Total mortality was 4.3% (S/V 3.8%; non-S/V 5.0%), cardiovascular mortality 1.9% (S/V 1.8%; non-S/V 2.2%), during the 12 month observational period.
The proportion of S/V patients in NYHA class III or IV decreased in the course of the study from 44.6% to 24.0%. After 12 months of follow up, 46.3% of patients with NYHA class III had a reported improvement to NYHA class II. Consistently, mean LVEF increased to 37.9%. The percentage of S/V patients with LVEF &lt;22.5% decreased from 11.5% to 5.8%. KCCQ overall summary score increased by 1.9 points. An improvement of ≥5 points, denoting a clinically meaningful increase, was reported for 36.2% of S/V patients.

Conclusions
Data from the ARIADNE prospective registry portray a diverse, multinational study cohort receiving sacubitril/valsartan under real-world conditions. Throughout the study, symptoms and quality of life improved with the use of S/V.

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