Interaction Between Baseline and Early Worsening of Renal Function and Efficacy of Renin–Angiotensin–Aldosterone System Blockade in Patients with Heart Failure: Insights from the Val-HeFT Study

AIMS: We evaluated the effect of (dual) renin-angiotensin-aldosterone system (RAAS) blockade with valsartan and an ACE inhibitor [92.7% of patients were treated with an ACE inhibitor in the Valsartan in Heart Failure Trial (Val-HeFT)] in patients with NYHA class II-IV heart failure (HF) and reduced EF on cardiovascular (CV) death and HF hospitalization by subgroups and by presence of early worsening of renal function (EWRF) and according to baseline estimated glomerular filtration rate (eGFR). METHODS AND RESULTS: We analysed the data from 5010 patients enrolled in the Val-HeFT study. A total of 2346 (46.8%) patients had baseline renal impairment (i.e. baseline eGFR <60 mL/min/1.73 m(2)). Further, 425 patients (8.6%) had EWRF (i.e. eGFR decrease >20% within 1 month after randomization), whereas 4503 patients (91.4%) had ≤20% decline in eGFR. Overall, the difference between valsartan and placebo on the composite endpoint of CV death and HF hospitalization was significant [P = 0.0005; hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.75-0.92)]. In patients with baseline renal impairment, the difference between the treatment groups was also significant (P = 0.0002; HR 0.76, 95% CI 0.66-0.88). Patients with EWRF had higher risk of CV death and HF hospitalization vs. those without ERWF (P < 0.0001; HR 1.44, 95% CI 1.21-1.71), and within the EWRF group a significant difference was also observed between valsartan and placebo (P = 0.0086; HR 0.63, 95% CI 0.45-0.89). However, the interaction between treatment and eGFR at Month 1 was not significant (P = 0.1160). CONCLUSION: Benefits were maintained in patients with renal dysfunction at baseline and those who experienced EWRF.