Key result
Sacubitril/valsartan up-titration to higher doses was achieved in 57 of 201 (28.4%) HFrEF patients, with success associated with younger age, higher hemoglobin, and better renal function.
Why the study?
Practice guidelines recommend sacubitril/valsartan for HFrEF, but real-world data were needed to identify patients best able to tolerate titration to higher doses.
What clinical characteristics predict the ability to tolerate up-titration of sacubitril/valsartan in a real-world HFrEF population?
Cohort (n=201)
No
What clinical characteristics predict the ability to tolerate up-titration of sacubitril/valsartan in a real-world HFrEF population?
In a real-world HFrEF population, over one-third of patients tolerated higher doses of sacubitril/valsartan, with successful up-titration predicted by younger age, better renal function, higher hemoglobin, and higher blood pressure.
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.
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Mapelli et al. (2020) conducted a cohort in Heart failure with reduced ejection fraction (HFrEF) (n=201). Sacubitril/valsartan vs. Discontinuation or death was evaluated on Tolerability of titration to higher doses of sacubitril/valsartan. Sacubitril/valsartan up-titration to higher doses was achieved in 57 of 201 (28.4%) HFrEF patients, with success associated with younger age, higher hemoglobin, and better renal function.
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