Key result
Renal dysfunction is linked to ~22% lower achievement of target sacubitril/valsartan doses in HFrEF after ADHF.
Why the study?
Treating HFrEF with renal dysfunction is challenging because of the risk of renal function deterioration, especially after acute decompensated heart failure.
Does early initiation of sacubitril/valsartan affect tolerability, renal function, and cardiac biomarkers in HFrEF patients with renal dysfunction following acute decompensated heart failure?
RCT (n=959)
Does early initiation of sacubitril/valsartan affect tolerability, renal function, and cardiac biomarkers in HFrEF patients with renal dysfunction following acute decompensated heart failure?
Absolute Event Rate: 42% vs 54%
p-value: p=<.001
Early initiation of sacubitril/valsartan in HFrEF patients with renal dysfunction after ADHF is generally tolerated and improves eGFR and cardiac biomarkers, though target dose achievement is lower and hyperkalemia risk is higher compared to those without renal dysfunction.
Most stabilized ADHF patients with RD tolerate early sacubitril/valsartan; leaves open dedicated RCTs for outcomes and uptitration guidance.
Background Treatment of patients with heart failure with reduced ejection fraction (HFrEF) and renal dysfunction (RD) is challenging owing to the risk of further deterioration in renal function, especially after acute decompensated HF (ADHF). Methods and Results We assessed the effect of RD (estimated glomerular filtration rate of ≥30 to <60 mL/min/1.73 m 2 ) on initiation, up-titration, and tolerability of sacubitril/valsartan in hemodynamically stabilized patients with HFrEF admitted for ADHF (RD, n = 476; non-RD, n = 483). At week 10, the target dose of sacubitril/valsartan (97/103 mg twice daily) was achieved by 42% patients in RD subgroup vs 54% in non-RD patients ( P < .001). Sacubitril/valsartan was associated with greater estimated glomerular filtration rate improvements in RD subgroup than non-RD (change from baseline least squares mean 4.1 mL/min/1.73 m 2 , 95% confidence interval 2.2–6.1, P < .001). Cardiac biomarkers improved significantly in both subgroups; however, compared with the RD subgroup, the improvement was greater in those without RD (N-terminal pro-brain natriuretic peptide, −28.6% vs −44.8%, high-sensitivity troponin T −20.3% vs −33.9%) ( P < .001). Patients in the RD subgroup compared with those without RD experienced higher rates of hyperkalemia (16.3% vs 6.5%, P < .001), investigator-reported cardiac failure (9.7% vs 5.6%, P = .029), and renal impairment (6.4% vs 2.1%, P = .002). Conclusions Most patients with HFrEF and concomitant RD hospitalized for ADHF tolerated early initiation of sacubitril/valsartan and showed significant improvements in estimated glomerular filtration rate and cardiac biomarkers. Clinical Trial Registration NCT02661217.
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Straburzyńska‐Migaj et al. (2023) conducted an RCT in Heart failure with reduced ejection fraction and renal dysfunction (n=959). Sacubitril/valsartan in patients with renal dysfunction vs. Sacubitril/valsartan in patients without renal dysfunction was evaluated on Achievement of target dose of sacubitril/valsartan at week 10 (p=<.001). In hemodynamically stabilized patients with HFrEF after ADHF, those with renal dysfunction achieved the target dose of sacubitril/valsartan less frequently than those without (42% vs 54%, P<0.001).
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