Sacubitril/valsartan use in a real-world population of patients with heart failure and reduced ejection fraction

Abstract

Aims Practice guidelines recommend sacubitril/valsartan for heart failure with reduced ejection fraction. The aim of our study was to describe the use of sacubitril/valsartan in real-world clinical practice to help identify patients best able to tolerate titration to higher doses. Methods We retrospectively analyzed clinical data for 201 patients with heart failure with reduced ejection fraction prescribed sacubitril/valsartan at our heart failure clinic (Centro Cardiologico Monzino) between September 2016/December 2018. Patients had a mean age of 67.2 years, mean left ventricular ejection fraction of 30.1%, New York Heart Association class II (65%), class III (35%), and poor cardiopulmonary exercise capacity. Median 2-year risk of death/urgent cardiac transplantation was 8.9% [Metabolic Exercise Cardiac Kidney Index (MECKI) score]. Results After a median follow-up of 230 (interquartile interval: 105–366) days, 57 patients achieved higher-dose sacubitril/valsartan, 103 tolerated medium/low doses, nine died, and 20 interrupted treatment. The highest dose of sacubitril/valsartan was reached by younger patients with better hemoglobin (Hb) levels, renal function, and blood pressure (BP). Patients continuing on sacubitril/valsartan had significantly higher serum Hb and sodium, better BP, and lower MECKI scores than patients who discontinued treatment or died during follow-up. Our patients were older and frailer than those in the pivotal PARADIGM-HF trial. Conclusion In our experience, more than one-third of the patients were able to tolerate the higher dose of sacubitril/valsartan, and these patients were younger, had higher Hb, and better BP and renal function. MECKI score stratification was useful to discriminate patients who continued treatment from those who did not. Future prospective studies should test if these clinical variables can guide the up-titration of sacubitril/valsartan.

Sacubitril/valsartan in real‐life European patients with heart failure and reduced ejection fraction: a systematic review and meta‐analysis

“…Twenty‐one articles, 10 retrospective and 11 prospective, were selected 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 (Supporting Information, Figure S1 and Tables S2 and S3 ). Collectively, these studies included 16 952 patients: 12 082 (71.3%) were accounted for by a single article, 16 while the sample size of the other ones varied from 11 (0.06%) to 2037 (12.0%) subjects.…”

“…Collectively, these studies included 16 952 patients: 12 082 (71.3%) were accounted for by a single article, 16 while the sample size of the other ones varied from 11 (0.06%) to 2037 (12.0%) subjects. 11 , 12 , 13 , 14 , 15 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 Four investigations included patients in NYHA class I (Lopez‐Azor 23 : 1.1%; Vicent 18 : 1.2%; Kakuzna 11 : 3.0%; and Pharithi 24 : 10.4%).…”

“…Ten (47.6%) of the selected articles were from Italy. Of these, only one described more than 100 subjects, 31 and it was also characterized by a relatively low proportion of missing variables; KC was 1.8%. The other nine studies from Italy yielded a KC < 1% each ( Table 2 ).…”

Hyponatraemia in heart failure: time for new solutions?

“…In the Comparison of Sacubitril/Valsartan Versus Enalapril on Effect on NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode (PIONEER-HF) study of acute HFrEF, a single case of hyponatraemia was reported in the enalapril group, which was not observed with sacubitril/valsartan 28. Two cases of sacubitril/valsartan-induced hyponatraemia were described29 30; however, observational studies show either no significant long-term changes or even some increase in serum sodium with sacubitril/valsartan, suggesting that it might prevent rather than trigger hyponatraemia 31–33…”

Future developments in the MECKI score initiative

“…The MECKI score has been shown to be able to differentiate between HFrEF patients able, or not able, to tolerate high dose sacubitril/valsartan dosing long term. 9 This may well be true of other risk scores for HFrEF, as it is plausible they can all predict sickest, highest risk patients, because of advanced age, low blood pressure or poor renal function, or the presence and severity of other co-morbidities. Nonetheless it is an important finding for it shows the potential of the MECKI score to be used in routine practice in aiding clinical decision making, predicting which patients will likely tolerate certain drug therapies.…”