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UKidney Nephrology News and Insights

Effect of angiotensin-neprilysin inhibition on renal outcomes in heart failure with preserved ejection fraction

Effect of angiotensin-neprilysin inhibition on renal outcomes in heart failure with preserved ejection fraction

Session: High-Impact Clinical Trials

Presenter: Finnian R. McCausland, MBBCh, MMSc, FRCPI, PG CertMedEd, Assistant Professor, Harvard Medical School

Dr. Danielle KirkmanFinnian R. McCausland

Looking out to a booked-solid room, Finnian R. McCausland, MBBCh, relayed the results of a trial concerning the effects of angiotensin-neprilysin inhibition on renal outcomes in patients with preserved ejection fraction.


Heart failure with preserved ejection fraction (HFpEF) not only accounts for half of all heart failure cases, but also continues to rise in prevalence. Patients who have kidney disease along with HFpEF tend to have poor outcomes with suboptimal treatment options available.

The long-term kidney effects of the neprilysin inhibitor sacubitril and the angiotensin receptor blocker valsartan (sacubitril/valsartan), a combination that relieves congestion while simultaneously lowering blood pressure, was investigated.

Study Population

A total of 4,822 patients diagnosed with HFpEF from the PARAGON-HF trial were included in this investigation. Key inclusion criteria included greater than or equal to 50 years and LVEF greater than or equal to 45 percent, HYHA II-IV heart failure (HF) (requiring diuretics for at least 30 days prior to enrollment), structural heart disease defined by LAE or LVH by echocardiography within 6 months, and elevated NTproBNP (if hospitalized for HF within 9 months: 200 pg/ml; if not hospitalized: 300 pg/ml). 

Results and Interpretation

In patients with HF and preserved ejection fraction, sacubitril/valsartan combination resulted in fewer renal events when compared to valsartan alone. What drove this finding was fewer occurrences of a sustained decline in eGFR of greater than or equal to 50 percent. The combination therapy weakened the rate of decline in eGFR compared to just valsartan. *This finding is also consistent with analyses pulled from PARADIGM-HF in HFrEF. Although more episodes of hypotension were observed, data from this investigation show a benefit of the combination sacubitril/valsartan in patients with HFpEF, no matter what baseline eGFR reads.

Overall, although based on hypotheses, a greater benefit from the combination therapy was observed to result in a reduction of HF and hospitalizations and CV death among patients with HFpEF and lower baseline eGFR.

According to lead author and presenter at this session, Finnian McCausland, MBBCh, “Future studies are required to investigate the reasons for these benefits and to determine which patients will benefit most.”

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