Age-based comparison of patients with heart failure treated with sacubitril-valsartan in France: a real-world evaluation

Abstract Background Sacubitril-Valsartan (S/V) was approved in Europe in 2015, for treatment of adults with symptomatic chronic heart failure with reduced left ventricular ejection fraction (HFrEF). In France, S/V had benefited from an early access program (2015-2018) and became available in community pharmacy since October 2018. Purpose Our study aimed to describe characteristics of patients who received S/V in France and to assess real-life mortality in this population regarding age. Methods This non-interventional retrospective study utilized existing claims data from the French National Healthcare Data System (SNDS) allowing long-term follow-up of patients who benefited from at least one reimbursement of S/V. Patient data between April 2012 and December 2020 were extracted from the database. Prespecified subgroup analyses were conducted for subjects aged <75 and ≥75 y to describe characteristics of patients at first reimbursement of S/V. Cardiovascular mortality and all-cause mortality were estimated using Kaplan-Meier method. Results Between 2015 and 2020, 104,910 patients initiated S/V and were followed for an average of 20 months; 42.6% (44,743 patients) were ≥75 y. Mean (SD) age difference between the 2 subgroups was 20.3 years [62.2 (9.6) vs 82.5 (5.2) in patients <75 and ≥75 y respectively]. Patients ≥75 y had a higher prevalence of atrial fibrillation (50.6% vs 31.2%) and chronic renal failure (20.9% vs 10.1%) and were less co-treated with mineralocorticoid-receptor antagonists (21.8% vs 40.5%) and ß-Blockers (64.0% vs 73.8%) compared to those <75 y. Three months after first dispensation, 48.3%, 35.3%, and 16.4% of patients aged ≥75 y received S/V dosages of 24/26mg, 49/51mg, and 97/103mg respectively, compared to 31.4%, 38.2%, and 30.4% for patients aged <75 y. The mean (SD) exposure period was 14.7 (13.6) months in patients ≥75 y vs 19.0 (15.5) months in <75 y patients. As expected, given the age difference, patients ≥75 y had a higher probability of all-cause mortality at 12-month 16.5% vs 6.2% in patients <75 y. Furthermore, 12-month cardiovascular mortality – evaluated during the early access program period (2015-2017) – in patients ≥75 y was 11.0% vs 4.8% in patients <75 y. Figures 1 and 2 show survival curves for cardiovascular mortality and all-cause mortality of these 2 subgroups. Of interest, cardiovascular mortality rate at 12 months was 7% in this study, compared to 6% in PARADIGM-HF, and all-cause mortality at 12-month was higher (10,6% vs 7%), likely due to the profile of the patients, who were older and have more comorbidities in real life. Finally, very few patients were hospitalized for reasons related to angioedema, 16/44,743 in ≥75 y patients and 26/60,167 in those <75 y. Conclusion This is the first French real-world study providing exhaustive nationwide data on S/V mortality over a period of almost 6 years in a very large population of elderly with a mean age of 70.9 y vs 63.8 y in PARADIGM-HF.Figure 1Figure 2