heart failure clinical trials results

aldactone versus furosemide
Bednarz, 2000
Aldactone 200 mg i.v
versus
furosemide 20 mg i.v
patients with NYHA class III to IV congestive heart failure open
Aliskiren versus placebo
ASTRONAUT, 2013
NCT00894387
Aliskiren
versus
placebo
stable patients with heart failure, an LVEF <40% (mean 28%), and elevated natriuretic peptides who had been discharged from a heart-failure hospitalization an average of five days beforedouble blind
Follow-up duration: 6 months
North and South america, Europe, Asia
amiloride versus placebo
Cheitlin, 1991
amiloride
versus
placebo
men with a history of congestive heart failure double blind
Follow-up duration: 12 weeks
amiodarone versus ICD
AMIOVIRT, 2003
amiodarones
versus
implantable cardioverter-defibrillatorag
patients with nonischemic dilated cardiomyopathy, asymptomatic nonsustained ventricular tachycardia, and left ventricular ejection fraction <=0.35
Follow-up duration: 2 y
US
amiodarone versus no treatment
GESICA, 1994
amiodarone 300 mg/day
versus
no treatment
patients with severe heart failure Any two of CTR >0·55, LVEF<=35%, echo LVED >3·2 cm/m2open
Follow-up duration: 1·10 years
EPAMSA, 1985
amiodarone 400 mg/day
versus
no treatment
patients with reduced left ventricular ejection fraction ( < 35%) and asymptomatic ventricular arrhythmias (Lown classes 2 and 4) LVEF <=35% and Lown class 2–5open
Follow-up duration: 0·81 years
amiodarone versus placebo
Nicklas, 1991
amiodarone 200 mg/day
versus
placebo
patients with ejection fractions less than 30%, New York Heart Association class III or IV symptoms, and frequent but asymptomatic spontaneous ventricular ectopy (Lown class II to V) LVEF <=30% and Lown class 2–5double blind
Follow-up duration: NA
Hamer, 1989
amiodarone 200 mg/day
versus
placebo
patients with severe congestive heart failure but no sustained ventricular arrhythmiadouble blind
Follow-up duration: 1·63 years
STATCHF, 1995
amiodarone 200 mg/day
versus
placebo
patients with symptoms of congestive heart failure, cardiac enlargement, 10 or more premature ventricular contractions per hour, and a left ventricular ejection fraction of 40 percent or less LVEF <=40% and >=10 VPD/h and LVED >=55 mm or CTR >0·55double blind
Follow-up duration: 2·15 years
amlodipine versus control
Packer, 1991
amlodipine
versus
CHD multiple cause, NYHA class II-IIIDouble blind
Follow-up duration: 2 months
Smith, 1994
amlodipine
versus
CHD multiple cause, NYHA class II-IIIDouble blind
Follow-up duration: 3 months
Binkley, 1996
amlodipine
versus
CHD multiple cause, NYHA class II-IIIDouble blind
Follow-up duration: 3 months
Udelson, 1996
amlodipine
versus
patients with congestive heart failure due to ischaemic heart disease, NYHA class II-IIIDouble blind
Follow-up duration: 3 months
Ghali, 1997
amlodipine
versus
CHD multiple cause, NYHA class III-IVDouble blind
Follow-up duration: 3 months
amlodipine versus placebo
PRAISE, 1996
amlodipine 10 mg once daily
versus
placebo
patients with severe chronic heart failure and ejection fractions of less than 30 percent applDouble blind
Follow-up duration: median 13.8 mo (range 6-33 mo)
US
Amlodipine versus placebo
PRAISE II , 2000
Amlodipine
versus
placebo
heart failure in non ischemic cardiomyopathy
Follow-up duration: up to 4 years
Amrinone versus placebo
AMTG, 1985
Amrinone <600mg/day
versus
placebo
patients with heart failure NYHA III/IVdouble blind
Follow-up duration: 3 months
aspirin versus no treatment
WASH (aspirin), 2004
aspirin 300 mg/day
versus
no treatment
patients with heart failure and left ventricular systolic dysfunction requiring diuretic therapy with LVEF<=35% open
Follow-up duration: 27 months
UK, US
aspirin versus placebo
Barzizza (ASA), 1993
aspirin 300mg
versus
placebo
patients with dilated cardiomyopathy and evidence of intraventricular thrombiNA
Follow-up duration: 6 months
atorvastatin versus control
Wojnicz, 2006
atorvastatin 40 mg/day
versus
conventional treatment for heart failure
patients with inflammatory dilated cardiomyopathy (DC) (positive immunohistochemistry results on endomyocardial biopsy)open
Follow-up duration: 6 months
Yamada, 2007
atorvastatin 10 mg/d
versus
standard treatment
outpatients with mild to moderate CHF and radionuclide left ventricular ejection fraction (LVEF) <40%
Follow-up duration: mean 2.58y
atorvastatin versus placebo
Strey, 2005
atorvastatin 40mg
versus
placebo
patients with stable, symptomatic heart failure (New York Heart Association Class II or III) and a left ventricular ejection fraction <40%
Follow-up duration: 6 weeks
Sola, 2006
atorvastatin 20 mg/day
versus
placebo
patients with nonischemic HF and a left ventricular ejection fraction (LVEF) <=35%double blind
Follow-up duration: 1y
benazepril versus control
McGany, 1991

versus
benazepril versus placebo
Colfer, 1992
benazepriltitrated up to 20mg daily
versus
placebo
Patients with chronic New York Heart Association class II to IV symptoms of CHF and an ejection fraction by radionuclide scanning of less than or equal to 35%double blind
Follow-up duration: 12-week
US
beta-erythropoietin versus placebo
Palazzuoli, 2006
s.c. beta-EPO for 3 months twice weekly and oral iron
versus
placebo + oral iron
patients with anemia and resistant CHFdouble blind
Bisoprolol versus placebo
CIBIS II (elderly subgroup), 1999
Bisoprolol
versus
placebo
Patients aged 71 years and older
bisoprolol versus placebo
CIBIS, 1994
bisoprolol 5mg/d
versus
placebo
stable chronic idiopathic dilated cardiomyopathy heart failure NYHA 3-4, EF<40%Double blind
Follow-up duration: 1.9 years (range 4-44 mo)
9 european countries
CIBIS II, 1999
Bisoprolol target dose 10mg/daily
versus
control
chronic herat failure, ejection fraction<=35%, NYHA 3-4Double blind
Follow-up duration: 1.3 years
western and eastern europe
BNP-guided management versus control
TIME CHF, 2009
intensive BNP-guided therapy
versus
standard symptom-guided therapy
patients with heart failure, with the specific inclusion of patients ¡Ý75 years of ageopen
PRIMA, 0
NT-proBNP guided management
versus
clinically guided management
Patients admitted for worsening heart failure and with NT-proBNP decreasing during their admission open
Follow-up duration: 702 days
the Netherlands
PROTECT, 2009
NCT00351390
natriuretic-peptide-guided therapy
versus
standard management
patients with NYHA class 2-4 heart failure, LVEF <40%, and history of at least one admission or outpatient diuretic dose increase for heart-failure destabilization in the previous six months
STARS-BNP, 2007
BNP-guidance as a supplement to clinical judgment
versus
traditional approach
patients in NYHA functional class 2-3 with an LVEF <45%; optimally treated with angiotensin-converting enzyme inhibitors (ACEIs), beta-blockers, and diuretics by CHF specialists open
Follow-up duration: 6 mo
BATTLESCARRED, 2009
ANZCTR12605000735651
drug treatment directed by plasma NTproBNP for 2 years
versus
usual care
patients admitted to hospital for HFopen
Follow-up duration: 3y
New Zealand
STARBRITE, 2007
NCT00484770
BNP-guided treatment
versus
clinically based management
patients in NYHA class 3-4 and with an LVEF <35%; enrolled prior to discharge following hospitalization for acute decompensationopen
Follow-up duration: 3 mo
Troughton, 2000
BNP-guided treatment
versus
empirical trial-based therapy dictated by clinical acumen61Ø7Ow
patients with impaired systolic function (leftventricular ejection fraction <40%) and symptomatic heart failure (New York Heart Association class II–IV); treated with ACE inhibitors, loop diuretic with or without digoxinopen
Follow-up duration: 9.5 mo (>6 mo)
UK
Bone marrow derived stem cell versus control
CUPID 2b, 2016
NCT01643330
Intracoronary Administration of MYDICAR® (AAV1/SERCA2a) (Genetically Targeted Enzyme Replacement Therapy)
versus
patients with advanced heart failure
FOCUS-CCTRN, 2012
NCT00824005
autologous bone-marrow-cell therapy
versus
patients with chronic ischemic heart failure
Pokushalov (DOUBLON DIB), 2010
Intramyocardial transplantation of autologous bone marrow mononuclear cells
versus
optimal medical therapy
patients with severe ischemic heart failure
Russia
Bone marrow derived stem cell versus placebo
ABCD, 2010
intracoronary stem cell implantation (Autologous Bone Marrow Cells)
versus
Patients with nonischemic dilated cardiomyopathy
INCL, 2015
NCT00333827
bone marrow derived stem cell
versus
placebo
patients with dilated cardiomyopathy and heart failure in NYHA class III or IV double blind
Follow-up duration: 6 months
Brazil
Bone marrow mononuclear cells versus control
Ang, 2008
transplantation of autologous bone marrow cells
versus
Elective CABG patients with established myocardial scars diagnosed as akinetic or dyskinetic segments by dobutamine stress echocardiography and confirmed at surgery single-blinded
Hendrikx, 2006
intramyocardial injection of autologous mononuclear bone marrow cells during coronary artery bypass graft
versus
patients with a postinfarction nonviable scar
Follow-up duration: 4 months
TOPCARE-CHD, 2006
NCT00289822
intracoronary transplantation of progenitor cells derived from bone marrow (BMC) or circulating blood
versus
patients with stable ischemic heart disease who had had a myocardial infarction at least 3 months previously
Yao, 2008
intracoronary bone marrow mononuclear cells
versus
patients with stable ischaemic heart disease due to a previous MI
Bone marrow mononuclear cells versus placebo
FOCUS-HF, 2011
NCT00203203.

versus
Mock injection
patients with chronic HF
Follow-up duration: 6 mo
Bone marrow progenitor cells versus control
Manginas, 2007
intracoronary administration of selected CD133(+) and CD133(-)CD34(+) progenitor cells
versus
patients with old, nonviable anterior myocardial infarction
Patel, 2005
adult autologous stem cell transplantation (CD34+)
versus
patients with ischemic cardiomyopathy and an ejection fraction of less than 35% who were scheduled for primary off-pump coronary artery bypass grafting
Perin, 2012
transendocardial injection of autologous aldehyde dehydrogenase-bright stem cells
versus
patients with advanced ischemic heart failure
Follow-up duration: 6 months
Vrtovec, 2011
NCT00629018
intracoronary transplantation of CD34+ cells
versus
patients with dilated cardiomyopathy
Vrtovec, 2013
NCT01350310
intracoronary CD34+ cell transplantation
versus
patients with dilated cardiomyopathy
Bucindolol versus placebo
Pollock, 1990
bucindolol target dose 100mg twice daily
versus
placebo
Patienst with stable, chronic heart failure with a dilated cardiomyopathy due to ischemic or isopathic causesDouble blind
Follow-up duration: 3 months
US
Woodley, 1991
bucindolol
versus
placebo
NYHA 2-3, IDC/CAD
Follow-up duration: 3 mo
MERIT-HF (elderly subgroup), 1999
Bucindolol
versus
placebo
Patients aged 65 years and olderwith chronic heart failure in NYHA functional class II-IV and with ejection fraction of 0.40 or less, stabilised with optimum standard therapy
Bristow, 1994
bucindolol
versus
placebo
NYHA 2-3, IDC
Follow-up duration: 3 mo
bucindolol versus placebo
BEST, 2001
NCT00000560
bucindolol titrated to 50mg txice daily
versus
placebo
patients with heart failure NYHA class III or IV and a left ventricular ejection fraction of 35 percent or lowerDouble blind
Follow-up duration: 2 years
US, Canada
candesartan versus enalapril
RESOLVD (candesartan alone), 1999
Candesartan, 4 mg, 8mg, 16mg daily
versus
Enalapril, 10 mg twice daily
Patients with New York Heart Association functional class NYHA II, III, or IV CHF, 6-minute walk distance (6MWD) >500 m, and ejection fraction (EF) <0.40Double blind
Follow-up duration: 43 wk
US, Canada, Europe, Brazil
candesartan versus placebo
ARCH-J, 2003
Candesartan, 8 mg daily
versus
Placebo
patients with chronic heart failure who were not receiving ACE inhibitor therapydouble blind
Follow-up duration: 155 d
CHARM-Alternative, 2003
candesartan (target dose32 mg once daily)
versus
Placebo
patients with symptomatic heart failure and left-ventricular ejection fraction 40% or less who were notreceiving ACE inhibitors because of previous intolerancedouble blind
Follow-up duration: Median, 33.7 mo
26 countries
CHARM preserved, 2003
candesartan target dose 32 mg once daily
versus
placebo
patients with NYHA II-IV heart failure and LVEF higher than 40%double blind
Follow-up duration: 36.6 months
26 countries
Mitrovic et al., 2003
Candesartan, 2 mg, 4mg, 8mg, 16mg daily
versus
Placebo
patients with CHF (New York Heart Association class II or III) with impaired left ventricular function (ejection fraction <=40%) and pulmonary capillary wedge pressure >=13 mm Hgdouble blind
Follow-up duration: 12 wk
Europe, South Africa
SPICE, 2000
Candesartan, 16 mg daily
versus
Placebo
patients with chronic heart failure and left ventricular ejection fraction less than 35%, and history of discontinuing an ACE inhibitor because of intolerance double blind
Follow-up duration: 12 wk
STRETCH, 1999
Candesartan, 4 mg, 8mg, 16mg daily
versus
Placebo
Male and female patients 21 to 80 years of age with mild to moderate symptomatic CHF (NYHA class II or III)Double blind
Follow-up duration: 12 wk
Germany, Czech Republic, Slovenia.
candesartan+ACE inhibitor versus ACE inhibitor only
RESOLVD association, 1999
Candesartan, 4 mg, 8mg daily, plus enalapril, 10 mg twice daily
versus
Enalapril, 10 mg twice daily
Patients with New York Heart Association functional class NYHA II, III, or IV CHF, 6-minute walk distance (6MWD) >500 m, and ejection fraction (EF) <0.40
Follow-up duration: 43 wk
multicenter
CHARM-Added, 2003
Candesartantarget dose 32 mg once daily
versus
Placebo
patients with New York Heart Association functional class II–IV CHF and left-ventricular ejection fraction40% or lower, and who were being treated with ACE inhibitors.double blind
Follow-up duration: Median, 41 mo
26 countries
captopril versus enalapril
packer, 1986
captopril 150 mg/d
versus
enalapril 40mg/d
patient with severe chronic heart failureopen
Follow-up duration: 1-3 months
captopril versus placebo
SAVE, 1992
Captopril 12·5 mg initial dose, up to 25–50 mg three times daily
versus
placebo
patient within 3–16 days of a MI, LVEF <40%double blind
Follow-up duration: 3.5y
Barabino, 1991
captopril (37.5-75 mg/day)
versus
placebo
old patients (>75y) under treatment with digitalis and/or diureticsdouble blind
Follow-up duration: 6 months
Pfeffer, 1988
Captopril
versus
placebo
patient within 11-31 days after MI, LVEF<=45%, not in overt congestive heart failuredouble blind
Follow-up duration: 1 year
Bussmann, 1987
captopril
versus
placebo
patients with severe heart failure (NYHA classes III and IV) on treatment with digitalis and diuretics double blind
Follow-up duration: 6 months
Sogaard, 1994
Captopril 50mg daily
versus
placebo
patients with left ventricular (LV) dysfunction on day 7 after MIdouble blind
Follow-up duration: 6 months
Captopril Digoxin Multicenter Research Group, 1988
captopril
versus
placebo
patients with mild to moderate heart failuredouble blind
Sharpe, 1988
Captopril 25 mg thrice a day
versus
placebo
patients with symptomless left ventricular dysfunction (LVEF<45%) 1 week after a myocardial infarction without clinical evidence of heart failuredouble blind
Follow-up duration: 1 year
Mortarino, 1990
Captopril 25 mg bid
versus
placebo
patient with mild congestive heart failure after recent MIdouble blind
Follow-up duration: 2 months
Cilazapril-Captopril Multi-centre Group (capt vs pbo), 1995
cilazapril 1-2.5 mg once daily
versus
placebo
patients with chronic heart failure (New York Heart Association classes II-IV) double blind
Follow-up duration: 12 weeks
CMRG, 1983
captopril
versus
placebo
patients with heart failure refractory to digitalis and diuretic therapydouble blind
Follow-up duration: 12 weeks
Magnani, 1986
captopril 25 mg t.i.d.
versus
placebo
patients on digitalis treatment for chronic congestive heart failure (NYHA class II-III)double blind
Follow-up duration: 1 year
Magnani, 1990
captopril
versus
placebo
patients with congestive heart failure double blind
Munich MHFT (Kleber), 1992
captopril 25 mg twice a day
versus
placebo
patients with congestive heart failure New York Heart Association (NYHA) functional class I-III on standard treatment Double blind
Follow-up duration: 2.7y (median)
Germany
Cardiac stem cells versus control
SCIPIO, 2011
NCT00474461
Intracoronary Injection of Cardiac Stem Cells Harvested From Right Atrial Appendages
versus
Patients With Ischemic Cardiomyopathy
Cardiopoietic stem cell versus control
C CURE, 2013
NCT00810238
autologous bone marrow-derived and cardiogenically oriented mesenchymal stem cell therapy
versus
patients with heart failure of ischemic origin
CADUCEUS, 2012
NCT00893360

versus
patients with left ventricular dysfunction after myocardial infarction
carvedilol versus enalapril
CARMEN (carvedilol alone), 2004
carvedilol (target 25 mg bid)
versus
enalapril (target 10 mg bid)
patients with mild heart failureND
Follow-up duration: 18 months
carvedilol versus metoprolol
COMET, 2003
carvedilol (target dose 25 mg twice daily)
versus
metoprolol tartrate target dose 50 mg twice daily
chronic heart failure (NYHA II–IV) with a previous admission for a cardiovascular reason and ejection fraction of less than 0·35, and have been treated optimally with diuretics and angiotensinconverting enzyme inhibitors unless not tolerated.Double blind
Follow-up duration: 4.83 years
15 European countries
carvedilol versus placebo
ANZ-HeFT, 1997
carvedilol target dose 25mg twice daily
versus
placebo
chronic stable heart failure, NYHA 1-3Double blind
Follow-up duration: 19 mo (range 18-24 mo)
Australia & New Zealand
Parker, 1996
carvediloltarget dose 25 mg twice daily
versus
placebo
patients with heart failure and ejection fraction<0.35 Double blind
Follow-up duration: 6.5 mo (1 day - 15.1 mo)
US
Carvedilol versus placebo
Carvedilol U.S. Trials (elderly subgroup), 1996
Carvedilol
versus
placebo
Patients aged 65 years and older
COPERNICUS (elderly subgroup), 2001
Carvedilol
versus
placebo
Patients aged 59 years and older
carvedilol versus placebo
Metra, 1994
carvedilol
versus
placebo
NYHA 2-3, IDC
Follow-up duration: 4 mo
Olsen, 1995
carvedilol
versus
placebo
NYHA 2-4, IDC/CAD
Follow-up duration: 4 mo
Krum, 1995
carvedilol 25 mg twice daily during 14 weeks
versus
placebo
Patients with advanced heart failure(NYHA 3-4), EF <=0.35
Follow-up duration: 3.5 mo
Bristow (MOCHA), 1996
carvedilol
versus
placebo
NYHA 2-4, IDC/CADDouble blind
Follow-up duration: 6.5-8 mo
Colucci, 1996
carvedilol
versus
placebo
mild symptomatic heart failure; ejection fraction<=0.35; 6-minute walk test of 450-550m; on optimal standard therapy including ACE inhibitorsDouble blind
Follow-up duration: 213 days (0.6 years)
US
Cohn, 1997
carvedilol
versus
placebo
NYHA 3-4, IDC/CAD
Follow-up duration: <8 mo
CAPRICORN, 2001
carvedilol target dose 25mg twice daily
versus
placebo
proven acute myocardial infarction and a left-ventricular ejection fraction of <=40%Double blind
Follow-up duration: 1.3 years
17 countries
COPERNICUS, 2002
carvedilol traget dose of 25 mg twice daily
versus
placebo
patients with symptoms of heart failure at rest or on minimal exertion and with an ejection fraction <25% (but not volume-overloaded)Double blind
Follow-up duration: 10.4 months
worldwide (21 countries)
Celacade™ system versus placebo
ACCLAIM, 2008
NCT00111969
device-based non-specific immunomodulation therapy with Celacade™ system
versus
placebo
patients with NYHA functional class II-IV chronic heart failure, left ventricular (LV) systolic dysfunction, and hospitalisation for heart failure or intravenous drug therapy in an outpatient setting within the past 12 months.double blind
Follow-up duration: 10.2 months
cerivastatin versus placebo
Laufs, 2004
cerivastatin 0.4 mg
versus
placebo
patients with heart failure NYHA II-III caused by non-ischemic dilated cardiomyopathydouble blind
Follow-up duration: mean 20 weeks
cilazapril versus captopril
Cilazapril-Captopril Multi-centre Group (cila vs capt), 1995
cilazapril 1-2.5 mg once daily
versus
captopril 25-50mg three times daily
patients with chronic heart failure (New York Heart Association classes II-IV) double blind
Follow-up duration: 12 weeks
cilazapril versus placebo
Cilazapril-Captopril Multi-centre Group, 1995
cilazapril 1-2.5 mg once daily
versus
placebo
patients with chronic heart failure (New York Heart Association classes II-IV)double blind
Follow-up duration: 12 weeks
Dosseger, 1993
cilazapril titrated up to 2.5 mg/d
versus
placebo
patients with chronic heart failure (NYHA class II to IV) stabilized on digitalis and/or diureticsdouble blind
Follow-up duration: 12 weeks
Drexler, 1989
cilazapril
versus
placebo
patients with chronic heart failuredouble blind
Follow-up duration: 3 months
Combined CRT + ICD versus CRT
COMPANION (CRT+ICD vs CRT), 2004
ICD+CRT
versus
CRT
patients with advanced heart failure (NYHA III or IV) due to ischemic and non-ischemic cardiomyopathy with EF <=0.35 and QRS duration >120 ms open
Follow-up duration: 16 months
Combined CRT + ICD versus ICD alone
MIRACLE-ICD-II, 2004
ICD+CRT (and optimalmedical treatment)
versus
ICD (optimalmedical treatment)
NYHA class II heart failure patients on optimal medical therapy with a left ventricular (LV) ejection fraction <=35%, a QRS >=130 ms, and a class I indication for an ICDdouble blind
Follow-up duration: 6 months
MADIT CRT, 2009
NCT00180271
Cardiac resynchronization therapy with implantable cardioverter defibrillator
versus
implantable cardioverter defibrillator alone
patients with asymptomatic or mildly symptomatic heart failure (NYHA I/II), LEVF<=30% and QRS>=130msblinded
Follow-up duration: 2 years
United States, Europe
RAFT, 2010
NCT00251251
ICD plus CRT
versus
ICD alone
patients with New York Heart Association (NYHA) class II or III heart failure, a left ventricular ejection fraction of 30% or less, and an intrinsic QRS duration of 120 msec or more or a paced QRS duration of 200 msec or moredouble-blind
Follow-up duration: 40 months
Canada, Europe, Turkey, Australia
MIRACLE-ICD-I, 2003
ICD+CRT (plus optimal medical treatment)
versus
ICD (plus optimal medical treatment)
patients with NYHA class III or IV congestive HF despite appropriate medical managementdouble blind
Follow-up duration: 6 months
CONTAK-CD , 2003
ICD+CRT
versus
ICD (no CRT)
patients with symptomatic heart failure, intraventricular conduction delay, and malignant ventricular tachyarrhythmias open
Follow-up duration: 4.7 months
Combined CRT + ICD versus no CRT
RethinQ, 2007
NCT00132977
cardiac-resynchronization therapy ICD+CRT
versus
no cardiac-resynchronization therapy
patients with standard indication for an implantable cardioverter-defibrillator, NYHA 3, EF<35%, QRS<130ms, and evidence of mechanical dyssynchronyopen
Follow-up duration: 6 months
USA
Combined CRT + ICD versus no CRT no ICD
AMIOVIRT, 2003
ICD
versus
amiodarone as medical therapy
patients with non ischemic cardiomyopathy with EF <=0.35 and Nonsustained ventricular tachycardiaopen
Follow-up duration: 24 months
COMPANION (CRT+ICD vs MT), 2004
ICD+CRT
versus
no ICT no CRT, optimized medical therapy
patients with advanced heart failure (NYHA III or IV) due to ischemic and non-ischemic cardiomyopathy with EF <=0.35 and QRS duration >120 ms open
Follow-up duration: 16 months
continuous-flow HeartMate II versus pulsatile-flow HeartMate XVE
HeartMate II, 2009
NCT00121485
continuous-flow HeartMate II ventricular assist device
versus
pulsatile-flow HeartMate XVE ventricular assist device
patients with advanced heart failure not eligible for heart transplantationopen
Follow-up duration: 2 y
CRT versus no CRT
REVERSE, 2008
NCT00271154).
CRT
versus
"placebo"
patients with NYHA functional class I or II heart failure with a QRS >=120 ms and a LV ejection fraction <=40%double blind
Follow-up duration: 12 months
MUSTIC-SR, 2001
CRT Medtronic/ELA medical
versus
CRT off
patients with severe heart failure (New York Heart Association class III) due to chronic left ventricular systolic dysfunction, with normal sinus rhythm and a duration of the QRS interval of more than 150 msecSingle blind
Follow-up duration: 3 months
MIRACLE, 2002
CRT Medtronic
versus
CRT off
patients with moderate-to-severe symptoms of heart failure associated with an ejection fraction of 35 percent or less and a QRS interval of 130 msec Bouble blind
Follow-up duration: 6 months
PATH-CHF, 2002
CRT
versus
no CRT
patients with heart failure and ventricular conduction delayopen
Follow-up duration: 1 month
MUSTIC AF, 2002
CRT Medtronic/ELA medical
versus
CRT off
patients with NYHA class III left ventricular systolic dysfunction, chronic atrial fibrillation, slow ventricular rate necessitating permanent ventricular pacing, and a wide QRS complex (paced width >or=200 ms)Single blind
Follow-up duration: 3 months
CARE-HF, 2005
CRT medtronic
versus
no CRT
patients with NYHA class III or IV heart failure due to left ventricular systolic dysfunction and cardiac dyssynchrony open
Follow-up duration: 29.4 months
RD-CHF, 2003
CRT
versus
no CRT
patients with advanced heart failure
COMPANION (CRT vs MT), 2004
CRT guidant
versus
no CRT, optimized medical therapy
patients with advanced heart failure (NYHA III or IV) due to ischemic and non-ischemic cardiomyopathy with EF <=35% and QRS duration >120 msopen
Follow-up duration: 16 months
Garrigue, 2002
CRT
versus
no CRT
patients with chronic atrial fibrillation, severe heart failure and QRS prolongation of > or = 140 ms single blind
darbepoetin alfa versus placebo
STAMINA-HeFT (Ghali), 2008
NCT00049985
darbepoetin alfa SC every 2 weeks for 1 year (target hemoglobin, 14.0+/-1.0 g/dL).
versus
placebo
Patients with symptomatic HF, left ventricular ejection fraction < or = 40%, and hemoglobin > or = 9.0 g/dL and < or = 12.5 g/dL double blind
Follow-up duration: 27 weeks
van Veldhuisen, 2007
NCT00086086
darbepoetin alfa subcutaneously every 2 weeks for 26 weeks at a starting weight-adjusted dose of 0.75 mcg/kg or a fixed dose of 50 mcg
versus
placebo
Patients with chronic heart failure (>=3 months), left ventricular ejection fraction <= 40%, and Hb 9.0 to 12.5 g/dLdouble blind
Follow-up duration: 27 weeks
Ponikowski, 2007
NCT00117234
Subcutaneous (SC) Darbepoetin Alfa
versus
subcutaneous placebo
patients with Symptomatic Congestive Heart Failure (CHF) and Anemiadouble blind
Follow-up duration: 27 weeks
Parissis, 2008
3-month darbepoetin alpha regimen at 1.5 microg/kg every 20 days plus oral iron
versus
placebo plus oral iron
CHF patients NYHA II-III, LV ejection fraction [EF] <40%, hemoglobin level <12.5 g/dL, serum creatinine level <2.5 mg/dL
Parissis, 2009
3-month darbepoetin alfa regimen at 1.5 microg/kg every 20 days plus oral iron
versus
placebo plus oral iron
patients with CHF (LV ejection fraction [LVEF] <40%, hemoglobin <12.5 g/dl, and serum creatinine <2.5 mg/dl
Kourea, 2008
3-month darbepoietin-alpha at 1.5 microg/Kg every 20 days plus iron orally
versus
placebo plus iron orally
CHF patients NYHA II-III; left ventricular ejection fraction <40%; hemoglobin<12.5 g/dl; serum creatinine<2.5 mg/dldouble blind
digoxin versus placebo
Lee, 1982
digoxin titrated to mean serum level of 1.15 ng/mL, mean dig dosage .435 mg/day
versus
placebo
outpatients without atrial fibrillationdouble blind
Follow-up duration: 53 days
Taggart, 1983
digoxin (mean plasma dig level 1.2 ng/mL)
versus
placebo (digoxin withdrawal)
patients with sinus rhythm who had a previous history of frank heart failure double blind
Follow-up duration: 3 months
Fleg, 1982
digoxin titrated to serum level of 1.0 to 2.0 ng/mL
versus
placebo
patients with chronic clinically compensated congestive heart failure and normal sinus rhythmdobl eblind
Follow-up duration: 3 months
Captopril-Digoxin Multicenter Research Group (CDMRG), 1988
digoxin of .125-.375 mg/day titrated to serum levels of .7-2.5 ng/mL
versus
placebo (digoxin withdrawal)
patients with mild to moderate heart failure.double blind
Follow-up duration: 6 months
German and Austrian Xamoterol Study, 1988
digoxin .125 mg twice dayly (mean plasma dig level .87 ng/mL)
versus
placebo
patients aged 29-80 with mild to moderate heart failure double blind
Follow-up duration: 3 months
Guyatt, 1988
digoxin titrated to serum level of 1.54– 2.56 nmol/L (1.2–2.0 ng/mL), mean dig dosage 0.391 mg/day
versus
placebo
congestive heart failure patients in sinus rhythmdouble blind
Follow-up duration: 7 weeks
DiBianco, 1989
digoxin .125-.5 mg/ day
versus
placebo
patients in sinus rhythm with moderately severe heart failure double blind
Follow-up duration: 3 months
Pugh, 1989
digoxin (patient’s “usual dose” )
versus
placebo (digoxin withdrawal)
patients with stable heart failure in sinus rhythm and plasma digoxin concentrations over 0.8 ng/ml double blind
Follow-up duration: 2 months
Blackwood, 1990
digoxin .25 mg/day
versus
placebo
patients with heart failuredouble blind
Follow-up duration: 3 months
Radiance, 1993
digoxin titrated to serum level of 1.2 ng/mL (mean dig dosage .38 mg/day)
versus
placebo (digoxin withdrawal)
patients with New York Heart Association class II or III heart failure and left ventricular ejection fractions of 35 percent or less in normal sinus rhythm who were clinically stable while receiving digoxin, diuretics, and an angiotensin-converting-enzyme inhibitor (captopril or enalapril)double blind
Follow-up duration: 3 months
Proved, 1993
digoxin titrated to serum level of 1.2 ng/mL (median dig dosage .375 mg/day)
versus
placebo (digoxin withdrawal)
patients with chronic, stable mild to moderate heart failuredouble blind
Follow-up duration: 3 months
DIMT, 1993
digoxin .25 mg/day (mean plasma level .94 ng/mL)
versus
placebo
patients with mild to moderate chronic heart failure double blind
Follow-up duration: 6 months
Digitalis Investigation Group (DIG), 1997
NCT00000476
digoxin dosage at investigators’ discretion (median baseline dosage in main trial of .25 mg/day)
versus
placebo
patients with left ventricular ejection fractions of 0.45 or less and normal sinus rhythmDouble blind
Follow-up duration: 37 mo (mean)
US, Canada
diltiazem versus placebo
DiDi, 1996
diltiazem 60mg three times daily
versus
placebo
idiopathic dilated cardiomyopathy and LVEF<0.50Double blind
Follow-up duration: 24 months
germany
Diltiazem versus placebo
Liao , 1998
diltiazem 30mg twice daily
versus
control (vitamin B1 30mg twice daily)
patients with dilated cardiomyopathySimple aveugle
Follow-up duration: 6 months
China
diuretic agents versus placebo
Burr, 1977
diuretic agents
versus
placebo (withdrawals)
elderly patients taking long-term diureticsdouble blind
Follow-up duration: 12 weeks
dronedarone versus placebo
ANDROMEDA, 2008
NCT00543699
dronedarone 400mg twice daily
versus
placebo
patients hospitalized with symptomatic heart failure and severe left ventricular systolic dysfunctiondouble blind
Follow-up duration: median 2 months
enalapril versus control
Enalapril CHF investigators, 1987

versus
Rucinska-a (enalapril), 1991

versus
Rucinska-b (enalapril), 1991

versus
enalapril versus enalapril
NETWORK (2.5 bid vs 10 bid), 1998
enalapril 2.5 mg twice daily
versus
enalapril 10 mg twice daily
patients with NYHA II-IV heart failure double blind
Follow-up duration: 6 months
UK
NETWORK (5 bid vs 10 bid), 1998
enalapril 5 mg twice daily
versus
enalapril 10 mg twice daily
patients with NYHA II-IV heart failure double blind
Follow-up duration: 6 months
UK
enalapril versus hydralazine+ISDN
V-HeFT II, 1991
enalapril 20mg daily
versus
hydralazine 300 mg plus isosorbide dinitrate 160 mg daily
men with chronic congestive heart failure and cardiac dilatation (CT ratio>0.55) or LVEF <45% in association with reduced exercise tolerance and diuretic therapy double blind
Follow-up duration: 2.5y (range 0.5-5.7y)
enalapril versus placebo
CASSIS (enalapril), 1995
enalapril 5-10mg daily
versus
placebo
patients with chronic congestive heart failure of NYHA classes II-IVdouble blind
Follow-up duration: 12 weeks
Chrysant, 1985
enalapril
versus
placebo
patients with congestive heart failure (CHF), New York Heart Association class II-IIIdouble blind
Follow-up duration: 14 weeks
Cleland, 1985
enalapril titrated up to 40mg once daily
versus
placebo
patients with New York Heart Association functional class II to IV heart failure who were clinically stable on digoxin and diuretic therapydouble blind
Follow-up duration: 8 weeks
CONSENSUS, 1987
enalapril (2.5 to 40 mg per day)
versus
placebo
severe congestive heart failure (New York Heart Association [NYHA] functional class IV)double blind
Follow-up duration: 188 days
Finland, Sweden, Norway
Dickstein, 1991
enalapril
versus
placebo
men with symptomatic heart failure (functional class II or III) and documented myocardial infarction greater than 6 months previously double blind
Follow-up duration: 48 weeks
McGrath, 1985
enalapril
versus
placebo
patients with chronic congestive cardiac failure double blind
Follow-up duration: 12 week
Sharpe, 1984
enalapril 5mg twice day
versus
placebo
patients with New York Heart Association functional class II to III heart failure who were clinically stable on digoxin and diuretic therapydouble blind
Follow-up duration: 3 months
SOLVD prevention, 1992
NCT00000516
Enalapril initial dose 2·5 or 5 mg twice daily up to 10 mg twice daily
versus
placebo
MI >1 month,No treatment for CHF, LVEF <=35%double blind
Follow-up duration: 3.1 y
SOLVD treatment, 1991
NCT00000516
Enalapril initial dose 2·5 or 5 mg twice daily up to 10 mg twice daily
versus
placebo
MI >1 month,Congestive HF, LVEF <=35%Double blind
Follow-up duration: 3.5 y
enoxaparin versus UFH
THE-PRINCE (Kleber), 2003
enoxaparin 40mg once daily for 10+/-2 days
versus
UFH 5000 IU 3 times daily for 10+/-2 days
patients hospitalized for severe respiratory disease or heart failure (NYHA III, IV)open
germany
Enoximone versus placebo
Cowley, 1994
Enoximone 300mg/d
versus
placebo
NYHA III,IVdouble blind
Follow-up duration: 12 months
enoximone versus placebo
EMOTE, 2007
enoximone
versus
placebo
patients with ultra-advanced heart failure requiring IV inotropic therapydouble blind
Follow-up duration: 26 weeks
US
Enoximone versus placebo
EMTG, 1990
Enoximone <450 mg/d
versus
placebo
NYHA II, IIIdouble blind
Follow-up duration: 4 months
ESG, 2000
Enoximone 75-150 mg/d
versus
placebo
NYHA II, IIIdouble blind
Follow-up duration: 3 months
enoximone versus placebo
ESSENTIAL (I and II), 2009
NCT00051285
enoximone titrated to 50 mg three times daily
versus
placebo
Patients with New York Heart Association class III–IV HF symptoms, left ventricular ejection fraction 30%, and one hospitalization or two ambulatory visits for worsening HF in the previous yeardouble blind
Follow-up duration: 16.6 mo (median)
Europe and North andSouth America
Enoximone versus placebo
Lardoux, 1987
Enoximone 150, 300mg/d
versus
placebo
NYHA NAdouble blind
Follow-up duration: 3 months
WESG, 1991
Enoximone 150, 300 mg/d
versus
placebo
NYHA II, IIIdouble blind
Follow-up duration: 3 months
eplerenone versus placebo
EMPHASIS-HF, 2010
NCT00232180
eplerenone
versus
placebo
patients with New York Heart Association class II heart failure and an ejection fraction of no more than 35%double blind
Follow-up duration: 21 months
29 countries
EPHESUS, 2003
eplerenone 25 mg per day initially, titrated to amaximum of 50 mg per day
versus
placebo
patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failureDouble blind
Follow-up duration: 16 mo (mean, range 0 to 33)
37 countries
epoprostenol versus standard care
FIRST, 1997
epoprostenol infusion
versus
standard care
Patients with class IIIB/IV congestive heart failure and decreased left ventricular ejection fractionNA
Follow-up duration: 3 and 6 months
eprosartan+ACE inhibitor versus ACE inhibitor only
ADEPT, 2001
Eprosartan, 400 to 800 mg twice daily
versus
Placebo
patients with stable New York Heart Association class II-IV CHF receiving ACE inhibitor therapydouble blind
Follow-up duration: 8 wk
Exercise training versus control
Dubach et al, 1997
Supervised walking, two hours daily; supervised cycling 40minutes four days a week
versus
control
patients with chronic heart failure open
Follow-up duration: 0.7 y
Switzerland
Giannuzzi et al, 1997
Supervised cycling, 30 minutesthree days a week for two months, then home based 30 minutes for three days a week and walking for 30 minutes
versus
control
patients with <40% ejection fraction after a first Q-wave myocardial infarction open
Follow-up duration: 0.6 y
Italy
Belardinelli et al, 1999
Supervised cycling, 60 minutes three days a week for eightweeks, then two days a week
versus
no exercise
patients with CHF open
Follow-up duration: 3.1 y
Italy
Hambrecht et al, 1995
Supervised and home based walking, calisthenics, cycling40-60 minutes a day
versus
physically inactive control group
patients with chronic heart failure open
Follow-up duration: 0.4 y
Germany
ExTraMATCH, 2004

versus
Kiilavuori et al, 2000
Supervised cycling 30 minutes three days a week for three months, then home basedtraining (walking, cycling,rowing, and swimming)
versus
control
patients with stable NYHA class II-III CHFopen
Follow-up duration: 6.3 y
Finland
McKelvie et al, 2002
Supervised aerobic (cycling,treadmill, arm) and resistance training 30 minutes three days a week for three months, then home based aerobic training three days a week
versus
usual care
patients in NYHA class I to III, with ejection fraction <40% and 6-minute walk distance <500 meterssingle blind
Follow-up duration: 1.5 y
Canada
Zanelli et al, 1997
Supervised aerobic (cycling,treadmill, arm) and resistance training 30 minutes two days a week and home based cycling three days a week for two months, then only home based aerobic training five days a week
versus

Follow-up duration: 0.8 y
Italy
Wielenga et al, 1999
Supervised cycling, walking,ball game 30 minutes threedays a week for eight weeks, then two days a week
versus
control
patients with chronic heart failure NYHA II-III open
Follow-up duration: 3.9 y
Netherlands
Willenheimer et al, 1998
Supervised interval cyclingtraining (90 second exercise and 30 second rest) for 15-45 minutes two days a weekc
versus
control
patients with stable mild-to-moderate heart failure open
Follow-up duration: 4.4 y
Sweden
felodipine versus enalapril
Dunselman, 1990
felodipine 10 mg b.i.d.
versus
enalapril 10 mg b.i.d.
patients with congestive heart failure due to ischaemic heart disease and NYHA class IIIDouble blind
Follow-up duration: 4 months
De Vries, 1995
felodipine 2.5mg twice daily
versus
enalapril 2.5mg twice daily
patients NYHA class II-III with left ventricular ejection fraction <0.4, symptoms of CHD despite therapy with diuretics and digoxinDouble blind
Follow-up duration: 4 months
the Netherlands
felodipine versus placebo
VHeFT III, 1997
felodipine 5mg twice daily
versus
placebo
male patient over 18 years with heart failureDouble blind
Follow-up duration: mean 18mo (range 3-39 mo)
US
Kassis, 1987
felodipine 10 mg twice daily
versus
placebo
patients on conventional therapy for severe CHFDouble blind
Follow-up duration: 3 weeks
Denmark
Kassis, 1990
felopidine 10 mg BID
versus
placebo
severe congestive heart failure (NYHA class III)Double blind
Follow-up duration: 6 months
Denmark
Felodipine versus placebo
Littler, 1995
felodipine extended release 2.5-10mg twice daily (in addition to existing background medication) for 12 weeks
versus
placebo
patients with NYHA class II-III stable congestive heart failure despite treatment with ACE inhibitors, diuretic and digoxin or any combinaison of these drugsDouble blind
Follow-up duration: 3 months
UK
ferric carboxymaltose versus placebo
FAIR-HF (Anker), 2009
ferric carboxymaltose
versus
placebo
patients with systolic heart failure and iron deficiency double blind
Follow-up duration: 24 weeks
11 countries
Flosequinan versus placebo
REFLECT II, 1991
Flosequinan 100, 150 mg/d
versus
NYHA II-IVdouble blind
Follow-up duration: 3 months
Cowley, 1993
Flosequinan 125mg/d
versus
placebo
NYHA II, IIIdouble blind
Follow-up duration: 4 months
FACET, 1993
Flosequinan 100 and 150 mg/d
versus
placebo
NYHA II, IIIdouble blind
Follow-up duration: 4 months
REFLECT, 1993
Flosequinan 100mg/d
versus
placebo
NYHA II,IIIdouble blind
Follow-up duration: 3 months
fosinopril versus placebo
Brown, 1995
fosinopril 10 or 20 mg/day
versus
placebo
patients with chronic congestive heart failure (NYHA II-III) not taking digitalisdouble blind
Follow-up duration: 24 weeks
FEST (Erhardt), 1996
fosinopril 40 mg once daily titrated
versus
placebo
patients with mild to moderately severe heart failure (NYHA II-III)double blind
Follow-up duration: 12 weeks
frusemide plus amiloride versus captopril
Richardson, 1987
frusemide plus amiloride
versus
captopril
patients who had previously been treated with diureticsdouble blind
Follow-up duration: 8 weeks
furosemide versus captopril
Boccanelli, 1986
furosemide 25 to 100 mg od
versus
captopril 12.5 to 50 mg bid +furosemide 25mg od
patients with moderate congestive heart failure not completely controlled on digoxin (0.25 mg o.d.) and frusemide (25 mg o.d.), double blind
Follow-up duration: 13 weeks
Cowley, 1986
furosemide (increased doses of frusemide)
versus
captopril (addition)
patients with moderate heart failure who still had symptoms despite 40 mg frusemide dailydouble blind
furosemide versus placebo
Mathur, 1984
furosemide hydrochlorotiazide
versus
placebo
patient with pulmonary heart disease due to severe chronic airflow obstruction and clinical features of congestive heart failure during respiratory failuredouble blind
furosemide + spironolactone versus prenalterol
Dalhstrom, 1986
intensified treatment with diuretics (furosemide- spironolactone)
versus
prenalterol 100-200 mg daily in addition to their basal treatment
patients with severe chronic congestive heart failure (CHF) due to ischaemic heart disease treated with digitalis and diuretics double blind
Follow-up duration: 12 weeks
gene therapy versus placebo
CUPID, 2011
SERCA2a gene therapy
versus
placebo
patients NYHA class 3-4 heart failure and an LVEF <35%double-blind
Follow-up duration: 6 months
US
hydralazine versus control
Chatterjee, 1980
oral hydralazine
versus
NA
patients with chronic CHF
hydralazine versus placebo
Franciosa, 1982
hydralazine 200 mg daily
versus
placebo
patients with class III and IV symptoms while they were taking digitalis and diureticsdouble blind
Follow-up duration: 20 weeks
Conradson , 1984
hydralazine
versus
placebo
patients with chronic congestive heart failure (NYHA class III)
Follow-up duration: 1 year
Magorien , 1984
hydralazine 100 mg orally every eight hours
versus
placebo
patients with idiopathic dilated cardiomyopathydouble blind
hydralazine-ISDN versus placebo
VHeFT I (hydralazine ISDN), 1986
hydralazine 300mg/d ISDN 160mg/d
versus
placebo
patienst with chronic congestive heart failure and cardiac dilatation (CT ratio>0.55) or LVEF <45% in association with reduced exercise tolerance double blind
Follow-up duration: 2.3 y (range 0.5-5.7 years)
hydrochlorothiazide versus benazepril
Nordrehaug, 1992
hydrochlorothiazide 50 mg daily
versus
benazepril 20 mg daily
patients with symptomatic (NYHA functional class 2) mild heart failuredouble blind
Follow-up duration: 8 weeks
hydrochlorothiazide+triamterene versus digoxin
Sievert, 1989
hydrochlorothiazide+triamterene
versus
digoxin
patients in heart failure and sinus rhythm double blind
Follow-up duration: 5 weeks
ibesartan versus placebo
I-PRESERVE (McMurray), 2008
NCT00095238
ibersatan 300mg daily
versus
placebo
patients with NYHA II, III, or IV heart failure and an ejection fraction of at least 45%double blind
Follow-up duration: 49.5 months
Western Europe, Eastern Europe, North America, South America, South Africa, and Australia
ibopamine versus placebo
PRIME II, 1997
oral ibopamine 100 mg three times daily
versus
placebo
patients with heart failure NYHA III-IVdouble blind
Follow-up duration: mean 11.4 months
ICD versus no ICD
MADIT, 1996
ICD
versus
anti arrhythmic drugs as conventional therapy
patients with MI >=3 wk before entry and EF <=0.35 and Asymptomatic unsustained VT unrelated to an acute MI with inducible VT not suppressed after iv procainamideopen
Follow-up duration: 27 months
MADIT-II, 2002
implantable cardiac defibrillator
versus
no ICD, optimized medical therapy
patients with a prior myocardial infarction and EF<=0.30open
Follow-up duration: 20 months
CASH, 2000
ICD
versus
antiarrhythmic agents (amiodarone and metoprolol)
secondary prevention: survivors of cardiac arrest secondary to documented ventricular arrhythmiasopen
Follow-up duration: 57 months
CAT, 2002
ICD
versus
no iCD, conventional therapy
patients with recent onset nonischemic cardiomyopathy withEF <=0.30open
Follow-up duration: 66 months
DEFINITE, 2004
ICD
versus
no ICD, standard medical therapy
patients with non ischemic cardiomyopathy with EF <0.36 and Nonsustained ventricular tachycardia or frequent premature ventricular complexesopen
Follow-up duration: 29 months
SCD-HeFT (ICD vs placebo), 2005
NCT00000609
ICD
versus
optimized medical therapy
patients with ischemic and nonischemic cardiomyopathy withEF<=0.35open
Follow-up duration: 45.5 months
AVID, 1997
NCT00000531
ICD
versus
class III antiarrhythmic drugs, primarily amiodarone
secondary prevention: patients who had been resuscitated from near-fatal ventricular fibrillation or who had undergone cardioversion from sustained ventricular tachycardiaopen
Follow-up duration: 18.2 months
CIDS, 2000
ICD
versus
amiodarone
secondary prevention: patients with resuscitated VF or VT or with unmonitored syncope
Follow-up duration: 36 months
CABG-patch, 1997
NCT00000540
ICD
versus
control
patients undergoing CABG with EF <=0.35 and Abnormal signal-averaged electrocardiogramopen
Follow-up duration: 32 months
DINAMIT, 2004
implantable cardioverter defibrillator
versus
no ICD, optimized medical therapy
patients within 6–40 days of myocardial infarct ischemic with EF<=0.35 and cardiac autonomic modulation (depressed heart rate variability or increased mean 24-hour heart rate)open
Follow-up duration: 30 months
MUSIT, 1999
ICD or drugs as indicated by electrophysiologic testing
versus
no antiarrhythmic therapy
patients with ischemic cardiomyopathy with EF<=0.40 and Inducible, sustained ventricular tachyarrhythmiasopen
Follow-up duration: median 39 months
SCD-HeFT (ICD vs amiodarone), 2005
NCT00000609
ICD
versus
optimized medical therapy with amiodarone
patients with ischemic and nonischemic cardiomyopathy withEF<=0.35open
Follow-up duration: 45.5 months
Imazodan versus placebo
IRG, 1991
Imazodan 4,10, 20 mg/d
versus
placebo
NYHA III,IVdouble blind
Follow-up duration: 3 months
Indolidan versus placebo
Dies, 1989
Indolidan dose NA
versus
placebo
NYHA II,IIIdouble blind
Follow-up duration: 3 months
irbesartan+ACE inhibitor versus ACE inhibitor only
Tonkon et al., 2000
Irbesartan, 150 mg daily (plus ACE inhibitor)
versus
Placebo (plus ACE inhibitor)
patients with heart failure (New York Heart Association functional class II and III) and left ventricular ejection fraction (LVEF) < or = 40% received stable doses of ACE inhibitors and diureticsdouble blind
Follow-up duration: 12 wk
isosorbide dinitrate versus placebo
NICE (Lewis), 1999
isosorbide-5-mononitrate 50 mg once daily
versus
placebo
patients (NYHA Class 2-3) treated for heart failure, all receiving captopril and most also furosemide
Follow-up duration: 12 weeks
Franciosa , 1978
isosorbide dinitrate
versus
placebo
double blind
isradipine versus placebo
Van den Toren, 1996
isradipine up to 5mg 3 times daily
versus
placebo
patients with congestive heart failure due to ischaemic heart disease, NYHA class II-III, FE<40%Double blind
Follow-up duration: 3 months
The NetherlanA
ivabradine versus placebo
SHIFT, 2010
ISRCTN70429960
ivabradine
versus
placebo
patients with NYHA class 2-4 heart failure, an LVEF <35%, a resting heart rate >70 bpm, and a heart-failure hospitalization within the previous year double-blind
Follow-up duration: 23 months
37 countries
ivabradine 15mg versus placebo
BEAUTIFUL, 2008
NCT00143507
ivabradine target dose of 7·5 mg twice a day
versus
placebo
patients with coronary artery disease and left-ventricular systolic dysfunction (LVEF <=40%) double blind
Follow-up duration: 19 months (range 16-24)
33 countries
ixmyelocel-T versus control
Catheter-DCM, 2014
NCT01020968
ixmyelocel-T: an expanded, autologous multi-cellular therapy
versus
patients with dilated cardiomyopathy
IMPACT-DCM, 2014
NCT00765518
ixmyelocel-T: an expanded, autologous multi-cellular therapy,
versus
patients with dilated cardiomyopathy
ixmyelocel-T versus placebo
ixCELL-DCM, 2016
NCT01670981
ixmyelocel-T
versus
placebo
patients with New York Heart Association class III or IV symptomatic heart failure due to ischaemic dilated cardiomyopathy, who had left ventricular ejection fraction 35% or less, an automatic implantable cardioverter defibrillator, and who were ineligible for revascularisation procedures
lisinopril versus control
Giles, 1990

versus
Rucinska-c (lisinopril), 1000

versus
Zwehl, 1990

versus
lisinopril versus lisinopril
ATLAS, 1999
lisinopril low dose 2.5-5 mg daily
versus
lisnopril high dose 32.5-35 mg daily
patients with New York Heart Association class II to IV heart failure and an ejection fraction <=30%double blind
Follow-up duration: 39 to 58 months
19 countries
lisinopril versus placebo
Gilbert, 1993
lisinopril
versus
placebo
subjects with heart failure double blind
Follow-up duration: 12 weeks
International Study Group (Lewis), 1989
lisnopril titrated up to 10mg daily
versus
placebo
patients with congestive heart failure NYHA II-IV double blind
Follow-up duration: 12 weeks
New Zealand
losartan versus captopril
ELITE, 1997
Losartan titrated to 50 mg once daily
versus
Captopril,titratedto 50 mg three times daily
ACE inhibitor naive patients (aged 65 years or more) with New York HeartAssociation (NYHA) class II–IV heart failure and ejection fractions of 40% or lessDouble blind
Follow-up duration: 48 wk
United States, Europe and South America
ELITE II, 2000
Losartan, target dose 50 mg daily
versus
Captopril, target dose 50 mg 3 times daily
patients aged 60 years or older with New York Heart Association class II–IV heart failure and ejection fraction of 40% or less.Double blind
Follow-up duration: median 1.5y
46 countries
losartan versus enalapril
Losartan phase II S, 1996
losartan 50 or 25 mg/d
versus
enalapril 10mg twice daily
patient with heart failuredouble blind
Follow-up duration: 8 weeks
losartan phase II US, 1996
losartan 25 and 50 mg/d
versus
enalapril 10mg twice daily
patients with heart failuredouble blind
Follow-up duration: 12 weeks
Dickstein et al., 1995
Losartan, 25 mg, 50mg daily
versus
Enalapril, 10 mg twice daily
patients with moderate or severe chronic heart failure in New York Heart Association functional class III or IV and an ejection fraction < or = 35%double blind
Follow-up duration: 8 wk
Lang et al., 1997
Losartan titrated to 25 mg ou 50 mg daily
versus
Enalapril, titrated to 10 mg twice daily
patients with congestive heart failure (New York Heart Association functionalclasses II to IV) and left ventricular ejection fraction <= 45%previously treated with stable doses of ACE inhibitors and diureticagents, with or without concurrent digitalis and othervasodilatorsDouble blind
Follow-up duration: 12 wk
US, Canada
losartan versus placebo
Losartan Phase III U.S., 1995
Losartan, 50 mg daily
versus
Placebo
patients with heart failure who had never received ACE inibitors or who had discontinued ACE inhibitors double blind
Follow-up duration: 12 wk
Losartan Phase III International, 1996
Losartan, 50 mg daily
versus
Placebo
patients with heart failure who had never received ACE inibitors or who had discontinued ACE inhibitors double blind
Follow-up duration: 12 wk
losartan 150mg versus losartan 50mg
HEAAL, 2009
NCT00090259
losartan 150mg daily
versus
losartan 50 mg daily
patients with systolic heart failure who couldn't tolerate ACE inhibitorsdouble blind
Follow-up duration: 4.7 y (median)
30 countries
losartan+ACE inhibitor versus ACE inhibitor only
Hamroff et al., 1999
Losartan, 50 mg daily (plus ACE inhibitor)
versus
Placebo (plus ACE inhibitor)
patients with severe congestive heart failure (NYHA III-IV) despite treatment with maximally recommended or tolerated doses of ACE inhibitorsdouble blind
Follow-up duration: 6 mo
Mesenchymal stem cells versus allogeneic mesenchymal stem cells
POSEIDON, 2012
NCT01087996
allogeneic MSCs
versus
autologous bone marrow–derived mesenchymal stem cells delivered by transendocardial injection
patients with LV dysfunction due to ICM
metoprolol versus placebo
Engelmeier, 1985
metoprolol
versus
placebo
NYHA 2-4, IDC
Follow-up duration: 12 mo
Metoprolol versus placebo
BEST (elderly subgroup), 2001
Metoprolol
versus
placebo
Upper tertile age
metoprolol versus placebo
MDC (Waagstein), 1993
metoprolol target dose 100-150 mg daily (dose divided into two or three per day)
versus
placebo
patient with heart failure due to idiopathic dilated cardiomyopathy (NYHA 1-3) and EF<40%Double blind
Follow-up duration: 18 months
Europe, North America
Fisher, 1994
metoprolol
versus
placebo
NYHA 3-4, CAD
Follow-up duration: 6 mo
Eichhorn, 1994
metoprolol
versus
placebo
NYHA 2-3, IDC
Follow-up duration: 3 mo
MERIT-HF, 1999
metoprolol CR/XL at target dose of 200 mg once daily
versus
placebo
patients with chronic heart failure in New York Heart Association (NYHA) functional class II–IV and with ejection fraction of 0·40 or less, stabilised with optimum standard therapyDouble blind
Follow-up duration: 1 y
USA and Europe
RESOLVD, 2000
metoprolol CR 200 mg/d
versus
placebo
CHF of mixed causes, patients with symptomatic CHF(NYHA II to IV), a 6-minute walk distance of <500 m, and an LV ejection fraction (EF) of<40%Double aveugle
Follow-up duration: 6 mo
mibefradil versus placebo
MACH 1, 2000
mibefradil titrated up to100mg daily
versus
placebo
Patients with moderate to severe congestive heart failure (NYHA class II to IV and left ventricular fraction ,35%).pjDouble aveugle
Follow-up duration: 1.6 years
US, Canada, Europe and Israel
Milrinone versus placebo
MMTG, 1989
Milrinone <40mg/d
versus
placebo
NYHA II-IVdouble blind
Follow-up duration: 3 months
PROMISE, 1991
Milrinone 40mg/d
versus
placebo
NYHA III,IVdouble blind
Follow-up duration: 20 months
myoblasts versus control
CAuSMIC, 2005
3-dimensional guided catheter-based delivery of autologous skeletal myoblasts
versus
control
patients with previous myocardial infarction and heart failure, New York Heart Association (NYHA) functional class II to IV
Follow-up duration: 12 mo
SEISMIC, 2011
percutaneous intramyocardial transplantation of autologous skeletal myoblasts
versus
control
Patienst with heart failure patients with implanted cardioverter-defibrillators
Follow-up duration: 6 mo
myoblasts versus placebo
MAGIC, 2001
autologous skeletal myoblasts into the postinfarction scar during coronary artery bypass grafting of remote myocardial areas
versus
placebo
patient with severe ischaemic heart failure
Follow-up duration: 6 mo
MARVEL, 2011
NCT00526253
image-guided, catheter-based intramyocardial injection of placebo or myoblasts (400 or 800 million)
versus
placebo
patients with class II to IV HF and ejection fraction <35%
Follow-up duration: 6 mo
Nebivolol versus placebo
Lechat, 1991
nebivolol 5mg/d
versus
placebo
NYHA 3-4Double aveugle
Follow-up duration: 1.5 month
France
Wisenbaugh, 1993
nebivolol
versus
placebo
patients with dilated idiopathic or ischemic cardiomyopathy (ejection fraction 0.15 to 0.40) in stable NYHA class II or III double blind
Follow-up duration: 3 mo
nebivolol versus placebo
SENIORS, 2005
nebivolol (titrated from 1.25 mg once daily to 10 mg once daily)
versus
placebo
patients aged 70 years with a history of heart failure (hospital admission for heart failure within the previous year or known ejection fraction 35%),Double blind
Follow-up duration: 21 months
Europe
nesiritide versus control
NSGET (comparative trial), 2000
nesiritide(0.015 and 0.030 microg/kg/min
versus
usual care
acutely decompensated heart failure requiring invasive monitoring open
Follow-up duration: <5 days
US
nesiritide versus dobutamine
PRECEDENT, 2002
NCT00270400
nesiritide(0.015 or 0.03 microg/kg/min)
versus
Dobutamine (> or =5 microg/kg/min)
Symptomatic, Decompensated CHFopen
nesiritide versus nitroglycerin
VMAC (24h), 2002
NCT00083772
nesiritideinfusion for 24 hours
versus
nitroglycerin
acutely decompensated heart failure requiring hospitalization
nesiritide versus placebo
ASCEND-HF, 2011
NCT00475852
intravenous nesiritide for 24 hours to 7 days on top of standard therapy
versus
matching placebo
Patients hospitalized for heart failure (within 24 hours of hospitalization and institution of acute IV therapy for ADHF)double-blind
Follow-up duration: 30 days
North America, Europe, Latin America, Asia-Pacific region
BNP-CARDS, 2007
NCT00186329
nesiritide as a 0.01-µg/kg/min infusion for 48 hours
versus
placebo
acute decompensated heart failure with moderate to severe renal insufficiency Double blind
Follow-up duration: 7 days
US
FUSION 2, 2008
NCT00091520
nesiritide (2 µg/kg bolus plus 0.01 µg/kg-per-minute infusion for four to six hours)
versus
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/mindouble-blind
Follow-up duration: 12 weeks
NSGET (efficacy trial), 2000
nesiritide(0.015 and 0.030 microg/kg/min
versus
placebo
acutely decompensated heart failure requiring invasive monitoring
PROACTION, 2003
nesiritidefor at least 12h
versus
placebo
patients presenting to the ED with acutely decompensated HF and dyspnea at rest or with minimal activitydouble-blind
Follow-up duration: 30 days
USA
VMAC (intravenous neseritide), 2002
NCT00083772
intravenous nesiritidefor 3 hours
versus
placebo
acutely decompensated heart failure requiring hospitalization double-blind
USA
nesiritide versus standard care
FUSION 1, 2004
NCT00270361
nesiritide 0.005 microg/kg/min or 0.010 microg/kg/min once weekly
versus
standard care
outpatient with co-morbid advanced heart failure and renal insufficiency open
Follow-up duration: 12 weeks
nicardipine versus control
Gheorghiade, 1991
nicardipine
versus
CHD multiple cause, NYHA class IIIDouble blind
Follow-up duration: 4 months
Abrams, 1993
nicardipine
versus
CHD multiple cause, NYHA class III-IVDouble blind
Follow-up duration: 4 months
nisoldipine versus captopril
Schofer, 1990
nisoldipine (2 X 10 mg)
versus
captopril (3 X 25 mg)
patients with congestive heart failure due to ischaemic heart disease, NYHA class II-IIIDouble blind
Follow-up duration: 3 months
nisoldipine versus placebo
Rousseau, 1994
nisoldipine 20 mg once daily
versus
placebo
patients with congestive heart failure due to ischaemic heart disease, NYHA class IIDouble blind
Follow-up duration: 2 months
Nisoldipine versus placebo
Gaudron, 1996
Nisoldipine
versus
placebo
patients with congestive heart failure due to ischaemic heart disease, NYHA class II, FE<=45%
Follow-up duration: 18 months
omapatrilat versus enalapril
OVERTURE, 2002
omapatrilat 40 mg once dailyitm
versus
enalapril 10 mg twice daily
patients with NYHA II-IV heart failuredouble blind
Follow-up duration: 14.5 months
42 countries
omapatrilat versus lisinopril
IMPRESS, 2000
omapatrilat target dose 40 mg daily
versus
lisinopril target dose 20mg daily
patients with NTHA II-IV congestive heart failure, LEVF <=40%, and receiving ACE inhibitordouble blind
Follow-up duration: 12 weeks (24 weeks)
USA, canada
perindopril versus placebo
Lechat, 1993
perindopril, 2 mg once daily
versus
placebo
patients with grade II or III New York Heart Association chronic congestive heart failure on baseline diuretic therapy double blind
Follow-up duration: 3-month
PEP CHF, 2006
perindopril, 4 mg/day
versus
placebo
patients aged >=70 years with a diagnosis of heart failure, treated with diuretics and an echocardiogram suggesting diastolic dysfunction and excluding substantial LV systolic dysfunction or valve diseasedouble blind
Follow-up duration: 26.2 months (range 12-54.2m)
Europe
Pimobendan versus placebo
Bergler-Klein, 1992
Pimobendan 10mg/day
versus
placebo
NYHA II, IIIdouble blind
Follow-up duration: 6 months
PMRG, 1992
Pimobendan 2.5, 5, 10 mg/d
versus
placebo
NYHA III,IVdouble blind
Follow-up duration: 3 months
EPOCH, 2002
Pimobendan 2.5 to 5mg/d
versus
placebo
NYHA II,IIIdouble blind
Follow-up duration: 12 months
PICO, 1996
Pimobendan 2.5, 5 mg/d
versus
placebo
NYHA II, IIIdouble blind
Follow-up duration: 6 months
piretanide versus digoxin
Haerer, 1989
piretanide
versus
digoxin
double blind
piretanide versus placebo
Sherman, 1986
piretanide
versus
placebo
patients with mild to moderately severe congestive heart failuredouble blind
Follow-up duration: 4 weeks
placebo (diuretics withdrawal) versus various diuretics
Myers (copie de 7314), 1982
placebo (diuretics withdrawal)
versus
various diuretics
elderly not receiving concurrent digoxin therapy double blind
Follow-up duration: 52 weeks
prazosin versus placebo
VHeFT I (prazosin), 1986
hydralazine 300mg/d ISDN 160mg/d , prazosin 2.5mg four times daily
versus
placebo
men with chronic congestive heart failure and cardiac dilatation (CT ratio>0.55) or LVEF <45% in association with reduced exercise tolerance double blind
Follow-up duration: 2.3 y (range 0.5-5.7 years)
Colucci, 1980
prazosin
versus
placebo
Markham, 1983
prazosin, 20 mg/day,
versus
patients with congestive heart failure receiving a stable dose of digitalis and diuretics double blind
Follow-up duration: 6 months
Higginbotham, 1983
prazosin
versus
placebo
pulsatile-flow versus medical treatment
REMATCH, 2001
left ventricular assist device
versus
optimal medical management
patients with end-stage heart failure who were ineligible for cardiac transplantation open
Follow-up duration: >1 y
ramipril versus control
Swedberg, 1991

versus
ramipril versus placebo
AIRE, 1993
Ramipril 2·5 mg twice daily initial dose, up to 5 mg twice daily for at least 6 months
versus
placebo
patient within 3–10 days of a MI,with clinical evidence of heart failureDouble blind
Follow-up duration: 1.25 y
14 countries
Gordon, 1991
ramipril 10mg/d
versus
placebo
patients with herat failure and LVFE<=35%double blind
Follow-up duration: 12 weeks
USA
Gundersen, 1994
ramipril titrated from 1.25 mg to a maximum of 10 mg once daily
versus
placebo
patients with NYHA II-III CHF, LVFE<=40% and size of the heart >600ml/m2 for mean or >550ml/m2 for womendouble blind
Follow-up duration: 12 weeks
four Nordic countries
Lemarie, 1992
ramipril 2.5mg twice daily
versus
placebo
patient with NYHA II-III heart failuredouble blind
Follow-up duration: 24 weeks
France
Maass-a, 1991
ramipril
versus
placebo
patients with heart failure
Maass-b, 1991
ramirpil 5 or 10 mg once daily
versus
placebo
patient with NYHA II-III heart failure and LVFE<=40%double blind
Follow-up duration: 12 weeks
Europe
Maass-c, 1991
ramipril 10mg once daily
versus
placebo
patient with heart failure with LVFE<=35%double blind
Follow-up duration: 12 weeks
rolofylline versus placebo
PROTECT-1,
NCT00328692

versus
rosuvastatin versus placebo
CORONA, 2007
NCT00206310
rosuvastatin 10mg/d
versus
placebo
patients at least 60 years of age with NYHA class II, III, or IV ischemic, systolic heart failuredouble blind
Follow-up duration: 32.9 months median
Krum, 2007
rosuvastatine 40mg/d
versus
placebo
patients with systolic (LVEF<40%) CHF of ischemic or nonischemic etiologydouble blind
Follow-up duration: 6 months
Australia
GISSI-HF rosuvastatine, 2008
NCT00336336
low-dose rosuvastatin 10 mg daily
versus
placebo
Patients with NYHA classes II to IV heart failure, whatever the cause and the LVEF and already receiving optimized recommended therapy with no clear indication or contraindication to cholesterollowering therapydouble blind
Follow-up duration: 3.9y median (IQR 3-4.4)
Italy
sacubitril/valsartan versus enalapril
PARADIGM-HF, 2014
NCT01035255

versus
serelaxin versus placebo
Pre-RELAX-AHF, 2009
NCT00520806
intravenous relaxin for 48 hours: 10µg/kg daily, 30µg/kg daily, 100µg/kg daily, 250µg/kg daily
versus
placebo
Patients hospitalized with acute heart failure double blind
simvastatin versus control
Hong, 2005
simvastatin
versus
no treatment
patients with ischemic heart failure who underwent percutaneous coronary intervention (PCI) for acute myocardial infarction (left ventricular [LV] ejection fraction <40%)open
Follow-up duration: 1 year
simvastatin versus ezetimibe
Landmesser, 2005
simvastatin 10mg/d
versus
ezetimibe 10mg/d
patients with chronic heart failure
simvastatin versus placebo
Node, 2003
simvastatin 10mg/d
versus
placebo
patients with symptomatic, nonischemic, dilated cardiomyopathy
spirapril versus placebo
CASSIS (spirapril), 1995
spirapril 1.5 mg, 3 mg, 6 mg daily
versus
placebo
patients with chronic congestive heart failure of NYHA classes II-IVdouble blind
Follow-up duration: 12 weeks
spironolactone versus control
Cicoira, 2002
spironolactone 12.5 to 50 mg/day
versus
control
patients with chronic heart failure open
Follow-up duration: 12 months
Cicoira, 2004
spironolactone
versus
control
chronic heart failure patients open
Follow-up duration: 12 months
Ramires, 2000
spironolactone
versus
standard medical treatment
patients with systolic dysfunction and NYHA class III CHF secondary to dilated or ischemic cardiomyopathyopen
Follow-up duration: 20 weeks
spironolactone versus placebo
Agostoni, 2005
spironolactone 25mg/d
versus
placebo
stable chronic heart failure patients with reduced influences lung diffusion (DLCO) open
Follow-up duration: 6 months
Italy
Barr, 1995
spironolactone 50 to 100 mg/day, titrated to blood pressure and plasma potassium (added to an angiotensin-converting enzyme inhibitor)
versus
placebo
patients with New York Heart Association II to III congestive heart failure double blind
Follow-up duration: 8 weeks
Farquharson, 2000
spironolactone 50 mg/d
versus
placebo
patients with NYHA class II to III chronic heart failure on standard diuretic/ACE inhibitor therapydouble blind
Follow-up duration: 4 weeks
Macdonald, 2004
spironolactone 12.5-50 mg/d
versus
placebo
patients with New York Heart Association class I-II congestive heart failure taking optimal treatment (including beta blockers)double blind
Follow-up duration: 3 months
MacFadyen, 1997
spironolactone (50-100 mg/day)
versus
placebo
patients with stable chronic heart failuredouble blind
Follow-up duration: 8 weeks
Mottram, 2004
spironolactone 25 mg/d
versus
placebo
hypertensive patients with diastolic heart failuredouble blind
Follow-up duration: 6 months
RALES, 1998
spironolactone (25 to 50 mg daily)
versus
placebo
patients with severeheart failureOpen
Follow-up duration: 24 mo
World
Tsutamoto, 2001
spironolactone 25 mg daily
versus
placebo
patients with mild-to-moderate nonischemic congestive heart failuredouble blind
Follow-up duration: 12 weeks
Japan
Yee, 2001
spironolactone 50mg/d
versus
placebo
patients with New York Heart Association class II to IV congestive heart failuredouble blind
Follow-up duration: 4 weeks
TOPCAT, 2014
NCT00094302
spironolactone (15 to 45 mg daily)
versus
placebo
patients with heart failure and a preserved left ventricular ejection fraction of 45% or more double-blind
Follow-up duration: 3.3 years
spironolactone+captopril versus captopril
Han, 1994
captopril plus spironolactone
versus
captopril alone
patients with refractory CHF and New York Heart Association functional class IV without renal dysfunction, hypotension and hyperkalemiaopen
Follow-up duration: 4 weeks
China
spironolactone+furosemide versus spironolactone+butizide
Mauersberger, 1985
spironolactone 50mg + furosemide 20 mg
versus
spironolactone 50mg + butizide 5mg
patients with congestive heart failureopen
Stem cells versus control
TAC-HFT, 2014
NCT00768066
transendocardial injection of bone marrow-derived progenitor cells
versus
placebo
Patients With Chronic Ischemic Left Ventricular Dysfunction and Heart Failure Secondary to Myocardial Infarction
structured exercise training versus control
Patwala, 2009
program of physician-supervised exercise training
versus
control
patients with chronic systolic heart failure receiving a Cardiac Resynchronization Therapy deviceopen
Follow-up duration: 6 months
HF-ACTION, 2008
NCT00047437
highly structured exercise program focused on increasing workout intensity and duration
versus
usual care,including recommendations for daily exercise
heart-failure patients (NYHA class 2-4, ejection fraction <35%) open
Follow-up duration: mean 2.5 y
USA, Canada, France
telemonitoring versus control
TELE-HF, 2010
telemonitoring-guided management
versus
usual care
patients with an HF hospitalization within the previous month open
Follow-up duration: 180 days
US
telmisartan versus enalapril
REPLACE, 2001
Telmisartan, 10 mg, 20mg, 40mg, 80mg daily
versus
Enalapril, 10 mg twice daily
ambulatory patients at least 21 years of age, in sinus rhythm, with chronic moderatesymptomatic heart failure (New York Heart Associatality.tion class II–III) and a left ventricular ejection fraction of 40% or lowerDouble blind
Follow-up duration: 12 wk
tolvaptan versus placebo
EVEREST Clinical Status , 2007
NCT00071331

versus
patients hospitalized with heart failure
EVEREST Outcome, 2007

versus
patients hospitalized with heart failure
tovalpan versus placebo
Udelson, 2007
NCT00043758
tolvaptan 30 mg/day
versus
placebo
patients with HF and reduced systolic functiondouble blind
Follow-up duration: 1 year
trandolapril versus placebo
TRACE, 1995
Trandolapril 1 mg daily initial dose, up to 4 mg daily
versus
placebo
patient within 3–7 days of a MI,Wall motion index <1·2 (LVEF <35%)Double blind
Follow-up duration: 3 y
Denmark
Hampton, 1998
trandolapril titrated up to 4mg/d
versus
placebo
patients with moderate (New York Heart Association Grades II and III) heart failuredouble blind
Follow-up duration: 16 weeks
Ultrafiltration versus Diuretics
UNLOAD,
NCT00124137
Ultrafiltration (Aquadex system)
versus
IV Diuretics
Patients Hospitalized for Acute Decompensated Heart Failureopen
valsartan versus enalapril
HEAVEN, 2002
Valsartan, 160 mg daily
versus
Enalapril, 10 mg twice daily
Men and women with mild/moderate heart failure stabilised on an angiotensin-converting enzyme inhibitor and left ventricular ejection fraction 0.45 or lessDouble blind
Follow-up duration: 12 wk
NA
valsartan versus Lisinopril
Mazayev et al. (vs lisinopril, 1998
Valsartan, 40 mg, 80mg, 160mg twice daily
versus
lisinopril 10mg once daily
patients with chronic heart failureNA
Follow-up duration: 4 wk
Russia
valsartan versus no valsartan
VALIDD, 2007
NCT00170924
valsartan titrated up to 320 mg once daily
versus
placebo
Patients with hypertension and evidence of diastolic dysfunctiondouble blind
Follow-up duration: 38 weeks
USA, canada
valsartan versus placebo
Mazayev et al. (vs placebo), 1998
valsartan 40, 80 or 160 mg twice daily
versus
Placebo
patients with chronic heart failure previously untreated with ACE inhibitorsDouble blind
Follow-up duration: 4 wk
Russia
valsartan+ACE inhibitor versus ACE inhibitor only
V-HeFT, 1999
Valsartan 80 mg and 160mg twice daily (plus ACE inhibitor)
versus
Placebo (plus usual ACE inhibitor)
Patients with stable symptomatic congestive heart failure (CHF) receiving long-term ACE inhibitor therapy (NYHA functional class II,III, or IV) and PCWP >or=to 15 mm HgDouble blind
Follow-up duration: 4 wk
US
Val-HeFT, 2001
Valsartan, 160 mg twice daily (plus ACE inhibitor)
versus
Placebo (plus ACE inhibitor)
patients with heart failure of New York Heart Association (NYHA) class II, III, or IVDouble blind
Follow-up duration: 23 mo
16 countries
various diuretics versus placebo
De jong, 1994
diuretics
versus
placebo (diuretics withdrawal)
patients aged 65 years or older and taking diuretic drugsdouble blind
Follow-up duration: 8 weeks
the Netherlands
Myers, 1982
various diuretics
versus
placebo (withdrawals)
elderly not receiving concurrent digoxin therapydouble blind
Follow-up duration: 52 weeks
Walma, 1997
various diuretics
versus
placebo (withdrawals)
elderly patients taking long-term diuretics without manifest heart failure or hypertensiondouble blind
Follow-up duration: 14 weeks
Vesnarinone versus placebo
OPC-8212 MRG, 1990
Vesnarinone 60mg/d
versus
placebo
NYHA II-IVdouble blind
Follow-up duration: 3 months
VEST, 1998
Vesnarinone 30, 60mg/d
versus
placebo
NYHA III,IVdouble blind
Follow-up duration: 9 months
VSG, 1993
Vesnarinone 60mg/d
versus
placebo
NYHA II-IVdouble blind
Follow-up duration: 6 months
warfarin versus aspirin
HELAS (warfarin vs aspirin), 2006
warfarin
versus
aspirin 325mg/d
HF related to ischemic heart disease with LVFE<35%Double blind
Follow-up duration: 21.9 months
Europe
WATCH (warfarin vs aspirin), 2009
NCT00007683
warfarin (target INR 2.5-3.0)
versus
aspirin 162 mg daily
symptomatic heart failure patients in sinus rhythm with ejection fractions 35% taking angiotensin-converting enzyme inhibitors (unless not tolerated) and diureticsopen
warfarin versus no treatment
WASH (warfarin), 2004
warfarin (target INR 2.5)
versus
no treatment
patients with heart failure and left ventricular systolic dysfunction requiring diuretic therapy with LVEF<=35%open
Follow-up duration: 27 months
UK, US
warfarin versus placebo
HELAS (warfarin vs placebo), 2006
warfarin (target INR of 2–3)
versus
placebo
HF due to dilated cardiomyopathy double blind
Follow-up duration: 21.9 months
Europe
Barzizza (warfarin), 1993
warfarin to maintain INR between 2 and 3
versus
placebo
patients with dilated cardiomyopathy and evidence of intraventricular thrombi NA
Follow-up duration: 6 months