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Angiotensin receptor neprilysin inhibition and renal function and in heart failure: results from PARADIGM-HF
Authors : K Damman (Glasgow,GB), K Andersen (Reykjavik,IS), J Belohlavek (Prague,CZ), M P Lefkowitz (Hanover,US), J L Rouleau (Montreal,CA), S D Solomon (Boston,US), K Swedberg (Gothenburg,SE), M Zile (Charleston,US), M Packer (Dallas,US), J J V Mcmurray (Glasgow,GB)
K. Damman1
,
K. Andersen2
,
J. Belohlavek3
,
M.P. Lefkowitz4
,
J.L. Rouleau5
,
S.D. Solomon6
,
K. Swedberg7
,
M. Zile8
,
M. Packer9
,
J.J.V. McMurray1
,
1University of Glasgow - Glasgow - United Kingdom
,
2University of Iceland - Reykjavik - Iceland
,
3General University Hospital - Prague - Czech Republic
,
4Novartis Pharmaceutical Corporation - Hanover - United States of America
,
5University of Montreal - Montreal - Canada
,
6Brigham and Women's Hospital - Boston - United States of America
,
7University of Gothenburg - Gothenburg - Sweden
,
8Medical University of South Carolina - Charleston - United States of America
,
9University of Texas Southwestern Medical School - Dallas - United States of America
,
On behalf: PARADIGM-HF Committees and Investigators
Background: ACE inhibitors often reduce glomerular filtration rate (GFR) in patients with heart failure (HF). We compared the effect of the Angiotensin Receptor Neprilysin Inhibitor (ARNI) LCZ696 to enalapril on renal function and clinical outcomes in the Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial (PARADIGM-HF).
Methods: 8399 patients with HF and reduced ejection fraction were included in PARADIGM-HF. The primary endpoint was the composite of cardiovascular death or HF hospitalization (CVD/HFH). We determined the change in GFR over time and the interaction between eGFR at baseline and the effect of randomized treatment using mixed effect repeated measures analysis, adjusted for age, gender, region, time and ethnicity. We also examined the interaction between baseline chronic kidney disease (CKD, eGFR <60 mL/min/1.73m2), randomized treatment and clinical outcomes.
Results: Baseline GFR was 67.7 mL/min/1.73m2, and 36% of patients had CKD. Overall, estimated GFR decreased 7.7 mL/min/1.73m2 over the course of the study (48 months). GFR changed −0.14 and −0.11 mL/min/1.73m2 per month in the enalapril and LCZ696 groups, respectively (P=0.01). Patients treated with LCZ696 had a numerically lower incidence of renal dysfunction compared with enalapril, despite a greater fall in BP. LCZ696 reduced the risk of CVD/HFH similarly in patients with and without baseline CKD: hazard ratio 0.790 (0.691, 0.902) vs 0.799 (0.711, 0.897), respectively [P=0.90 for interaction, Figure]. A similar finding was seen for all-cause mortality.
Conclusion: The ARNI LCZ696 had a favorable cardiorenal profile compared with enalapril, with slower progression of renal dysfunction and improved clinical outcomes, even in patients with CKD.
