Table 2.

Main randomized clinical trials on ARNIs in patients with HFpEF with improved soft endpoints but no clear effect on CV deaths.

Study	Year	Drugs	Patients	EF	Primary endpoint	p-value	Follow-up
PARAMOUNT	2012	Sacubitril/valsartan vs. valsartan	149	$\ge$45%	Change from baseline in NT-proBNP level at week 12 [68]	p = 0.01	36 weeks
PARAGON-HF	2019	Sacubitril/valsartan vs. valsartan	4822	$\ge$45%	Composite of total hospitalizations for HF and death from CV causes [63]	p = 0.06	35 months
PARALLAX	2021	Sacubitril/valsartan vs. enalapril, valsartan, or placebo	4632	$>$40%	Change from baseline in plasma NT-proBNP level at week 12.	p 0.001	24 weeks
					Change from baseline in the 6-minute walk distance at week 24 [69]	p = 0.42
PARAGLIDE	2023	Sacubitril/valsartan vs. valsartan	466	$>$40%	Time averaged reduction in NT-proBNP after an acute HF episode [71]	p = 0049	8 weeks

ARNI, angiotensin receptor–neprilysin inhibitor; CV, cardiovascular; EF, ejection fraction; HF, heart failure; PARAMOUNT, Prospective Comparison of ARNI with ARB on Management of Heart Failure with Preserved Ejection Fraction; PARAGON-HF, Prospective Comparison of ARNI with ARB Global Outcomes in HFpEF; PARALLAX, Prospective Comparison of ARNI vs. Comorbidity-Associated Conventional Therapy on Quality of Life and Exercise Capacity; PARAGLIDE, prospective comparison of ARNI with ARB Given following stabiLization In DEcompensated HFpEF; HFpEF, heart failure with preserved ejection fraction; NT-proBNP, N-terminal pro-B-type natriuretic peptide; ARB, angiotensin receptor blocker.