Thread by @FrailtyMD

#Tweetorial PIONEER-HF Trial: Angiotensin–Neprilysin Inhibition in Acute Decompensated Heart Failure pubmed.com/30415601

▶️ Double-blind RCT at 129 US hospitals, ITT analysis

🅿️ N=881 hospitalized patients
- Primary Dx of ADHF (1/3 new Dx)
- LVEF ≤40%
- NTproBNP ≥1600 or BNP ≥400
- GFR ≥30
- SBP ≥100
- No IV nitro or increase in IV diuretics within 6h
- Age IQR 51-71
- Day of enrolment IQR 2-4

ℹ️ Entresto

* 1/2 previously on ACEI/ARB, if on ACEI then took placebo on first trial day (36h washout)

©️ Enalapril

🅾️ Primary: NTproBNP or BNP ratio of the geometric mean of values at weeks 4 and 8 to the value at baseline -> -47% vs. -25%, ratio 0.71 (0.63, 0.81)

“efficacy variables including changes in BNP are standard for the evaluation of therapeutic agents in heart failure” (really...)

🅾️ Secondary: Death, rehospitalization for HF, listing for Txp, or LVAD -> 9% vs. 17%, HR 0.54 (0.37, 0.79)

* Added to the list of exploratory endpoints in 5/2018

🅾️ Safety: Discontinuation due to ADE -> 12% vs. 10%, nonsignificant

1. Symptomatic hypotension
2. Worsening renal function
3. Hyperkalemia

“initiation of any neurohormonal agent in this population should be performed cautiously” (true!)

🤔 Top 3 limitations
#1 Weak surrogate efficacy endpoint
#2 Wide CIs for safety endpoints with concerning # ADE in both groups ?2/2 rapid drug up-titration based on only BP and not Cr
#3 Very few patients 80+

* 15% missing BNP at f/u but results similar with multiple imputation