Key result
Real-world HF patients receive ~42% lower sacubitril/valsartan doses than observed in PARADIGM-HF.
Why the study?
Does sacubitril/valsartan dosing and tolerability in real-world HFrEF patients differ from the PARADIGM-HF trial population?
Observational (n=120)
No
Does sacubitril/valsartan dosing and tolerability in real-world HFrEF patients differ from the PARADIGM-HF trial population?
Absolute Event Rate: 219% vs 375%
p-value: p=<0.001
Real-world HFrEF patients prescribed sacubitril/valsartan have more severe disease than trial populations, leading to lower achieved doses and greater blood pressure drops, though they still receive equipotent RAS inhibition.
Real-world HFrEF patients may tolerate lower sacubitril/valsartan doses; leaves open optimal dosing and outcome impact outside trials.
BACKGROUND: Sacubitril/valsartan significantly reduced heart failure hospitalization and mortality in PARADIGM-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With an Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure). However, real-world data from its use are lacking. METHODS AND RESULTS: We retrospectively assessed all baseline and follow-up data of consecutive heart failure patients with reduced ejection fraction receiving therapy with sacubitril/valsartan for Class I recommendation between December 2016 and July 2017. Baseline characteristics and dose titration of sacubitril/valsartan were compared between patients in clinical practice and in PARADIGM-HF. A total of 120 patients (81% male) were switched from angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to sacubitril/valsartan. A total of 20.1% of patients received dose uptitration. Patients were treated with an equipotential dose of renin-angiotensin system blockers before and after uptitration of sacubitril/valsartan (57 ± 29% vs. 53 ± 29% of target dose indicated by European Society of Cardiology guidelines; P = 0.286). However, they received a lower dose of sacubitril/valsartan in comparison with those in the PARADIGM-HF (219 ± 12 vs. 375 ± 75 mg; P < 0.001). In comparison with the patients receiving sacubitril/valsartan in PARADIGM-HF, patients in clinical practice were older and had a higher serum creatinine, higher New York Heart Association functional classification, and lower left ventricular ejection fraction (all P-value <0.05). Even in comparison with patients who experienced dropout during the run-in phase of PARADIGM-HF, real-world patients exhibited baseline characteristics indicative of more disease severity. Patients were at high absolute baseline risk for adverse outcome as illustrated by the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) risk score of 6 (inter-quartile range 3), in comparison with 5 (inter-quartile range 4) in PARADIGM-HF. After initiation of sacubitril/valsartan, New York Heart Association class significantly improved (P < 0.001), but systolic blood pressure dropped more than was reported in PARADIGM-HF (7.1 ± 8.0 vs. 3.2 ± 0.4 mmHg; P < 0.001). CONCLUSIONS: Patients in clinical practice exhibit baseline characteristics associated with more severe disease, which might lead to prescription of lower doses. Nevertheless, patients in clinical practice are at high risk of adverse outcome as illustrated by the EMPHASIS-HF risk score, underscoring the large potential for sacubitril/valsartan therapy to reduce the risk of heart failure hospitalization and all-cause mortality.
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Martens et al. (2018) conducted an observational in Heart failure with reduced ejection fraction (HFrEF) (n=120). Sacubitril/valsartan vs. PARADIGM-HF trial population was evaluated on Achieved dose of sacubitril/valsartan (p=<0.001). Real-world heart failure patients exhibited more severe baseline disease and received a significantly lower dose of sacubitril/valsartan compared to the PARADIGM-HF trial population (219 vs 375 mg).