2019
DOI: 10.1056/nejmoa1908655
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Abstract: The angiotensin receptor-neprilysin inhibitor sacubitril-valsartan led to a reduced risk of hospitalization for heart failure or death from cardiovascular causes among patients with heart failure and reduced ejection fraction. The effect of angiotensin receptor-neprilysin inhibition in patients with heart failure with preserved ejection fraction is unclear. METHODS We randomly assigned 4822 patients with New York Heart Association (NYHA) class II to IV heart failure, ejection fraction of 45% or higher, elevate… Show more

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Cited by 1,521 publications
(1,366 citation statements)
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References 24 publications
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“…Although these haemodynamic assessments are likely to be fruitful in patients with a metabolic disorder and dyspnoea or AF, it is difficult to recommend the widespread use of invasive measurements to confirm the diagnosis of HFpEF, given the paucity of established treatments for the disorder. Furthermore, the results of the PARAGON‐HF trial with sacubitril–valsartan highlight the heterogeneity of the disease; the effects of neprilysin inhibition in patients in the trial with obesity or type 2 diabetes have not yet been presented.…”
Section: Discussionmentioning
confidence: 99%
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“…Although these haemodynamic assessments are likely to be fruitful in patients with a metabolic disorder and dyspnoea or AF, it is difficult to recommend the widespread use of invasive measurements to confirm the diagnosis of HFpEF, given the paucity of established treatments for the disorder. Furthermore, the results of the PARAGON‐HF trial with sacubitril–valsartan highlight the heterogeneity of the disease; the effects of neprilysin inhibition in patients in the trial with obesity or type 2 diabetes have not yet been presented.…”
Section: Discussionmentioning
confidence: 99%
“…The combination of obesity, diabetes and AF identifies patients with HFpEF with the greatest likelihood of an adverse outcome, and in one trial in HFpEF with a high prevalence of these risk factors, angiotensin receptor blockade reduced the risk for hospitalization for HF . The addition of neprilysin inhibition to angiotensin receptor blockade (sacubitril/valsartan) ameliorates the structural and functional consequences of the atrial and ventricular myopathy seen in HFpEF; whether the drug reduces the risk for hospitalization for HF or the incidence of AF in obesity‐ or diabetes‐related HFpEF is currently under investigation …”
Section: Therapeutic Challenges In Patients With a Metabolic Disordermentioning
confidence: 99%
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“…Trial A with a P ‐value of 0.049 and trial B with a P ‐value of 0.051 may be viewed by some from a binary lens despite the narrow difference in probability estimates. The global phase 3 PARAGON‐HF (Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction) trial examining sacubitril/valsartan in HF with preserved ejection fraction narrowly missed statistical significance for its primary endpoint at an alpha threshold of 0.05 . As the HF clinical trial community interprets aggregate data results from this trial and other important RCTs due to report in the next year, we are hopeful that individual P ‐values are appropriately contextualized and not interpreted narrowly.…”
Section: A Path Forward?mentioning
confidence: 99%
“…With the recent completion of PARAGON‐HF, the angiotensin–neprilysin inhibitor sacubitril/valsartan has been added to the growing list of medications without convincing benefit in heart failure with preserved ejection fraction (HFpEF). The cardiology community is once again faced with the question of how to move forward in identifying therapies for HFpEF.…”
Section: Suggested Dimensions For Unsupervised Machine Learning and Cmentioning
confidence: 99%