Key result
Higher baseline natriuretic peptides linked to ~64% higher 2-month cardiovascular death or worsening HF.
Why the study?
The prognostic associations between admission natriuretic peptide levels and early outcomes in ADHF are less known than in chronic HF. Additionally, whether a threshold NP value exists above which the clinical benefits of SGLT2i are diminished was uncertain.
Does in-hospital initiation of dapagliflozin reduce cardiovascular death or worsening heart failure through 2 months across varying baseline natriuretic peptide levels in patients hospitalized for acute decompensated heart failure?
RCT (n=2,400)
Double-blind
Randomized
Does in-hospital initiation of dapagliflozin reduce cardiovascular death or worsening heart failure through 2 months across varying baseline natriuretic peptide levels in patients hospitalized for acute decompensated heart failure?
In patients hospitalized for acute decompensated heart failure, baseline natriuretic peptide levels strongly predict early adverse clinical outcomes and symptomatic hypotension, while the relative benefit of in-hospital dapagliflozin initiation remains consistent across all natriuretic peptide tertiles.
Baseline natriuretic peptide levels stratify early risk after acute HF hospitalization; confirms prognostic value while extending consistent dapagliflozin benefit across levels.
Background The prognostic value of natriuretic peptide (NP) levels is established in chronic heart failure (HF), but less is known about the prognostic associations between admission NP levels and early outcomes in acute decompensated heart failure (ADHF). Moreover, some contemporary HF therapies appear to be less efficacious in patients with markedly elevated NP levels, and whether there exists a threshold NP value above which the clinical benefits of SGLT2i are diminished is of interest. Purpose DAPA ACT HF-TIMI 68 was a randomized, double-blind, placebo-controlled trial of in-hospital initiation of dapagliflozin in patients hospitalized for ADHF. We examined: (1) correlations between baseline NP levels and markers of congestion, (2) associations between baseline NP levels and early clinical outcomes, and (3) comparative treatment effects of dapagliflozin vs. placebo by baseline NP levels. Methods Patients enrolled in DAPA ACT HF-TIMI 68 were required to have elevated NP levels (either NT-proBNP or BNP). For this analysis, baseline NP values (measured locally) were log-transformed and normalized as Z-scores based on the distribution within the trial cohort. Tertiles of normalized NP values were compared. Congestion markers included dyspnea, orthopnea, fatigue, JVD, pulmonary rales, and peripheral edema. The primary outcome was adjudicated cardiovascular death or worsening heart failure (CVD/WHF) through 2 months. Symptomatic hypotension was a key safety outcome. Cox models were adjusted for age, eGFR, LVEF, prior HF hospitalization, prior stroke, atrial fibrillation, and use of non-invasive ventilation. Results Of 2400 participants, the median age was 69 years, 34% were women, and 72% had HFrEF. Median NT-proBNP levels for each tertile were 2366 (Q1-Q3, 1882-2843), 4888 (4123-5820), and 11,717 (8888-17,883) pg/ml, and respective median BNP levels were 617 (500-717), 1090 (957-1259), and 2322 (1820-2994) pg/ml. Clinical congestion parameters were poorly correlated with baseline NP levels (all correlation coefficients <0.1). There was a direct monotonic relationship between baseline NP level and risk of the primary outcome, with an apparent upward inflection with values above the mean (Z-scores >0) (Fig A). This risk relationship persisted after multivariable adjustment (adj-HR for T3 vs. T1, 1.64 [95% CI, 1.20-2.25]; p=0.002). Rates of symptomatic hypotension were also higher across increasing NP tertiles (T3 vs. T1: 3.9% vs. 1.8%; p=0.01). The relative treatment effect of dapagliflozin vs. placebo on CVD/WHF over 2 months appeared generally consistent across NP tertiles (Fig B). Conclusions In a large contemporary ADHF trial, baseline NP levels were minimally associated with congestion markers but strongly associated with early risk of clinical outcomes. While participants with higher baseline NP levels are at higher risk of adverse events, they may also derive greater absolute treatment benefit from dapagliflozin.
No takes yet. Share an insight, caveat, or question.
O'Meara et al. (2026) conducted an RCT in Acute decompensated heart failure (n=2,400). Dapagliflozin (and baseline natriuretic peptide tertiles) vs. Placebo (and lowest natriuretic peptide tertile) was evaluated on Adjudicated cardiovascular death or worsening heart failure (CVD/WHF) through 2 months (adj-HR 1.64, 95% CI 1.20-2.25, p=0.002). Higher baseline natriuretic peptide levels (T3 vs T1) increased 2-month cardiovascular death or worsening HF (adj-HR 1.64; 95% CI 1.20-2.25; p=0.002), with consistent dapagliflozin benefit.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: