Dual RAAS Blockade with Valsartan Induces Long-Term Benefit in Patients with HF

SAN FRANCISCO, CA—Patients with systolic congestive heart failure, including those with early worsening of renal function and renal dysfunction at baseline, had long-term benefits from dual renin-angiotensin-aldosterone system (RAAS) blockade in the addition of valsartan to angiotensin-converting enzyme (ACE) inhibitor, in a post hoc analysis of results from the Valsartan in Heart Failure Trial (Val-HeFT) as concluded in a presentation at ACC.13, the American College of Cardiology's 62nd Annual Scientific Session.

Heart failure patients with compromised renal function are at a greater risk of hospitalization and death. RAAS inhibition has a long-term benefit in this population but may be associated with an initial decline in renal function. Long-term benefits may be observed with the addition of an angiotensin-receptor blocker (ARB) to an ACE inhibitor in heart failure patients with early worsening of renal function (EWRF).

Anastasia Lesogor, MD, and colleagues at Novartis Pharma AG, Basel, Switzerland analyzed the effect of valsartan on the composite endpoint of cardiovascular death and heart failure hospitalization in patients based on estimated glomerular filtration rate (eGFR) at baseline and presence of EWRF using data from Val-HeFT, a randomized double-blind, placebo-controlled, parallel-group, multicenter study conducted from March 1997–October 2000.

The clinically stable New York Heart Association Class II–IV heart failure patients (n=5,010) enrolled in the study had reduced ejection fraction and only 5,007 patients were included in this post-hoc analysis. At one month, only 4,928 patients were included in the change in eGFR analysis. Renal impairment was defined as eGFR<60mL/min/1.73 m2 at baseline, and EWRF was defined as eGFR decrease >20% within 1 month after randomization.

Baseline eGFR data was available for 5,007 patients, of which 4,644 (92.7%) were receiving ACE inhibitors. Renal impairment at baseline was observed in 2,346 (46.8%) patients and early worsening of renal function in 425 (8.6%) patients.

“Overall, patients receiving valsartan showed a significant reduction in composite cardiovascular death and heart failure hospitalization compared with placebo (hazard ratio [HR] 0.83 [0.75, 0.92]; P=0.0005),” Lesogor noted. “In patients with baseline eGFR <60mL/min/1.73 m2, dual RAAS conferred significant benefit in favor of valsartan on cardiovascular death and heart failure hospitalization as compared to placebo (HR 0.76 [0.66, 0.88]; P=0.0002).”

Patients with (vs. without) early worsening of renal function had a significantly higher risk of cardiovascular death and heart failure hospitalization (HR 1.44 [1.21, 1.71]; P<0.0001). A significant difference between treatment groups was also observed in favor of valsartan (dual RAAS) in these patients (HR 0.63 [0.45, 0.89]; P=0.0086).

Despite an initial decline in eGFR with dual RAAS inhibition, long-term renal function did not change which may have been expected in HF patients. Long-term benefits remained the same regardless of EWRF status. Dr. Lesogor concluded, “The addition of valsartan to ACE inhibitors in systolic CHF patients was beneficial even in patients with renal impairment at baseline and EWRF.”