Narrower indications

Recorded under heart failure, with no page of their own: acute heart failure, acute decompensated heart failure. Their evidence is graded on this page rather than split across pages that would each hold a single row.

Compounds with a graded row

Ordered by rung, strongest first. The rung rates the study design; the chip beside it says what the study measured. Both are needed.

1. Nesiritide

   human RCT Direct outcome Approved for this condition

   Who was studied

   adults hospitalised with acute decompensated heart failure (dyspnoea at rest or on minimal exertion), n=7141, infusion 24-168 hours, follow-up 30 days; no ejection fraction criterion, so both reduced and preserved ejection fraction were enrolled and results are not reported separately by heart failure type

   ASCEND-HF measured the condition directly and did not find a benefit: dyspnoea improvement at 6 and 24 hours did not meet the prespecified significance threshold (44.5% vs 42.1%, P=0.03; 68.2% vs 66.1%, P=0.007), and 30-day rehospitalisation for heart failure or death from any cause was 9.4% with nesiritide versus 10.1% with placebo (P=0.31), with no difference in worsening renal function and more hypotension. FDA approved nesiritide in 2001 for acute decompensated heart failure, but the approval is historical in practice: Drugs@FDA lists the sole product, NATRECOR under NDA 020920, as Discontinued, and DailyMed carries no current nesiritide label. The trial did not stratify by ejection fraction, so nothing on file speaks to HFrEF versus HFpEF separately.

   Source PubMed 3 primary sources read for this row

2. Relaxin

   human RCT Direct outcome Not approved for this condition

   Who was studied

   adults hospitalised for acute heart failure with dyspnoea, radiographic congestion, raised natriuretic peptides, mild-to-moderate renal impairment and systolic blood pressure at least 125 mmHg; n=6545 analysed of 6600 randomised, 48-hour infusion, follow-up 180 days; no ejection fraction criterion, so HFrEF and HFpEF were both enrolled and results are not reported separately by type

   RELAX-AHF-2 tested serelaxin, the recombinant human relaxin-2 form, and did not find a benefit on either primary endpoint: cardiovascular death at 180 days occurred in 8.7% versus 8.9% with placebo (hazard ratio 0.98, 95% CI 0.83-1.15, P=0.77) and worsening heart failure at day 5 in 6.9% versus 7.7% (hazard ratio 0.89, 95% CI 0.75-1.07, P=0.19), with no difference in all-cause death, rehospitalisation, or length of stay. This confirmatory trial did not reproduce the earlier phase 3 RELAX-AHF result, and no regulator has approved serelaxin for heart failure. Entry required raised natriuretic peptides and systolic blood pressure at least 125 mmHg, so lower-blood-pressure patients were excluded.

   Source PubMed 2 primary sources read for this row

3. Apelin

   human RCT Surrogate marker Not approved for this condition

   Who was studied

   patients with NYHA class II-III chronic heart failure, n=18, alongside 6 patients undergoing coronary angiography and 26 healthy volunteers; acute single-session infusions, no follow-up; ejection fraction not reported in the source abstract

   Randomised, double-blind, placebo-controlled acute infusion studies measured vascular and haemodynamic variables only: (Pyr1)apelin-13 caused forearm vasodilatation, and systemic infusion raised cardiac index and lowered mean arterial pressure and peripheral vascular resistance in both heart failure patients and controls. No trial on file measured symptoms, hospitalisation, or mortality, and the source does not state whether the heart failure was of reduced or preserved ejection fraction.

   Source PubMed 1 primary source read for this row

4. SS-31

   human RCT Surrogate marker Not approved for this condition

   Who was studied

   patients with stable heart failure with reduced ejection fraction, LVEF 40% or below by echocardiography at screening (mean 31% plus or minus 7%), aged 40-80, n=71, 24% female, once-daily subcutaneous elamipretide 4 mg or 40 mg or placebo for 28 days

   PROGRESS-HF measured left ventricular end-systolic volume by cardiac MRI, an imaging surrogate rather than a symptom or event, and found no difference from placebo at 4 weeks (4 mg versus placebo: difference of means -0.3, 95% CI -4.6 to 4.0, P=0.90; 40 mg versus placebo: 2.3, 95% CI -1.9 to 6.5, P=0.28), with no difference in ejection fraction either. Elamipretide holds an FDA approval as FORZINITY (NDA 215244) for a different indication, Barth syndrome, which is not an approval for heart failure. The trial enrolled only HFrEF; no HFpEF trial of elamipretide is on file.

   Source PubMed 2 primary sources read for this row

5. Urocortin

   human RCT Surrogate marker Not approved for this condition

   Who was studied

   patients with acute decompensated heart failure, n=53, urocortin-2 5 ng/kg/min or placebo infused for 4 hours as adjunct to conventional therapy, measurements to 24 hours; ejection fraction and heart failure type not reported in the source abstract

   The UNICORN study measured haemodynamic and neurohormonal variables rather than heart failure outcomes: urocortin-2 raised cardiac output (2.1 l/min versus -0.1 l/min with placebo, P<0.001) and lowered systolic blood pressure by 16 mmHg, while falls in pulmonary artery and wedge pressures did not differ from placebo and urine volume and creatinine clearance fell transiently during infusion. No trial on file measured symptoms beyond 24 hours, hospitalisation or death, and the population is not resolved into HFrEF or HFpEF.

   Source PubMed 1 primary source read for this row

6. Angiotensin (1-7)

   human RCT Mechanistic only Not approved for this condition

   Who was studied

   patients with heart failure already treated with an ACE inhibitor, n=8, single-session intrabrachial infusion; ejection fraction, NYHA class and heart failure type not reported in the source

   Recorded, and not evidence for this condition

   The only human heart failure intervention study on file measured forearm blood flow by venous occlusion plethysmography, which is a vascular measurement and not a heart failure outcome, and it found nothing: angiotensin-(1-7) had no effect alone and no effect on the response to bradykinin, while bradykinin alone caused profound vasodilatation. The authors concluded angiotensin-(1-7) is biologically inactive in the forearm circulation of these patients, in contrast to preclinical work. No study on file measured symptoms, hospitalisation or death in heart failure.

   Source PubMed 2 primary sources read for this row

7. Atrial Natriuretic Peptide (ANP)

   human observational Direct outcome Approved for this condition

   Who was studied

   adults hospitalised with acute heart failure, predominantly Japanese, mean age 75-80, n approximately 2435 pooled across 6 studies published 2008-2025; ejection fraction not consistently reported in the included studies, so HFrEF and HFpEF cannot be separated

   Recombinant alpha-human ANP (carperitide) was approved for acute heart failure in Japan in 1995 by the Japanese regulator and is used there, but a 2025 systematic review and meta-analysis pooling 2 randomised trials and 3 observational studies found no difference against control in all-cause mortality (RR 1.02, 95% CI 0.63-1.66, I-squared 66%) or heart failure hospitalisation (RR 0.98, 95% CI 0.85-1.14). Tier is set at human_observational because the pooled evidence is mostly non-randomised. No regulator outside Japan has approved ANP for this condition, and no analysis on file reports outcomes by ejection fraction.

   Source NCBI 2 primary sources read for this row

8. Adrenomedullin

   human case series Surrogate marker Not approved for this condition

   Who was studied

   patients with congestive heart failure, n=7 receiving adrenomedullin and n=7 receiving placebo, plus 7 and 6 healthy subjects respectively; single intravenous infusion at 0.05 mcg/kg/min, acute study, no follow-up; ejection fraction and heart failure type not reported in the source abstract

   A placebo-controlled acute infusion study (randomisation not stated in the source abstract) measured haemodynamics, not heart failure outcomes: in the heart failure group adrenomedullin lowered mean arterial pressure by 8 mmHg, raised cardiac index by 49%, lowered pulmonary capillary wedge pressure by 4 mmHg, and increased urine volume by 48% and sodium excretion by 42%. No study on file measured symptoms, hospitalisation or death, and the source does not say whether the patients had reduced or preserved ejection fraction.

   Source PubMed 1 primary source read for this row

9. Elabela

   animal in vivo Surrogate marker Not approved for this condition

   Who was studied

   mice with pressure-overload-induced heart failure and mice given angiotensin II; continuous ELABELA peptide infusion, with APJ knockout mice as a mechanistic control; no human study on file

   In mice, continuous ELABELA infusion suppressed pressure-overload-induced cardiac hypertrophy, fibrosis and impaired contractility, and the effect was lost in APJ knockout mice. These are rodent measurements of cardiac structure and function in a surgical model, not measurements in people; no human trial of ELABELA in heart failure is on file, and the compound record itself is marked preclinical only.

   Source DOI 1 primary source read for this row

Recorded absences

1 compound is listed here without a rung. Each row exists to mark a distinction a reader would otherwise draw wrongly, and each says what is missing rather than leaving the compound off the page.

1. Brain Natriuretic Peptide (BNP)

   No rung — nothing on file to grade Not approved for this condition

   Recorded to mark a distinction, not as evidence. BNP and NT-proBNP are measured in blood to diagnose heart failure and to gate trial entry - RELAX-AHF-2, for example, required BNP at or above 500 pg/mL - and that diagnostic use is not an indication for administering BNP. The therapeutic form of human B-type natriuretic peptide given to patients is nesiritide, which is graded on its own row; endogenous BNP itself has no graded therapeutic row here.

Checked, and nothing recorded

1 compound was checked against heart failure and produced no gradeable row.

• Urotensin II — checked, no row on file

A compound is here because someone looked and the sources did not support a row — not because nobody looked. Under the rubric, uncertainty resolves to no row, and a row resting on a vendor page or a clinic blog is worse than no row at all.