heart failure

systematic review meta-analysis network meta-analysis

Select surgerycell-based therapies regenerative therapyBNP guided management telemonitoringaldosterone blockade diureticsmineralocorticoid receptor antagonists percutaneous left ventricular assist devicesresynchronization (CRT) - defibrillators (ICD)cholesterol lowering interventionstatinsanticoagulantantithromboticsdirect oral anticoagulant (DAO)angiotensin-Converting Enzyme Inhibitorsangiotensin-receptor blockerscombined inhibition of ACE and neprilysininhibition of the renin-angiotensin system (ACEI or ARB)renin inhibitor anti inflammatory drugsantiarrythmic drugsbeta-blockerscalcium channel blockersdigitalis glycosidesExercise TherapyHR-slowing agentsincreasing hemoglobin concentration Miscellaneousnew drug under developmentphosphodiesterase III inhibitors relaxinevasodilators therapyvasopeptidase inhibitorvasopressin antagonist acute decompensated heart failureuncoded clinical condition ***all type of heart failureAll type of patientelderly patientsLeft Ventricular Dysfunction after Myocardial InfarctionMI patients with LV dysfunction without clinical evidence of HFpatients already receiving ACE inhibitorpatients already taking diureticspatients hospitalized for heart failurepatients intolerant to ACE inhibitorspatients previously untreated with ACE inhibitorspatients undergoing CABGpatients with non ichaemic cardiomyopathypatients with preserved-LVEF heart failurepost myocardial infarctionsurvivors of cardiac arrest       adenosine A1 receptor antagonistaldosterone-receptor blockersamiodaroneangiotensin receptor blockerAngiotensin-Converting Enzyme Inhibitorsanti-inflammatoryanticoagulantARBs added to ACEIbeta-blockersBNP-guided managementbone marrow derived stem cellcalcium-channel blockerscardiac resynchronization therapyCardiac stem cellsCombined CRT + ICDdevicedigoxindirect oral anticoagulantDiureticsdronedaroneepoprostenolerythropoeitinexercise traininggene therapyhuman B-type natriuretic peptidehydralazinehydralazine-ISDNImplantable cardioverter defibrillator therapyintravenous ironisosorbide dinitrateivabradineixmyelocel-TLow Molecular Weight Heparinmineralocorticoid receptor antagonistsmyoblastsoral vasopressin antagonistPhosphodiesterase III inhibitorsplatelet aggregation inhibitorsprazosinrelaxinestatinstelemonitoringvasopeptidase inhibitorventricular assist device atorvastatincerivastatinrosuvastatinsimvastatinamlodipinediltiazemfelodipinenicardipinenisoldipinecaptoprilenalaprilfosinoprillisinoprilperindoprilquinaprilramipriltrandolaprilirbesartanlosartantelmisartanvalsartancandesartanaliskiren amilorideamiodaroneamrinoneaspirinbenazeprilbisoprololbucindololcarvedilolcilazaprilclopidogreldigoxindronedaroneenoxaparinEnoximoneeplerenoneepoprostenolExercise TherapyFlosequinanfurosemidehydralazinehydralazine-ISDNhydrochlorothiazide ibopamineisosorbide dinitrateisradipineivabradinemetoprololmibefradilMilrinonenebivololnesiritideomapatrilatrivaroxabanrolofylline serelaxinspironolactonetaspoglutidetolvaptanvesnarinonewarfarin vs angiotensin receptor blockervs controlvs placebovs placebo or controlvs placebo or no treatmentvs usual carevs active treatmentvs angiotensin-converting enzyme inhibitorsvs antiplatelet drugsvs beta-blockersvs ezetimibevs ICDvs medical treatmentvs UFHvs vasodilatorsvs ventricular assist device      

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Group by Group by... nothing pathology treatment patient comparator classe classe comparator mechanism clinical condition MA  in first nothing pathology treatment patient comparator classe classe comparator mechanism clinical condition  in second nothing pathology treatment patient comparator classe classe comparator mechanism clinical condition  in third	Description Synopsis Comparison Treatments Patients Characteristics Method Risk of bias References None Tools Indexation					Results Global trial result Main results All results All result tag NCT results	All cause death (274)hospitalisation for heart failure (68)Death from any cause or hospitalization for any reason (67)Cardiovascular death (46)Sudden death (38)NYHA class improvement (35)Adverse events (34)exacerbation of heart failure (26)Hospitalization for any reason (19)Hypotension (14) (12)myocardial infarction (fatal and non fatal) (12)Worsening heart failure (11)cardiac death (10)Arrhythmia (10)Hyperkalaemia (9)Cough (9)angiodema (8)stroke (fatal and non fatal) (8)Vertigo (7)Cardiovascular death or hospital admission for CHF (7)acute heart failure (6)cardiovascular events (6)Major bleeding (6)hospitalisation for cardiovascular causes (6)serious hyperkalemia (6)heart failure death (6)Non fatal MI (5)Coronary event (5)Fatal stroke (5)Fatal MI (5)Non vascular death (5)new-onset diabetes (5)Long term death (5)death or hospitalization (5)Death from any cause or hospitalization for heart failure (5)Transplantation (4)NYHA deterioration (4)death from cardiovascular causes or hospitalization for cardiovascular causes (3)Non fatal stroke (3)death or cardiovascular hospitalization (3)All-cause hospitalisation (2)Adverse events leading to treatment discontinuation (2)Coronary death (2)death or nonfatal CHF events (2)death or severe congestive heart failure (1)CV death, MI hospitalization for HF (1)amelioration of Dyspnea at 24 h (1)30-day death (1) Options Numeric bar chart forest plot medians
Trial	Studied trt	Control trt	patients	tags	ROB	Trial result	All cause death	hospitalisation for heart failure
aldosterone blockade
eplerenone
EPHESUS, 2003	eplerenone	placebo			Low risk of bias	suggesting
EMPHASIS-HF, 2010        NCT	eplerenone	placebo			Low risk of bias	suggesting
spironolactone
Cicoira, 2004	spironolactone	control				-
Cicoira, 2002	spironolactone	control			Exploratory	-
Ramires, 2000	spironolactone	control			Exploratory	-
RALES, 1998	spironolactone	placebo			Risk of bias	suggesting
Agostoni, 2005	spironolactone	placebo			Exploratory	-
Mottram, 2004	spironolactone	placebo			Low risk of bias	-
Macdonald, 2004	spironolactone	placebo			Low risk of bias	-
Yee, 2001	spironolactone	placebo			Low risk of bias	-
Tsutamoto, 2001	spironolactone	placebo			Low risk of bias	-
Farquharson, 2000	spironolactone	placebo			Low risk of bias	-
MacFadyen, 1997	spironolactone	placebo			Low risk of bias	-
Han, 1994	spironolactone+captopril	captopril			Exploratory	-
Bednarz, 2000	aldactone	furosemide			Exploratory	-
Mauersberger, 1985	spironolactone+furosemide	spironolactone+butizide			Exploratory	-
angiotensin-Converting Enzyme Inhibitors
not classified
CASSIS (spirapril), 1995	spirapril	placebo			Low risk of bias	-
benazepril
McGany, 1991	benazepril	control				negative
Colfer, 1992	benazepril	placebo			Low risk of bias	negative
captopril
Magnani, 1986	captopril	placebo			Low risk of bias	-
Bussmann, 1987	captopril	placebo			Low risk of bias	negative
Captopril Digoxin Multicenter Research Group, 1988	captopril	placebo			Low risk of bias	negative
Barabino, 1991	captopril	placebo			Low risk of bias	suggesting
Munich MHFT (Kleber), 1992	captopril	placebo			Low risk of bias	negative
Magnani, 1990	captopril	placebo			Low risk of bias	-
CMRG, 1983	captopril	placebo			Low risk of bias	-
Cilazapril-Captopril Multi-centre Group (capt vs pbo), 1995	captopril	placebo			Low risk of bias	-
SAVE, 1992	captopril	placebo			Low risk of bias	-
Pfeffer, 1988	captopril	placebo			Low risk of bias	-
Sogaard, 1994	captopril	placebo			Low risk of bias	-
Sharpe, 1988	captopril	placebo			Low risk of bias	-
Mortarino, 1990	captopril	placebo			Low risk of bias	-
packer, 1986	captopril	enalapril			Exploratory	-
cilazapril
Drexler, 1989	cilazapril	placebo			Low risk of bias	negative
Dosseger, 1993	cilazapril	placebo			Low risk of bias	-
Cilazapril-Captopril Multi-centre Group, 1995	cilazapril	placebo			Low risk of bias	-
Cilazapril-Captopril Multi-centre Group (cila vs capt), 1995	cilazapril	captopril			Low risk of bias	-
enalapril
Rucinska-b (enalapril), 1991	enalapril	control				negative
Enalapril CHF investigators, 1987	enalapril	control				negative
Rucinska-a (enalapril), 1991	enalapril	control				negative
SOLVD treatment, 1991    NCT	enalapril	placebo			Low risk of bias	suggesting
SOLVD prevention, 1992    NCT	enalapril	placebo			Low risk of bias	-
Cleland, 1985	enalapril	placebo			Low risk of bias	negative
CONSENSUS, 1987	enalapril	placebo			Low risk of bias	negative
Dickstein, 1991	enalapril	placebo			Low risk of bias	negative
Sharpe, 1984	enalapril	placebo			Low risk of bias	-
McGrath, 1985	enalapril	placebo			Low risk of bias	-
Chrysant, 1985	enalapril	placebo			Low risk of bias	-
CASSIS (enalapril), 1995	enalapril	placebo			Low risk of bias	-
NETWORK (2.5 bid vs 10 bid), 1998	enalapril	enalapril			Low risk of bias	-
NETWORK (5 bid vs 10 bid), 1998	enalapril	enalapril			Low risk of bias	-
V-HeFT II, 1991	enalapril	hydralazine+ISDN			Low risk of bias	-
fosinopril
Brown, 1995	fosinopril	placebo			Low risk of bias	-
FEST (Erhardt), 1996	fosinopril	placebo			Low risk of bias	-
lisinopril
Zwehl, 1990	lisinopril	control				negative
Giles, 1990	lisinopril	control				negative
Rucinska-c (lisinopril), 1000	lisinopril	control				negative
Gilbert, 1993	lisinopril	placebo			Low risk of bias	negative
International Study Group (Lewis), 1989	lisinopril	placebo			Low risk of bias	-
ATLAS, 1999	lisinopril	lisinopril			Low risk of bias	-
perindopril
Lechat, 1993	perindopril	placebo			Low risk of bias	negative
PEP CHF, 2006	perindopril	placebo			Low risk of bias	negative
quinapril
Uprichard-a, 1994		control				negative
Uprichard-b, 1994		control				negative
Uprichard-c, 1994		control				negative
Riegger, 1990		placebo			Low risk of bias	negative
Northridge, 1991		placebo			Low risk of bias	negative
Rieger, 1991		placebo			Low risk of bias	negative
Nussberger, 1994		placebo			Low risk of bias	-
Quinapril Heart Failure Trial Investigators, 1993		placebo			Low risk of bias	-
ramipril
Swedberg, 1991	ramipril	control				negative
Maass-a, 1991	ramipril	placebo				negative
Gordon, 1991	ramipril	placebo			Low risk of bias	suggesting
Maass-b, 1991	ramipril	placebo			Low risk of bias	negative
Maass-c, 1991	ramipril	placebo			Low risk of bias	negative
Lemarie, 1992	ramipril	placebo			Low risk of bias	negative
Gundersen, 1994	ramipril	placebo			Low risk of bias	-
AIRE, 1993	ramipril	placebo			Low risk of bias	-
trandolapril
Hampton, 1998	trandolapril	placebo			Low risk of bias	-
TRACE, 1995	trandolapril	placebo			Low risk of bias	-
angiotensin-receptor blockers
not classified
ADEPT, 2001	eprosartan+ACE inhibitor	ACE inhibitor only			Low risk of bias	-
candesartan
ARCH-J, 2003	candesartan	placebo			Low risk of bias	-
CHARM-Alternative, 2003	candesartan	placebo			Low risk of bias	suggesting
Mitrovic et al., 2003	candesartan	placebo			Low risk of bias	suggesting
SPICE, 2000	candesartan	placebo			Low risk of bias	negative
STRETCH, 1999	candesartan	placebo			Low risk of bias	-
CHARM preserved, 2003	candesartan	placebo			Low risk of bias	-
CHARM-Added, 2003	candesartan+ACE inhibitor	ACE inhibitor only			Low risk of bias	negative
RESOLVD association, 1999	candesartan+ACE inhibitor	ACE inhibitor only			Exploratory	negative
RESOLVD (candesartan alone), 1999	candesartan	enalapril			Low risk of bias	negative
irbesartan
I-PRESERVE (McMurray), 2008      NCT	ibesartan	placebo			Low risk of bias	negative
Tonkon et al., 2000	irbesartan+ACE inhibitor	ACE inhibitor only			Low risk of bias	-
losartan
HEAAL, 2009        NCT	losartan 150mg	losartan 50mg			Low risk of bias	suggesting
Losartan Phase III International, 1996	losartan	placebo			Low risk of bias	suggesting
Losartan Phase III U.S., 1995	losartan	placebo			Low risk of bias	negative
Hamroff et al., 1999	losartan+ACE inhibitor	ACE inhibitor only			Low risk of bias	-
ELITE, 1997	losartan	captopril			Low risk of bias	negative
ELITE II, 2000	losartan	captopril			Low risk of bias	-
Dickstein et al., 1995	losartan	enalapril			Low risk of bias	-
Lang et al., 1997	losartan	enalapril			Low risk of bias	-
Losartan phase II S, 1996	losartan	enalapril			Low risk of bias	-
losartan phase II US, 1996	losartan	enalapril			Low risk of bias	-
telmisartan
REPLACE, 2001	telmisartan	enalapril			Low risk of bias	-
valsartan
VALIDD, 2007    NCT	valsartan	no valsartan			Low risk of bias	negative
Mazayev et al. (vs placebo), 1998	valsartan	placebo			Low risk of bias	-
V-HeFT, 1999	valsartan+ACE inhibitor	ACE inhibitor only			Low risk of bias	negative
Val-HeFT, 2001	valsartan+ACE inhibitor	ACE inhibitor only			Low risk of bias	suggesting
HEAVEN, 2002	valsartan	enalapril			Low risk of bias	-
Mazayev et al. (vs lisinopril, 1998	valsartan	Lisinopril			Exploratory	-
anti inflammatory drugs
not classified
ACCLAIM, 2008      NCT	Celacade™ system	placebo			Low risk of bias	negative
antiarrythmic drugs
amiodarone
EPAMSA, 1985	amiodarone	no treatment				suggesting
GESICA, 1994	amiodarone	no treatment				suggesting
Hamer, 1989	amiodarone	placebo			Low risk of bias	suggesting
Nicklas, 1991	amiodarone	placebo			Low risk of bias	negative
STATCHF, 1995	amiodarone	placebo			Low risk of bias	negative
AMIOVIRT, 2003	amiodarone	ICD				negative
dronedarone
ANDROMEDA, 2008      NCT	dronedarone	placebo			Low risk of bias	negative
anticoagulant
rivaroxaban
COMMANDER HF, 2018      NCT	rivaroxaban	placebo				negative
warfarin
HELAS (warfarin vs placebo), 2006	warfarin	placebo			Low risk of bias	-
HELAS (warfarin vs aspirin), 2006	warfarin	aspirin			Low risk of bias	-
WATCH (warfarin vs aspirin), 2009      NCT	warfarin	aspirin				suggesting
antithrombotics
not classified
Barzizza (A+D), 1993		placebo				-
aspirin
WASH (aspirin), 2004	aspirin	no treatment				negative
Barzizza (ASA), 1993	aspirin	placebo			Exploratory	-
enoxaparin
THE-PRINCE (Kleber), 2003	enoxaparin	UFH				-
rivaroxaban
COMMANDER HF, 2018      NCT	rivaroxaban	placebo				negative
warfarin
WASH (warfarin), 2004	warfarin	no treatment				negative
HELAS (warfarin vs placebo), 2006	warfarin	placebo			Low risk of bias	-
Barzizza (warfarin), 1993	warfarin	placebo				-
HELAS (warfarin vs aspirin), 2006	warfarin	aspirin			Low risk of bias	-
WATCH (warfarin vs aspirin), 2009      NCT	warfarin	aspirin				suggesting
beta-blockers
bisoprolol
CIBIS, 1994	bisoprolol	placebo			Low risk of bias	suggesting
CIBIS II, 1999	bisoprolol	placebo			Low risk of bias	suggesting
CIBIS II (elderly subgroup), 1999	Bisoprolol	placebo				suggesting
bucindolol
BEST, 2001    NCT	bucindolol	placebo			Low risk of bias	suggesting
Pollock, 1990	Bucindolol	placebo			Low risk of bias	-
Woodley, 1991	Bucindolol	placebo				-
Bristow, 1994	Bucindolol	placebo				-
MERIT-HF (elderly subgroup), 1999	Bucindolol	placebo				suggesting
carvedilol
ANZ-HeFT, 1997	carvedilol	placebo			Low risk of bias	negative
COPERNICUS, 2002	carvedilol	placebo			Low risk of bias	suggesting
CAPRICORN, 2001	carvedilol	placebo			Low risk of bias	suggesting
Metra, 1994	carvedilol	placebo				-
Olsen, 1995	carvedilol	placebo				-
Krum, 1995	carvedilol	placebo				-
Bristow (MOCHA), 1996	carvedilol	placebo			Low risk of bias	-
Parker, 1996	carvedilol	placebo			Low risk of bias	negative
Colucci, 1996	carvedilol	placebo			Low risk of bias	-
Cohn, 1997	carvedilol	placebo				-
Carvedilol U.S. Trials (elderly subgroup), 1996	Carvedilol	placebo				suggesting
COPERNICUS (elderly subgroup), 2001	Carvedilol	placebo				suggesting
CARMEN (carvedilol alone), 2004	carvedilol	enalapril				negative
COMET, 2003	carvedilol	metoprolol			Low risk of bias	suggesting
metoprolol
MDC (Waagstein), 1993	metoprolol	placebo			Low risk of bias	negative
MERIT-HF, 1999	metoprolol	placebo			Low risk of bias	suggesting
Engelmeier, 1985	metoprolol	placebo				-
Fisher, 1994	metoprolol	placebo				-
Eichhorn, 1994	metoprolol	placebo				-
RESOLVD, 2000	metoprolol	placebo				-
BEST (elderly subgroup), 2001	Metoprolol	placebo				negative
nebivolol
Lechat, 1991	Nebivolol	placebo				-
Wisenbaugh, 1993	Nebivolol	placebo			Low risk of bias	negative
SENIORS, 2005	nebivolol	placebo			Low risk of bias	-
BNP guided management
not classified
TIME CHF, 2009	BNP-guided management	control			Risk of bias	negative
PRIMA	BNP-guided management	control			Risk of bias	negative
PROTECT, 2009    NCT	BNP-guided management	control				-
STARS-BNP, 2007	BNP-guided management	control			Risk of bias	suggesting
BATTLESCARRED, 2009	BNP-guided management	control			Risk of bias	negative
STARBRITE, 2007    NCT	BNP-guided management	control				-
Troughton, 2000	BNP-guided management	control			Risk of bias	suggesting
calcium channel blockers
not classified
De Vries, 1996		placebo			Low risk of bias	-
amlodipine
Packer, 1991	amlodipine	control			Low risk of bias	-
Smith, 1994	amlodipine	control			Low risk of bias	-
Udelson, 1996	amlodipine	control			Low risk of bias	-
Binkley, 1996	amlodipine	control			Low risk of bias	-
Ghali, 1997	amlodipine	control			Low risk of bias	-
PRAISE, 1996	amlodipine	placebo			Low risk of bias	negative
PRAISE II , 2000	Amlodipine	placebo			Low risk of bias	negative
diltiazem
Liao , 1998	Diltiazem	placebo			Exploratory	suggesting
DiDi, 1996	diltiazem	placebo			Low risk of bias	negative
felodipine
VHeFT III, 1997	felodipine	placebo			Low risk of bias	negative
Kassis, 1987	felodipine	placebo			Low risk of bias	-
Littler, 1995	Felodipine	placebo			Low risk of bias	negative
Kassis, 1990	felodipine	placebo			Low risk of bias	-
Dunselman, 1990	felodipine	enalapril			Low risk of bias	-
De Vries, 1995	felodipine	enalapril			Low risk of bias	-
isradipine
Van den Toren, 1996	isradipine	placebo			Low risk of bias	-
mibefradil
MACH 1, 2000	mibefradil	placebo			Low risk of bias	suggesting
nicardipine
Gheorghiade, 1991	nicardipine	control			Low risk of bias	-
Abrams, 1993	nicardipine	control			Low risk of bias	-
nisoldipine
Gaudron, 1996	Nisoldipine	placebo			Exploratory	-
Rousseau, 1994	nisoldipine	placebo			Low risk of bias	-
Schofer, 1990	nisoldipine	captopril			Low risk of bias	-
cell-based therapies
not classified
Revive						-
POSEIDON, 2012      NCT	Mesenchymal stem cells	allogeneic mesenchymal stem cells				-
Pokushalov (DOUBLON DIB), 2010	Bone marrow derived stem cell	control				-
FOCUS-CCTRN, 2012      NCT	Bone marrow derived stem cell	control				-
CUPID 2b, 2016      NCT	Bone marrow derived stem cell	control				-
TOPCARE-CHD, 2006	Bone marrow mononuclear cells	control				-
Hendrikx, 2006	Bone marrow mononuclear cells	control				-
Yao, 2008	Bone marrow mononuclear cells	control				-
Ang, 2008	Bone marrow mononuclear cells	control				-
Patel, 2005	Bone marrow progenitor cells	control				-
Manginas, 2007	Bone marrow progenitor cells	control				-
Vrtovec, 2011      NCT	Bone marrow progenitor cells	control				-
Vrtovec, 2013      NCT	Bone marrow progenitor cells	control				-
Perin, 2012	Bone marrow progenitor cells	control				-
SCIPIO, 2011        NCT	Cardiac stem cells	control				-
C CURE, 2013        NCT	Cardiopoietic stem cell	control				-
CADUCEUS, 2012      NCT	Cardiopoietic stem cell	control				-
IMPACT-DCM, 2014    NCT	ixmyelocel-T	control				-
Catheter-DCM, 2014      NCT	ixmyelocel-T	control				-
CAuSMIC, 2005	myoblasts	control				negative
SEISMIC, 2011	myoblasts	control				negative
TAC-HFT, 2014      NCT	Stem cells	control				-
INCL, 2015      NCT	Bone marrow derived stem cell	placebo			Low risk of bias	-
ABCD, 2010	Bone marrow derived stem cell	placebo				-
FOCUS-HF, 2011      NCT	Bone marrow mononuclear cells	placebo				negative
CUPID, 2011	gene therapy	placebo			Exploratory	-
ixCELL-DCM, 2016      NCT	ixmyelocel-T	placebo				-
MAGIC, 2001	myoblasts	placebo				negative
MARVEL, 2011      NCT	myoblasts	placebo				negative
cholesterol lowering intervention
atorvastatin
Wojnicz, 2006	atorvastatin	control	heart failure			negative
Yamada, 2007	atorvastatin	control	heart failure			negative
Strey, 2005	atorvastatin	placebo	heart failure			-
Sola, 2006	atorvastatin	placebo	heart failure		Low risk of bias	negative
cerivastatin
Laufs, 2004	cerivastatin	placebo	heart failure		Low risk of bias	-
rosuvastatin
CORONA, 2007      NCT	rosuvastatin	placebo	heart failure		Low risk of bias	negative
Krum, 2007	rosuvastatin	placebo	heart failure		Low risk of bias	negative
GISSI-HF rosuvastatine, 2008      NCT	rosuvastatin	placebo	heart failure		Low risk of bias	negative
simvastatin
Hong, 2005	simvastatin	control	heart failure		Risk of bias	negative
Node, 2003	simvastatin	placebo	heart failure			negative
Landmesser, 2005	simvastatin	ezetimibe	heart failure			-
combined inhibition of ACE and neprilysin
not classified
PARADIGM-HF, 2014      NCT	sacubitril/valsartan	enalapril				-
digitalis glycosides
digoxin
Fleg, 1982	digoxin	placebo				negative
Lee, 1982	digoxin	placebo			Low risk of bias	negative
Taggart, 1983	digoxin	placebo			Low risk of bias	negative
Captopril-Digoxin Multicenter Research Group (CDMRG), 1988	digoxin	placebo			Low risk of bias	suggesting
German and Austrian Xamoterol Study, 1988	digoxin	placebo			Low risk of bias	negative
Guyatt, 1988	digoxin	placebo			Low risk of bias	negative
DiBianco, 1989	digoxin	placebo			Low risk of bias	suggesting
Pugh, 1989	digoxin	placebo			Low risk of bias	negative
Blackwood, 1990	digoxin	placebo			Low risk of bias	negative
Radiance, 1993	digoxin	placebo			Low risk of bias	suggesting
Proved, 1993	digoxin	placebo			Low risk of bias	negative
DIMT, 1993	digoxin	placebo			Low risk of bias	negative
Digitalis Investigation Group (DIG), 1997      NCT	digoxin	placebo			Low risk of bias	suggesting
direct oral anticoagulant (DAO)
rivaroxaban
COMMANDER HF, 2018      NCT	rivaroxaban	placebo				negative
diuretics
not classified
Burr, 1977	diuretic agents	placebo			Low risk of bias	negative
Mathur, 1984	furosemide	placebo			Low risk of bias	-
Sherman, 1986	piretanide	placebo			Low risk of bias	negative
TOPCAT, 2014      NCT	spironolactone	placebo			Low risk of bias	-
De jong, 1994	various diuretics	placebo			Low risk of bias	negative
Myers, 1982	various diuretics	placebo			Low risk of bias	negative
Walma, 1997	various diuretics	placebo			Low risk of bias	suggesting
Richardson, 1987	frusemide plus amiloride	captopril			Low risk of bias	negative
Haerer, 1989	piretanide	digoxin			Low risk of bias	-
UNLOAD      NCT	Ultrafiltration	Diuretics			Exploratory	-
Myers (copie de 7314), 1982	placebo (diuretics withdrawal)	various diuretics			Low risk of bias	-
amiloride
Cheitlin, 1991	amiloride	placebo			Low risk of bias	-
eplerenone
EMPHASIS-HF, 2010        NCT	eplerenone	placebo			Low risk of bias	suggesting
EPHESUS, 2003	eplerenone	placebo			Low risk of bias	suggesting
furosemide
Boccanelli, 1986	furosemide	captopril			Low risk of bias	negative
Cowley, 1986	furosemide	captopril			Low risk of bias	-
hydrochlorothiazide
Nordrehaug, 1992	hydrochlorothiazide	benazepril			Low risk of bias	suggesting
Sievert, 1989	hydrochlorothiazide+triamterene	digoxin			Low risk of bias	-
rolofylline
PROTECT-1    NCT	rolofylline	placebo				-
spironolactone
Cicoira, 2004	spironolactone	control				-
Cicoira, 2002	spironolactone	control			Exploratory	-
Ramires, 2000	spironolactone	control			Exploratory	-
RALES, 1998	spironolactone	placebo			Risk of bias	suggesting
Agostoni, 2005	spironolactone	placebo			Exploratory	-
Mottram, 2004	spironolactone	placebo			Low risk of bias	-
Macdonald, 2004	spironolactone	placebo			Low risk of bias	-
Yee, 2001	spironolactone	placebo			Low risk of bias	-
Tsutamoto, 2001	spironolactone	placebo			Low risk of bias	-
Farquharson, 2000	spironolactone	placebo			Low risk of bias	-
MacFadyen, 1997	spironolactone	placebo			Low risk of bias	-
Barr, 1995	spironolactone	placebo			Low risk of bias	-
Han, 1994	spironolactone+captopril	captopril			Exploratory	-
Bednarz, 2000	aldactone	furosemide			Exploratory	-
Dalhstrom, 1986	furosemide + spironolactone	prenalterol			Low risk of bias	negative
Mauersberger, 1985	spironolactone+furosemide	spironolactone+butizide			Exploratory	-
Exercise Therapy
not classified
HF-ACTION, 2008    NCT	structured exercise training	control			Risk of bias	negative
Patwala, 2009	structured exercise training	control			Exploratory	-
Exercise Therapy
Belardinelli et al, 1999	Exercise training	control				-
Dubach et al, 1997	Exercise training	control				-
Giannuzzi et al, 1997	Exercise training	control				-
Hambrecht et al, 1995	Exercise training	control				-
Kiilavuori et al, 2000	Exercise training	control				-
McKelvie et al, 2002	Exercise training	control				-
Zanelli et al, 1997	Exercise training	control				-
Wielenga et al, 1999	Exercise training	control				-
Willenheimer et al, 1998	Exercise training	control				-
ExTraMATCH, 2004	Exercise training	control				-
HR-slowing agents
ivabradine
SHIFT, 2010	ivabradine	placebo			Low risk of bias	suggesting
BEAUTIFUL, 2008    NCT	ivabradine 15mg	placebo			Low risk of bias	negative
increasing hemoglobin concentration
not classified
Palazzuoli, 2006	beta-erythropoietin	placebo			Low risk of bias	negative
FAIR-HF (Anker), 2009	ferric carboxymaltose	placebo			Low risk of bias	-
taspoglutide
STAMINA-HeFT (Ghali), 2008      NCT	darbepoetin alfa	placebo			Low risk of bias	negative
van Veldhuisen, 2007      NCT	darbepoetin alfa	placebo			Low risk of bias	negative
Ponikowski, 2007      NCT	darbepoetin alfa	placebo			Low risk of bias	negative
Parissis, 2008	darbepoetin alfa	placebo			Exploratory	negative
Parissis, 2009	darbepoetin alfa	placebo			Exploratory	-
Kourea, 2008	darbepoetin alfa	placebo			Low risk of bias	negative
inhibition of the renin-angiotensin system (ACEI or ARB)
candesartan
CHARM preserved, 2003	candesartan	placebo			Low risk of bias	-
irbesartan
I-PRESERVE (McMurray), 2008      NCT	ibesartan	placebo			Low risk of bias	negative
perindopril
PEP CHF, 2006	perindopril	placebo			Low risk of bias	negative
mineralocorticoid receptor antagonists
not classified
TOPCAT, 2014      NCT	spironolactone	placebo			Low risk of bias	-
percutaneous left ventricular assist devices
not classified
REMATCH, 2001	pulsatile-flow	medical treatment				-
HeartMate II, 2009      NCT	continuous-flow HeartMate II	pulsatile-flow HeartMate XVE			Risk of bias	-
phosphodiesterase III inhibitors
not classified
IRG, 1991	Imazodan	placebo			Low risk of bias	negative
Dies, 1989	Indolidan	placebo			Low risk of bias	negative
Bergler-Klein, 1992	Pimobendan	placebo			Low risk of bias	negative
EPOCH, 2002	Pimobendan	placebo			Low risk of bias	negative
PICO, 1996	Pimobendan	placebo			Low risk of bias	negative
PMRG, 1992	Pimobendan	placebo			Low risk of bias	negative
amrinone
AMTG, 1985	Amrinone	placebo			Low risk of bias	negative
Enoximone
WESG, 1991	Enoximone	placebo			Low risk of bias	negative
EMTG, 1990	Enoximone	placebo			Low risk of bias	negative
ESG, 2000	Enoximone	placebo			Low risk of bias	negative
Lardoux, 1987	Enoximone	placebo			Low risk of bias	negative
ESSENTIAL (I and II), 2009    NCT	enoximone	placebo			Low risk of bias	negative
Cowley, 1994	Enoximone	placebo			Low risk of bias	negative
EMOTE, 2007	enoximone	placebo			Low risk of bias	-
Flosequinan
Cowley, 1993	Flosequinan	placebo			Low risk of bias	negative
FACET, 1993	Flosequinan	placebo			Low risk of bias	negative
REFLECT, 1993	Flosequinan	placebo			Low risk of bias	negative
REFLECT II, 1991	Flosequinan	placebo			Low risk of bias	negative
ibopamine
PRIME II, 1997	ibopamine	placebo			Low risk of bias	negative
Milrinone
PROMISE, 1991	Milrinone	placebo			Low risk of bias	negative
MMTG, 1989	Milrinone	placebo			Low risk of bias	negative
vesnarinone
OPC-8212 MRG, 1990	Vesnarinone	placebo			Low risk of bias	negative
VEST, 1998	Vesnarinone	placebo			Low risk of bias	negative
VSG, 1993	Vesnarinone	placebo			Low risk of bias	suggesting
regenerative therapy
not classified
Revive						-
POSEIDON, 2012      NCT	Mesenchymal stem cells	allogeneic mesenchymal stem cells				-
Pokushalov (DOUBLON DIB), 2010	Bone marrow derived stem cell	control				-
FOCUS-CCTRN, 2012      NCT	Bone marrow derived stem cell	control				-
CUPID 2b, 2016      NCT	Bone marrow derived stem cell	control				-
TOPCARE-CHD, 2006	Bone marrow mononuclear cells	control				-
Hendrikx, 2006	Bone marrow mononuclear cells	control				-
Yao, 2008	Bone marrow mononuclear cells	control				-
Ang, 2008	Bone marrow mononuclear cells	control				-
Patel, 2005	Bone marrow progenitor cells	control				-
Manginas, 2007	Bone marrow progenitor cells	control				-
Vrtovec, 2011      NCT	Bone marrow progenitor cells	control				-
Vrtovec, 2013      NCT	Bone marrow progenitor cells	control				-
Perin, 2012	Bone marrow progenitor cells	control				-
SCIPIO, 2011        NCT	Cardiac stem cells	control				-
C CURE, 2013        NCT	Cardiopoietic stem cell	control				-
CADUCEUS, 2012      NCT	Cardiopoietic stem cell	control				-
IMPACT-DCM, 2014    NCT	ixmyelocel-T	control				-
Catheter-DCM, 2014      NCT	ixmyelocel-T	control				-
CAuSMIC, 2005	myoblasts	control				negative
SEISMIC, 2011	myoblasts	control				negative
TAC-HFT, 2014      NCT	Stem cells	control				-
INCL, 2015      NCT	Bone marrow derived stem cell	placebo			Low risk of bias	-
ABCD, 2010	Bone marrow derived stem cell	placebo				-
FOCUS-HF, 2011      NCT	Bone marrow mononuclear cells	placebo				negative
CUPID, 2011	gene therapy	placebo			Exploratory	-
ixCELL-DCM, 2016      NCT	ixmyelocel-T	placebo				-
MAGIC, 2001	myoblasts	placebo				negative
MARVEL, 2011      NCT	myoblasts	placebo				negative
relaxine
serelaxin
Pre-RELAX-AHF, 2009      NCT	serelaxin	placebo			Low risk of bias	-
renin inhibitor
aliskiren
ASTRONAUT, 2013    NCT	Aliskiren	placebo			Low risk of bias	-
resynchronization (CRT) - defibrillators (ICD)
not classified
RethinQ, 2007      NCT	Combined CRT + ICD	no CRT			Exploratory	negative
CARE-HF, 2005	CRT	no CRT				suggesting
COMPANION (CRT vs MT), 2004	CRT	no CRT			Risk of bias	negative
MIRACLE, 2002	CRT	no CRT				suggesting
MUSTIC-SR, 2001	CRT	no CRT				negative
MUSTIC AF, 2002	CRT	no CRT				negative
Garrigue, 2002	CRT	no CRT				-
PATH-CHF, 2002	CRT	no CRT				-
RD-CHF, 2003	CRT	no CRT				negative
REVERSE, 2008      NCT	CRT	no CRT			Low risk of bias	suggesting
AMIOVIRT, 2003	Combined CRT + ICD	no CRT no ICD				-
COMPANION (CRT+ICD vs MT), 2004	Combined CRT + ICD	no CRT no ICD				suggesting
CAT, 2002	ICD	no ICD				-
DEFINITE, 2004	ICD	no ICD				-
MADIT-II, 2002	ICD	no ICD				suggesting
SCD-HeFT (ICD vs placebo), 2005      NCT	ICD	no ICD				-
MADIT, 1996	ICD	no ICD				-
CABG-patch, 1997      NCT	ICD	no ICD				-
DINAMIT, 2004	ICD	no ICD				negative
MUSIT, 1999	ICD	no ICD				-
SCD-HeFT (ICD vs amiodarone), 2005      NCT	ICD	no ICD				-
AVID, 1997      NCT	ICD	no ICD				-
CASH, 2000	ICD	no ICD				-
CIDS, 2000	ICD	no ICD				-
COMPANION (CRT+ICD vs CRT), 2004	Combined CRT + ICD	CRT				negative
CONTAK-CD , 2003	Combined CRT + ICD	ICD alone				-
MIRACLE-ICD-I, 2003	Combined CRT + ICD	ICD alone			Low risk of bias	negative
MIRACLE-ICD-II, 2004	Combined CRT + ICD	ICD alone			Low risk of bias	negative
MADIT CRT, 2009      NCT	Combined CRT + ICD	ICD alone				suggesting
RAFT, 2010    NCT	Combined CRT + ICD	ICD alone			Low risk of bias	suggesting
statins
atorvastatin
Wojnicz, 2006	atorvastatin	control	heart failure			negative
Yamada, 2007	atorvastatin	control	heart failure			negative
Strey, 2005	atorvastatin	placebo	heart failure			-
Sola, 2006	atorvastatin	placebo	heart failure		Low risk of bias	negative
cerivastatin
Laufs, 2004	cerivastatin	placebo	heart failure		Low risk of bias	-
rosuvastatin
CORONA, 2007      NCT	rosuvastatin	placebo	heart failure		Low risk of bias	negative
Krum, 2007	rosuvastatin	placebo	heart failure		Low risk of bias	negative
GISSI-HF rosuvastatine, 2008      NCT	rosuvastatin	placebo	heart failure		Low risk of bias	negative
simvastatin
Hong, 2005	simvastatin	control	heart failure		Risk of bias	negative
Node, 2003	simvastatin	placebo	heart failure			negative
Landmesser, 2005	simvastatin	ezetimibe	heart failure			-
telemonitoring
not classified
TELE-HF, 2010	telemonitoring	control			Risk of bias	-
vasodilators therapy
not classified
Ghose (vs placebo), 1993		placebo			Low risk of bias	negative
VHeFT I (prazosin), 1986	prazosin	placebo			Low risk of bias	-
Colucci, 1980	prazosin	placebo			Exploratory	-
Markham, 1983	prazosin	placebo			Low risk of bias	-
Higginbotham, 1983	prazosin	placebo			Exploratory	-
Ghose (vs captopril) , 1993		captopril			Exploratory	-
V-HeFT II, 1991		enalapril			Low risk of bias	negative
epoprostenol
FIRST, 1997	epoprostenol	standard care			Exploratory	-
hydralazine
Chatterjee, 1980	hydralazine	control			Exploratory	-
Franciosa, 1982	hydralazine	placebo			Low risk of bias	-
Conradson , 1984	hydralazine	placebo			Exploratory	-
Magorien , 1984	hydralazine	placebo			Low risk of bias	-
hydralazine-ISDN
VHeFT I (hydralazine ISDN), 1986	hydralazine-ISDN	placebo			Low risk of bias	negative
isosorbide dinitrate
NICE (Lewis), 1999	isosorbide dinitrate	placebo				-
Franciosa , 1978	isosorbide dinitrate	placebo			Low risk of bias	-
nesiritide
NSGET (comparative trial), 2000	nesiritide	control			Low risk of bias	remark
FUSION 2, 2008        NCT	nesiritide	placebo			Low risk of bias	remark
NSGET (efficacy trial), 2000	nesiritide	placebo			Low risk of bias	negative
PROACTION, 2003	nesiritide	placebo			Low risk of bias	negative
BNP-CARDS, 2007          NCT	nesiritide	placebo			Low risk of bias	remark
ASCEND-HF, 2011        NCT	nesiritide	placebo			Low risk of bias	negative
VMAC (intravenous neseritide), 2002      NCT	nesiritide	placebo			Low risk of bias	remark
PRECEDENT, 2002      NCT	nesiritide	dobutamine			Exploratory	remark
VMAC (24h), 2002      NCT	nesiritide	nitroglycerin			Risk of bias	negative
FUSION 1, 2004    NCT	nesiritide	standard care			Low risk of bias	remark
vasopeptidase inhibitor
omapatrilat
OVERTURE, 2002	omapatrilat	enalapril			Low risk of bias	-
IMPRESS, 2000	omapatrilat	lisinopril			Low risk of bias	suggesting
vasopressin antagonist
tolvaptan
EVEREST Clinical Status , 2007      NCT	tolvaptan	placebo				-
EVEREST Outcome, 2007	tolvaptan	placebo				-
Udelson, 2007      NCT	tovalpan	placebo			Low risk of bias	suggesting