Angiotensin-Neprilysin Inhibition and Renal Outcomes in Heart Failure with Preserved Ejection Fraction

Finnian R Mc Causland, Martin P Lefkowitz, Brian Claggett, Nagesh S Anavekar, Michele Senni, Mauro Gori, Pardeep S Jhund, Martina M McGrath, Milton Packer, Victor Shi, Dirk J van Veldhuisen, Faiez Zannad, Josep Comin-Colet, Marc A Pfeffer, John J V McMurray, Scott D Solomon
Circulation 2020 August 17
Background: In patients with heart failure, chronic kidney disease (CKD) is common and associated with a higher risk of renal events than in patients without CKD. We assessed the renal effects of angiotensin/neprilysin inhibition in patients with heart failure and preserved ejection fraction (HFpEF) enrolled in PARAGON-HF. Methods: In this randomized, double-blind, event-driven trial, we assigned 4,822 patients with HFpEF to receive sacubitril/valsartan (n=2419) or valsartan (n=2403). Herein we present the results of the pre-specified renal composite outcome (time to first occurrence of either: ≥50% reduction in eGFR, end-stage renal disease, or death from renal causes), the individual components of this composite, and the influence of therapy on eGFR slope. Results: At randomization, eGFR was 63±19 ml/min/1.73m2 . At study closure, the composite renal outcome occurred in 33 patients (1.4%) assigned to sacubitril/valsartan and 64 patients (2.7%) assigned to valsartan (hazard ratio [HR], 0.50; 95%CI, 0.33 to 0.77; P=0.001). The treatment effect on the composite renal endpoint did not differ according to the baseline eGFR (<60 vs ≥ 60 ml/min/1.73 m2 (P-interaction=0.92). The decline in eGFR was less for sacubitril/valsartan compared with valsartan (-1.8 [95%CI, -2.0 to -1.6] vs. -2.4 [95%CI, -2.6 to - 2.2] ml/min/1.73m2 /year). Conclusions: In patients with HFpEF, sacubitril/valsartan reduced the risk of renal events, and slowed decline in eGFR, compared with valsartan. Clinical Trial Registration: URL: Unique Identifier: NCT01920711.

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