Renal effects of lcz696 in patients with heart failure and preserved ejection fraction: results from paramount

Abstract

Background: In a randomized double blind trial, the angiotensin receptor neprilysin Inhibitor (LCZ696) reduced NT-proBNP and was associated with left atrial reverse remodeling and improvement in symptoms in patients with heart failure with preserved ejection fraction (HFpEF). We assessed the effect of LCZ696 on renal function. Methods: 301 HFpEF patients (NYHA II-III, left ventricular ejection fraction ≥45%, NT-proBNP>400 pg/mL) were randomly assigned to LCZ696 (200 mg b.i.d.) orvalsartan (160 mg b.i.d.). We studied renal function (detected as eGFR, urinary albumin creatinine ratio [UACR], cystatin C) at baseline, and after 36 weeks of treatment. Results: Mean age of the patients was 71±9.1 years, and mean eGFR at baseline was 65.4±20.4 ml/min/1.73m2. At 36 weeks blood pressure dropped to a greater extent in the LCZ696 treated patients (7.5±15/5.1±10.8 in the LCZ group vs. 1.5±16/0.34±11.5 in the valsartan groups; p=0.006 for systolic and p=0.001 for diastolic differences). In the LCZ696 treated patients eGFR declined less than in the valsartan group (LCZ696, -1.6 mL/min per 1.73 m2 vs valsartan, -5.2 mL/min per 1.73 m2; p=0.007), which was paralleled by changes in Cystatin C (LCZ696 group, 0.06±0.22vs valsartan group, 0.12±0.31 mg/L; p=0.012). Over 36 weeks UACR increased to a greater extent in the LCZ696 group (LCZ696, 1.9 mg/mmol at baseline, 2.9 mg/mmol at week 36; valsartan, 2.0 mg/mmol at baseline, 2.0 mg/mmol at week 36; p=0.02). (Figure Presented) Conclusion: In patients with HFpEF, therapy with LCZ696 for 36 weeks was associated with maintenance of eGFR compared to valsartan therapy, despite increases in UACR.