Drug | Trial name (patients recruited) | Condition (study arms) | Findings (in treatment arm) |
Nesiritide | VMAC (n=489) | ADHF (nesiritide vs IV GTN vs placebo) |
|
ASCEND-HF (n=7141) | ADHF (nesiritide vs placebo) |
| |
META ANALYSIS: risk of worsening renal function (n=1269) | ADHF (nesiritide vs inotropic/non-inotropic control) |
| |
Ecadotril | US Ecadotril Pilot Safety Study (n=50) | CHF (NYHA II–III) (ecadotril 50–400 mg vs placebo) |
|
International, Multicentre Ecadotril Dose-Ranging Study (n=279) | CHF (NYHA II–III) (ecadotril 50, 100, 200 and 400 mg vs placebo) |
| |
Candoxatril | Northridge et al (n=60) | CHF (NYHA I–III) (candoxatril vs captopril vs placebo) |
|
Westheim et al (n=47) | CHF (NYHA I–II) (candoxatril vs furosemide vs placebo) |
| |
Kentsch et al (n=24) | CHF (candoxatril vs placebo) |
| |
Omapatrilat | IMPRESS (n=573) | CHF (NYHA II–IV) (omapatrilat vs lisinopril) |
|
OVERTURE (n=5770) | CHF (NYHA II–IV) (omapatrilat vs enalapril) |
| |
OCTAVE (n=25 302) | Untreated / uncontrolled HPT (omapatrilat vs enalapril) |
| |
Sacubitril /valsartan | PARADIGM-HF (n=8442) | CHF (NYHA II–IV & HFrEF: EF≤40%) (sacubitril/valsartan vs enalapril) |
|
PARAMOUNT (n=301) | CHF (NYHA II–III & HFpEF: EF≥45%) (sacubitril/valsartan vs valsartan) |
| |
PARAGON-HF (currently recruiting) | CHF (NYHA II–IV & HFpEF: EF≥45%) (sacubitril/valsartan vs valsartan) |
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VMAC: Young et al. Vasodilation in the Management of Acute Congestive Heart Failure. Circulation 2000;102:2794.
ASCEND-HF: O’Connor et al. Effect of nesiritide in patients with acute decompensated heart failure. The New England Journal of Medicine 2011;365(1):32–43.
META-ANALYSIS: Sackner-Bernstein et al. Risk of worsening renal function with nesiritide in patients with acutely decompensated heart failure. Circulation. 2005;111(12):1487–1491.
U.S. Ecadotril Pilot Safety Study: O’Connor et al. A randomized trial of ecadotril versus placebo in patients with mild to moderate heart failure: the US ecadotril pilot safety study. American Heart Journal 138,1140–1148. International, Multicentre Ecadotril Dose-ranging Study:Cleland et al. Lack of efficacy of neutral endopeptidase inhibitor ecadotril in heart failure. The International Ecadotril Multicentre Dose-Ranging Study Investigators. Lancet 351, 1657–1658. Northridge et al: Northridge et al. Placebo-controlled comparison of candoxatril, an orally active neutral endopeptidase inhibitor, and captopril in patients with chronic heart failure. European Journal of Heart Failure 1999;1 (1):67–72. Westheim et al: Westheim et al. Hemodynamic and neuroendocrine effects for candoxatril and frusemide in mild stable chronic heart failure. Journal of the American College of Cardiology. 15 Nov 1999;34(6):1794–1801. Kentsch et al: Kentsch et al. Neutral endopeptidase 24.11 inhibition may not exhibit beneficial haemodynamic effects in patients with congestive heart failure. European Journal of Clinical Pharmacology 1996;51(3-4):269–272.
IMPRESS: Rouleau et al. Comparison of vasopeptidase inhibitor, omapatrilat, and lisinopril on exercise tolerance and morbidity in patients with heart failure: IMPRESS randomised trial. Lancet. 2000;356 (9230):615–620.
OVERTURE: Packer et al. Comparison of omapatrilat and enalapril in patients with chronic heart failure: the Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events (OVERTURE). Circulation. 2002;106(8):920OC–926.
OCTAVE: Kostis et al. Omapatrilat and enalapril in patients with hypertension: the Omapatrilat Cardiovascular Treatment vs. Enalapril (OCTAVE) trial. American Journal of Hypertension. 2004;17(2):103–111.
PARADIGM-HF: McMurray et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. The New England Journal of Medicine. 2014;371(11):993–1004. PARAMOUNT: Solomon SD, Zile M, Pieske B, et al. The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomised controlled trial. Lancet. 2012;380 (9851):1387–1395. PARAGON: Clinical trials identifier: NCT01920711.
ADHF, acute decompensated heart failure; AF, atrial fibrillation; ANP, atrial natriuretic peptide; BP blood pressure; cGMP, cyclic guanosine monophosphate; CV, cardiovascular; EF, ejection fraction; GTN, glyceryl trinitrate; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HPT, hypertension; IV, intravenous; LVEF, left ventricular ejection fraction; MI, myocardial infarction; NNT, number needed to treat; NT-proBNP, N-terminal pro B-type natriuretic peptide; NYHA, New York Heart Association; PA, pulmonary artery; PCWP, pulmonary capillary wedge pressure; PVR, pulmonary vascular resistance; RRR, relative risk rate.