Mechanism

treatment

comparator

All cause death

Cardiovascular death

hospitalisation for heart failure

hospitalisation for cardiovascular causes

Death from any cause or hospitalization for heart failure

CV death, MI hospitalization for HF

death or hospitalization

Cardiovascular death or hospital admission for CHF

heart failure death

30-day death

BNP under treatment

amelioration of Dyspnea at 24 h

Amelioration of Dyspnea at 6 h

Nesiritide

acute heart failure, in all type of patients

vs control

Endpoint	TE [95% CI]	p val	I2	n	k	trials
All cause death	no data
Cardiovascular death	no data
hospitalisation for heart failure	no data
hospitalisation for cardiovascular causes	no data
Death from any cause or hospitalization for heart failure	no data
CV death, MI hospitalization for HF	no data
death or hospitalization	no data
Cardiovascular death or hospital admission for CHF	no data
heart failure death	no data
30-day death	no data
BNP under treatment	no data
amelioration of Dyspnea at 24 h	no data
Amelioration of Dyspnea at 6 h	no data

TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients

Trial	Studied treatment	Control	Patients
NSGET (comparative trial), 2000	nesiritide(0.015 and 0.030 microg/kg/min	usual care	acutely decompensated heart failure requiring invasive monitoring

Nesiritide

acute heart failure, in all type of patients

vs placebo

Endpoint	TE [95% CI]	p val	I2	n	k	trials
All cause death	0.93 [0.73 1.18]	p=1.00	0	7371	3	NSGET (efficacy trial), PROACTION, ASCEND-HF,
Cardiovascular death	no data
hospitalisation for heart failure	0.98 [0.81 1.20]	p=1.00	0	7007	1	ASCEND-HF,
hospitalisation for cardiovascular causes	no data
Death from any cause or hospitalization for heart failure	0.93 [0.80 1.10]	p=1.00	0	7007	1	ASCEND-HF,
CV death, MI hospitalization for HF	no data
death or hospitalization	no data
Cardiovascular death or hospital admission for CHF	no data
heart failure death	no data
30-day death	0.90 [0.70 1.15]	p=1.00	0	7007	1	ASCEND-HF,
BNP under treatment	no data
amelioration of Dyspnea at 24 h	1.11 [1.00 1.23]	p=1.00	0	7007	1	ASCEND-HF,
Amelioration of Dyspnea at 6 h	no data

TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients

Trial	Studied treatment	Control	Patients
NSGET (efficacy trial), 2000	nesiritide(0.015 and 0.030 microg/kg/min	placebo	acutely decompensated heart failure requiring invasive monitoring
PROACTION, 2003	nesiritidefor at least 12h	placebo	patients presenting to the ED with acutely decompensated HF and dyspnea at rest or with minimal activity
BNP-CARDS, 2007	nesiritide as a 0.01-µg/kg/min infusion for 48 hours	placebo	acute decompensated heart failure with moderate to severe renal insufficiency
FUSION 2, 2008	nesiritide (2 µg/kg bolus plus 0.01 µg/kg-per-minute infusion for four to six hours)	placebo	patients with ACC/AHA stage C/D heart failure with two recent heart-failure hospitalizations, an ejection fraction of less than 40%, and NYHA class 4 symptoms or NYHA class 3 symptoms with creatinine clearance less than 60 mL/min
ASCEND-HF, 2011	intravenous nesiritide for 24 hours to 7 days on top of standard therapy	matching placebo	Patients hospitalized for heart failure (within 24 hours of hospitalization and institution of acute IV therapy for ADHF)
VMAC (intravenous neseritide), 2002	intravenous nesiritidefor 3 hours	placebo	acutely decompensated heart failure requiring hospitalization

Nesiritide

acute heart failure, in all type of patients

vs dobutamine

Endpoint	TE [95% CI]	p val	I2	n	k	trials
All cause death	no data
Cardiovascular death	no data
hospitalisation for heart failure	no data
hospitalisation for cardiovascular causes	no data
Death from any cause or hospitalization for heart failure	no data
CV death, MI hospitalization for HF	no data
death or hospitalization	no data
Cardiovascular death or hospital admission for CHF	no data
heart failure death	no data
30-day death	no data
BNP under treatment	no data
amelioration of Dyspnea at 24 h	no data
Amelioration of Dyspnea at 6 h	no data

TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients

Trial	Studied treatment	Control	Patients
PRECEDENT, 2002	nesiritide(0.015 or 0.03 microg/kg/min)	Dobutamine (> or =5 microg/kg/min)	Symptomatic, Decompensated CHF

Nesiritide

acute heart failure, in all type of patients

vs nitroglycerin

Endpoint	TE [95% CI]	p val	I2	n	k	trials
All cause death	1.56 [0.76 3.19]	p=1.00	0	498	1	VMAC (24h),
Cardiovascular death	no data
hospitalisation for heart failure	no data
hospitalisation for cardiovascular causes	no data
Death from any cause or hospitalization for heart failure	no data
CV death, MI hospitalization for HF	no data
death or hospitalization	no data
Cardiovascular death or hospital admission for CHF	no data
heart failure death	no data
30-day death	no data
BNP under treatment	no data
amelioration of Dyspnea at 24 h	no data
Amelioration of Dyspnea at 6 h	no data

TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients

Trial	Studied treatment	Control	Patients
VMAC (24h), 2002	nesiritideinfusion for 24 hours	nitroglycerin	acutely decompensated heart failure requiring hospitalization

Nesiritide

acute heart failure, in all type of patients

vs standard care

Endpoint	TE [95% CI]	p val	I2	n	k	trials
All cause death	no data
Cardiovascular death	no data
hospitalisation for heart failure	no data
hospitalisation for cardiovascular causes	no data
Death from any cause or hospitalization for heart failure	no data
CV death, MI hospitalization for HF	no data
death or hospitalization	no data
Cardiovascular death or hospital admission for CHF	no data
heart failure death	no data
30-day death	no data
BNP under treatment	no data
amelioration of Dyspnea at 24 h	no data
Amelioration of Dyspnea at 6 h	no data

TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients

Trial	Studied treatment	Control	Patients
FUSION 1, 2004	nesiritide 0.005 microg/kg/min or 0.010 microg/kg/min once weekly	standard care	outpatient with co-morbid advanced heart failure and renal insufficiency

Levosimendan

acute heart failure, in all type of patients

vs placebo

Endpoint	TE [95% CI]	p val	I2	n	k	trials
All cause death	no data
Cardiovascular death	no data
hospitalisation for heart failure	no data
hospitalisation for cardiovascular causes	no data
Death from any cause or hospitalization for heart failure	no data
CV death, MI hospitalization for HF	no data
death or hospitalization	no data
Cardiovascular death or hospital admission for CHF	no data
heart failure death	no data
30-day death	no data
BNP under treatment	no data
amelioration of Dyspnea at 24 h	no data
Amelioration of Dyspnea at 6 h	no data

TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients

Trial	Studied treatment	Control	Patients
REVIVE II, 2013	Intravenous Levosimendan	placebo	patients with decompensated chronic heart failure
REVIVE-I, 2003	levosimendan 0.1–0.2 mg/kg/min	placebo	patienst with HF andsymptoms at rest
RUSSLAN, 2002	Levosimendan at different doses (0.1-0.4 microg x kg(-1) x min(-1)) for 6h	placebo	patients with left ventricular failure complicating acute myocardial infarction

Levosimendan

acute heart failure, in all type of patients

vs dobutamine

Endpoint	TE [95% CI]	p val	I2	n	k	trials
All cause death	no data
Cardiovascular death	no data
hospitalisation for heart failure	no data
hospitalisation for cardiovascular causes	no data
Death from any cause or hospitalization for heart failure	no data
CV death, MI hospitalization for HF	no data
death or hospitalization	no data
Cardiovascular death or hospital admission for CHF	no data
heart failure death	no data
30-day death	no data
BNP under treatment	no data
amelioration of Dyspnea at 24 h	no data
Amelioration of Dyspnea at 6 h	no data

TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients

Trial	Studied treatment	Control	Patients
SURVIVE, 2007	Intravenous levosimendan	intravenous dobutamine	patients hospitalized with acute decompensated heart failure who required inotropic support
CASINO, 0	Levosimendan 16 mg/kg þ 0.2 mg/kg/min	Dobutamine (10 mg/kg/min) and placebo	patients withdecompensatedlow-output HF
LIDO, 2002	Levosimendan	Dobutamine	patients with low-output heart failure

Serelaxin

acute heart failure, in all type of patients

vs placebo

Endpoint	TE [95% CI]	p val	I2	n	k	trials
All cause death	no data
Cardiovascular death	no data
hospitalisation for heart failure	no data
hospitalisation for cardiovascular causes	no data
Death from any cause or hospitalization for heart failure	no data
CV death, MI hospitalization for HF	no data
death or hospitalization	no data
Cardiovascular death or hospital admission for CHF	no data
heart failure death	no data
30-day death	no data
BNP under treatment	no data
amelioration of Dyspnea at 24 h	no data
Amelioration of Dyspnea at 6 h	no data

TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients

Trial	Studied treatment	Control	Patients
Pre-RELAX-AHF, 2009	intravenous relaxin for 48 hours: 10µg/kg daily, 30µg/kg daily, 100µg/kg daily, 250µg/kg daily	placebo	Patients hospitalized with acute heart failure
RELAX-AHF, 2013	48-h intravenous infusions of placebo or serelaxin (30 ìg/kg per day) within 16 h from presentation	placebo (on top stnadard care)	patients admitted to hospital for acute heart failure

Rolofylline

acute heart failure, in all type of patients

vs placebo

Endpoint	TE [95% CI]	p val	I2	n	k	trials
All cause death	no data
Cardiovascular death	no data
hospitalisation for heart failure	no data
hospitalisation for cardiovascular causes	no data
Death from any cause or hospitalization for heart failure	no data
CV death, MI hospitalization for HF	no data
death or hospitalization	no data
Cardiovascular death or hospital admission for CHF	no data
heart failure death	no data
30-day death	no data
BNP under treatment	no data
amelioration of Dyspnea at 24 h	no data
Amelioration of Dyspnea at 6 h	no data

TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients

Trial	Studied treatment	Control	Patients
PROTECT, 2010	daily intravenous rolofylline (30 mg) for up to 3 days	placebo	patients hospitalized for acute heart failure with impaired renal function

new drug under development