Clinical trials in cardiovascular prevention

Trial	Studied treatment	Control treatment	patients	ROB	Result	NCT
anticoagulant
dicoumarol
Apenstrom and Korsan-Bengtsen, 1964	dicoumarol	no anticoagulant			-
rivaroxaban
COMPASS (rivaroxaban alone), 2017	rivaroxaban	aspirin	secondary prevention		-	NCT01776424
COMPASS (rivaroxaban + aspirin), 2017	rivaroxaban + aspirin	aspirin	secondary prevention	Low risk of bias	-	NCT01776424
wafarin
WARIS, 1990	warfarin	placebo			-
warfarin
Thrombosis Prevention trial (Warfarin), 1998	warfarin	placebo	primary prevention	Low risk of bias	Suggesting	NCT00000614
Thrombosis Prevention trial (W plus A), 1998	warfarin + aspirin	placebo	primary prevention	Exploratory	Suggesting	NCT00000614
antioxydants
beta carotene
SCP beta carotene, 1990	beta carotene	placebo			Negative
ATBC beta carotene, 1994	beta carotene	placebo		Exploratory	-
CARET beta carotene, 1996	beta carotene	placebo		Low risk of bias	Negative
PHS beta carotene, 1996	beta carotene	placebo		Low risk of bias	Suggesting
ATBC 2nd prev subgroup (b carotene), 1998	beta carotene	placebo		Exploratory	Negative
NSCP (Green) beta carotene, 1999	beta carotene	placebo		Low risk of bias	Negative
WHS beta carotene, 1999	beta carotene	placebo		Low risk of bias	Negative	NCT00000479
WACS beta-caroten, 2007	beta carotene	placebo		Low risk of bias	Negative	NCT00000541
vitamin c
WACS vitamin C, 2007	vitamin C	placebo			Negative	NCT00000541
PHS II vitamin C, 2008	vitamin C	placebo		Low risk of bias	Negative	NCT00270647
vitamin e
Linxian, 1993	vitamin E	placebo			Negative
ATBC vitamin E, 1994	vitamin E	placebo		Exploratory	Suggesting
CHAOS, 1996	vitamin E	placebo		Exploratory	Suggesting
ATBC 2nd prev subgroup (vitamin E), 1998	vitamin E	placebo		Exploratory	Negative
GISSI, 1999	vitamin E	control		Risk of bias	Negative
HOPE, 2000	vitamin E	placebo		Low risk of bias	Negative
SPACE, 2000	vitamin E	placebo		Low risk of bias	Suggesting
ASAP, 2000	vitamin E	placebo		Exploratory	Negative
PPP, 2001	vitamin E	control		Risk of bias	Negative
AREDS, 2001	vitamin E	placebo		Exploratory	Negative
HOPE renal insufficiency subgroup, 2004	vitamin E	placebo		Exploratory	Negative
WHS vitamin E, 2005	vitamin E	placebo		Exploratory	Negative	NCT00000479
WACS vitamin E, 2007	vitamin E	placebo		Low risk of bias	Negative	NCT00000541
PHS II vitamin E, 2008	vitamin E	placebo		Low risk of bias	Negative	NCT00270647
antiplatelets drug
aspirin
AAA, 2009	aspirin	placebo	secondary prevention	Low risk of bias	Negative	ISRCTN66587262
clopidogrel
CAPRIE, 1996	clopidogrel	aspirin	secondary prevention	Low risk of bias	Suggesting
CHARISMA, 2006	clopidogrel	placebo (on top aspirin)	secondary prevention	Low risk of bias	Suggesting	NCT00050817
ticagrelor
PEGASUS 60mg, 2015	ticagrelor	placebo (on top aspirin)	secondary prevention	Low risk of bias	Suggesting	NCT01225562
PEGASUS 90mg, 2015	ticagrelor	placebo (on top aspirin)	secondary prevention		Suggesting	NCT01225562
vorapaxar
TRA-2P TIMI 50, 2012	vorapaxar	placebo (on top aspirin)	secondary prevention	Low risk of bias	Suggesting	NCT00526474
TRA-2P TIMI 50 (no prior stroke sub group), 2012	vorapaxar	placebo (on top aspirin)	secondary prevention	Exploratory	Suggesting
TRA-2P TIMI 50 (MI subgroup), 2012	vorapaxar	placebo (on top aspirin)	secondary prevention	Exploratory	Suggesting	NCT00526474
antithrombotics
aspirin
British Doctor’s Trial, 1988	aspirin	no treatment	primary prevention	Risk of bias	Negative
Physicians Health Study, 1989	aspirin	placebo	primary prevention	Low risk of bias	Suggesting	NCT00000500
DAMAD, 1989	aspirin	placebo		Low risk of bias	Negative
PHS (diabetics sub group), 1989	aspirin	placebo		Low risk of bias	Suggesting
ETDRS, 1992	aspirin	placebo		Low risk of bias	Suggesting
Thrombosis Prevention Trial, 1998	aspirin	placebo	primary prevention	Low risk of bias	Suggesting	NCT00000614
HOT, 1998	aspirin	placebo	primary prevention	Low risk of bias	Suggesting
Primary Prevention Project, 2001	aspirin	no treatment	primary prevention	Risk of bias	Negative
PPP (diabetics sub group), 2003	aspirin	no treatment		Exploratory	Negative
Women’s Health Study, 2005	aspirin	placebo	primary prevention	Low risk of bias	Suggesting
WHS (diabetics sub group), 2005	aspirin	placebo		Exploratory	Suggesting
JPAD, 2008	aspirin	no treatment		Risk of bias	Suggesting	NCT00110448
POPADAD aspirin, 2008	aspirin	placebo		Low risk of bias	Negative	ISRCTN53295293
ASPREE, 2018	aspirin	placebo			-	NCT01038583
ASCEND, 2018	aspirin	placebo			Suggesting	NCT00135226
JPPP ongoing	aspirin	no aspirin	primary prevention	Risk of bias	-	NCT00225849
ASCEND (aspirin) ongoing	aspirin	placebo			-	NCT00135226
ACCEPT-D ongoing	aspirin	placebo		Risk of bias	-	ISRCTN48110081
picotamide
Cocozza, 1995	picotamide	placebo		Exploratory	Negative
sulfinpyrazone
Dutch, 1980	sulfinyrazone	placebo			Negative
ticlopidine
Birmingham-A, 1979	ticlopidine	placebo			Negative
London diabetes, 1983	ticlopidine	placebo			Negative
TIMAD, 1984	ticlopidine	placebo			Negative
Nyberg, 1984	ticlopidine	placebo		Low risk of bias	Negative
BTRS, 1992	ticlopidine	placebo			Negative
cholesterol lowering intervention
alirocumab
ODYSSEY OPTIONS I	alirocumab	ezetimibe (on top statin)			Negative
ODYSSEY OPTIONS II	alirocumab	ezetimibe (on top statin)			Negative
ODYSSEY MONO	alirocumab	ezetimibe alone			Negative	NCT01644474
ODYSSEY Alternative	alirocumab	placebo (on top statins)			Negative	NCT01709513
ODYSSEY FH 1	alirocumab	placebo (on top statins)			-	NCT01623115
ODYSSEY FH 2	alirocumab	placebo (on top statins)			-	NCT01709500
ODYSSEY HIGH FH	alirocumab	placebo (on top statins)			Negative	NCT01617655
ODYSSEY COMBO	alirocumab	placebo (on top statins)			Negative	NCT01644175
ODYSSEY COMBO II	alirocumab	placebo (on top statins)			Negative	NCT01644188
ODYSSEY Long-Term, 2015	alirocumab	placebo (on top statins)		Exploratory	Suggesting	NCT01507831
ODYSSEY OUTCOMES, 2018	alirocumab	placebo (on top statins)		Low risk of bias	Conclusive	NCT01663402
CHOICE II ongoing	alirocumab				-	NCT02023879
CHOICE I ongoing	alirocumab				-	NCT01926782
NCT01288469 ongoing	alirocumab				-	NCT01288469
anacetrapib
DEFINE, 2010	anacetrapib	placebo		Exploratory	Negative	NCT00685776
REALIZE, 2015	anacetrapib	placebo			Negative	NCT01524289
atorvastatin
AVERT, 1999	atorvastatin high dose	angioplasty	secondary prevention	Risk of bias	Negative
GREACE, 2002	atorvastatin	usual care	secondary prevention	Risk of bias	Suggesting
ASCOT (diabetics sub group), 2003	atorvastatin	placebo	diabetic patients	Exploratory	Negative
ASCOT, 2003	atorvastatin	placebo	at risk hypertensive	Low risk of bias	Conclusive
Mohler, 2003	atorvastatin	placebo	secondary prevention	Low risk of bias	-
ASCOT (women subgroup) , 2003	Atorvastatin	placebo	women	Exploratory	Negative
CARDS, 2004	atorvastatin	placebo	diabetic	Low risk of bias	Conclusive	NCT00327418
REVERSAL, 2004	atorvastatin high dose	pravastatin	secondary prevention	Exploratory	Negative
PROVE-IT, 2004	atorvastatin high dose	pravastatin	diabetic	Low risk of bias	Suggesting
TNT, 2005	atorvastatin high dose	atorvastatin	secondary prevention	Low risk of bias	Conclusive	NCT00327691
Vascular basis, 2005	atorvastatin high dose	lovastatin	secondary prevention	Exploratory	Negative
Deutsche Diabetes Dialyse Studie (4D), 2005	atorvastatin	placebo		Low risk of bias	Suggesting
IDEAL, 2005	atorvastatin high dose	simvastatin	secondary prevention	Risk of bias	Suggesting	NCT00159835
TNT (diabetic sub group), 2006	atorvastatin high dose	atorvastatin	diabetic patients	Exploratory	Suggesting
ASPEN, 2006	atorvastatin	placebo	diabetic	Low risk of bias	Negative
ASPEN, 2006	atorvastatin	placebo	diabetic patients	Low risk of bias	Negative
ASPEN (primary prevention sub group), 2006	atorvastatin	placebo	diabetic	Exploratory	Negative
SAGE, 2007	atorvastatin high dose	pravastatin	secondary prevention	Exploratory	Suggesting
bezafibrate
BECAIT, 1996	bezafibrate	placebo	secondary prevention	Exploratory	Suggesting
SENDCAP, 1998	bezafibrate	placebo		Exploratory	Suggesting
BIP, 2000	bezafibrate	placebo	secondary prevention	Low risk of bias	Negative
LEADER, 2002	bezafibrate	placebo		Low risk of bias	Negative
bococizumab
SPIRE-1 ongoing	bococizumab	placebo			-	NCT01975376
SPIRE-2 ongoing	bococizumab	placebo			-	NCT01975389
SPIRE-SI ongoing	bococizumab	placebo			-	NCT02135029
SPIRE-HR ongoing	bococizumab	placebo			-	NCT01968954
SPIRE-LDL ongoing	bococizumab	placebo			-	NCT01968967
SPIRE-FH ongoing	bococizumab	placebo			-	NCT01968980
SPIRE-LL ongoing	bococizumab	placebo			-	NCT02100514
cholestyramine
NHLBI (Brensike), 1984	cholestyramine	placebo	diabetic	Exploratory	Negative	NCT00000594
LRC, 1984	cholestyramine	placebo		Low risk of bias	Negative
STARS (cholestyramine), 1992	cholestyramine	control		Low risk of bias	Negative
clofibrate
Harrold, 1969	clofibrate	placebo		Low risk of bias	-
Scottish, 1971	clofibrate	placebo		Low risk of bias	Negative
Newcastle, 1971	clofibrate	placebo		Low risk of bias	Suggesting
Begg, 1971	clofibrate	placebo	secondary prevention	Exploratory	Negative
Acheson, 1972	clofibrate	placebo	secondary prevention	Exploratory	-
VA Neurology Section, 1974	clofibrate	placebo		Low risk of bias	-
Cullen, 1974	clofibrate	placebo		Low risk of bias	-
CDP Clofibrate, 1975	clofibrate	placebo		Low risk of bias	Suggesting
WHO clofibrate, 1978	clofibrate	placebo		Low risk of bias	Suggesting
SCOR, 1990	colestipol+clofibrate	placebo	diabetic	Low risk of bias	Negative
Hanefeld, 1991	clofibrate	placebo		Low risk of bias	Negative
colestipol
Gross, 1973	colestipol	placebo		Low risk of bias	-
Ryan, 1974	colestipol	placebo		Low risk of bias	-
Gundersen, 1976	colestipol	placebo		Exploratory	-
UCS (Dorr), 1978	colestipol	placebo		Low risk of bias	Negative
Ruoff, 1978	colestipol	placebo		Low risk of bias	Negative
diet
Rose, 1965	diet	usual diet		Exploratory	Negative
MRC low fat, 1965	diet	usual diet		Risk of bias	Negative
Woodhill, 1966	diet	usual diet		Low risk of bias	Negative
Oslo Diet Heart Study (Leren), 1966	diet	usual diet		Risk of bias	Suggesting
MRC Soya, 1968	diet	usual diet		Risk of bias	Negative
Veterans Ad. (Dayton), 1969	diet	usual diet		Low risk of bias	Suggesting
Los Angeles VA (Dayton), 1969	diet	usual diet		Risk of bias	-
Minnesota coronary survey (Frantz), 1975	diet	usual diet		Exploratory	Negative
Kallio, 1979	diet	usual diet		Exploratory	-
Hjermann, 1981	diet	usual diet		Risk of bias	-
MRFIT, 1982	diet	usual diet		Risk of bias	-
Finnish Mental Hospital (Miettinen), 1985	diet	usual diet	primary prevention	Exploratory	-
WHO Collaborative, 1986	diet	usual diet		Low risk of bias	Negative
Göteborg (Wilhelmsen), 1986	diet	usual diet		Low risk of bias	Negative
Goteborg, 1986	diet	usual diet		Risk of bias	-
Ornish, 1990	diet	usual diet		Exploratory	Negative
Singh, 1992	diet	usual diet		Risk of bias	-
STARS (St Thomas, diet), 1992	diet	usual diet		Exploratory	Negative
Black, 1994	diet	usual diet		Risk of bias	Negative
WHI low fat, 2005	diet	usual diet		Exploratory	Negative	NCT00000611
Tuttle, 2008	low fat diet	mediterranean-style diet		Risk of bias	-
estrogen
Marmorstein, 1962	estrogen	placebo		Low risk of bias	-
Stamler, 1963	estrogen	placebo		Low risk of bias	-
VA Neurology Section (estrogen), 1966	estrogen	placebo		Low risk of bias	-
VA drugs (Estrogen or thyroxine), 1968	estrogen or thyroxine	placebo		Low risk of bias	Suggesting
CDP estrogen 5, 1975	estrogen	placebo		Low risk of bias	-
CDP estrogen 2.5, 1975	estrogen	placebo		Low risk of bias	-
etofibrate
Emmerich, 2009	etofibrate	placebo	diabetic	Exploratory	-
evolocumab
MENDEl 2	evolocumab				-	NCT01763827
GAUSS 2	evolocumab	ezetimibe alone			Negative	NCT01763905
LAPLACE-TIMI 57	evolocumab	placebo (on top statins)			-	NCT01380730
RUTHERFORD-1	evolocumab	placebo (on top statins)			Negative	NCT01375751
Mendel 1, 2012	evolocumab				-	NCT01375777
GAUSS 1, 2012	evolocumab	placebo			Negative	NCT01375764
YUKAWA-1, 2014	evolocumab				-
DESCARTES, 2014	evolocumab	placebo (on top statins)			Negative	NCT01516879
LAPLACE 2, 2014	evolocumab	placebo (on top statins)			Negative	NCT01763866
RUTHERFORD-2, 2015	evolocumab	placebo (on top statins)			Negative	NCT01763918
FOURIER, 2017	evolocumab	placebo (on top statins)		Low risk of bias	Conclusive	NCT01764633
ezetimibe
Enhance, 2008	ezetimibe	placebo (on top statins)			-
SANDS, 2008	aggressive treatment	standard teatment	diabetic	Exploratory	Negative	NCT00047424
ARBITER-HALTS 6, 2010	ezetimibe	niacin		Exploratory	-
SHARP, 2010	ezetimibe+simvastatin	placebo		Low risk of bias	Suggesting	NCT00125593
IMPROVE-IT, 2014	ezetimibe	placebo (on top statins)			Conclusive	NCT00202878
fenofibrate
DAIS, 2001	fenofibrate	placebo	diabetic	Exploratory	Negative
FIELD, 2005	fenofibrate	placebo	diabetic	Exploratory	Suggesting	ISRCTN64783481
FIELD, 2005	fenofibrate	placebo	diabetic patients	Low risk of bias	Suggesting	ISRCTN64783481
ACCORD lipid, 2010	fenofibrate	placebo (on top simvastatine)	diabetic patients	Low risk of bias	Negative	NCT00000620
fluvastatin
LCAS, 1997	fluvastatin	placebo	secondary prevention	Exploratory	Negative
Riegger et al., 1999	fluvastatin	placebo	secondary prevention	Low risk of bias	Negative
FLARE, 1999	fluvastatin	placebo	secondary prevention	Exploratory	Negative
FLARE (elderly subgroup), 1999	fluvastatin	placebo	elderly	Exploratory	Negative
BCAPS, 2001	fluvastatin	placebo	primary prevention	Exploratory	Negative
LIPS, 2002	fluvastatin	placebo	secondary prevention	Low risk of bias	Suggesting
LIPS (diabetic sub group), 2002	fluvastatin	placebo	diabetic patients	Exploratory	Suggesting
LIPS (elderly subgroup), 2002	fluvastatin	placebo	elderly	Exploratory	Suggesting
ALERT, 2003	fluvastatin	placebo		Low risk of bias	Negative
ALERT (diabetic sub group), 2003	fluvastatin	placebo	diabetic patients	Exploratory	-
ALERT, 2003	fluvastatin	placebo	CKD	Low risk of bias	Suggesting
HYRIM, 2005	fluvastatin	placebo	hypertensive	Exploratory	Negative
gemfibrozil
Helsinki (HHS), 1987	gemfibrozil	placebo		Low risk of bias	Suggesting
HHS (diabetic sub group), 1987	gemfibrozil	placebo	diabetic patients	Exploratory	-
HHS (Frick)(secondary prev subgroup), 1993	gemfibrozil	placebo		Exploratory	Negative
LOCAT, 1997	gemfibrozil	placebo		Exploratory	Negative
VA-HIT, 1999	gemfibrozil	placebo		Low risk of bias	Suggesting	NCT00283335
VA-HIT (diabetic sub group), 1999	gemfibrozil	placebo	diabetic patients	Exploratory	Negative
lovastatin
Excel, 1991	lovastatin	placebo		Exploratory	Negative
Sahni, 1991	lovastatin	usual care	secondary prevention	Risk of bias	Negative
MARS, 1993	lovastatin	placebo	secondary prevention	Exploratory	Negative	NCT00116870
CCAIT, 1994	lovastatin	placebo	secondary prevention	Exploratory	Negative
Weintraub, 1994	lovastatin	placebo	secondary prevention	Low risk of bias	Negative
CRISP 20mg, 1994	lovastatin	placebo	diabetic	Exploratory	-	NCT00000477
ACAPS, 1994	lovastatin	placebo	secondary prevention	Exploratory	Suggesting	NCT00000469
CRISP 40mg, 1994	lovastatin	placebo	diabetic	Exploratory	-	NCT00000477
AFCAPS/TexCAPS, 1998	lovastatin	placebo	primary prevention	Low risk of bias	Conclusive
AFCAPS/TexCAPS (diabetic sub group), 1998	lovastatin	placebo	diabetic patients	Exploratory	-
AFCAPS (women subgroup) , 1998	Lovastatin	placebo	women	Exploratory	Negative
CLAPT, 1999	lovastatin	usual care	secondary prevention	Exploratory	Negative
niacin
VA drugs, 1968	niacin	control		Low risk of bias	Negative
CDP niacin, 1975	niacin	placebo		Low risk of bias	Suggesting
Carlson (Stockholm), 1977	clofibtate+niacin	placebo	secondary prevention	Risk of bias	Suggesting
CLAS, 1987	colestipol-niacin	placebo	secondary prevention	Exploratory	Negative
pactimibe
ACTIVATE, 2006	pactimibe	placebo		Exploratory	-	NCT00185042
CAPTIVATE, 2009	pactimibe	placebo		Exploratory	-	NCT00151788
policosanol
Batista, 1996	policosanol	control		Low risk of bias	-
Más, 1999	policosanol	control		Exploratory	Negative
Castano, 2001	policosanol	control	diabetic	Exploratory	Negative
pravastatin
PMSG, 1993	pravastatin	placebo	primary prevention	Exploratory	Negative
PLAC I, 1995	pravastatin	placebo	secondary prevention	Exploratory	Suggesting
PLAC II, 1995	pravastatin	placebo	secondary prevention	Exploratory	Negative
KAPS, 1995	pravastatin	placebo	primary prevention	Exploratory	Negative
WOSCOPS, 1995	pravastatin	placebo	primary prevention	Low risk of bias	Conclusive
REGRESS, 1995	pravastatin	placebo	secondary prevention	Exploratory	Suggesting
PLAC I (elderly sub group), 1995	Pravastatin	placebo	elderly	Exploratory	Negative
REGRESS (elderly subgroup), 1995	Pravastatin	placebo	elderly	Exploratory	Negative
WOSCOPS (diabetic sub group), 1996	pravastatin	placebo	diabetic patients	Exploratory	-
CARE, 1996	pravastatin	placebo	secondary prevention	Low risk of bias	Conclusive
CAIUS, 1996	pravastatin	placebo	primary prevention	Exploratory	Negative
LIPID (diabetic sub group), 1998	pravastatin	placebo	diabetic patients	Exploratory	Negative
CARE (diabetic sub group), 1998	pravastatin	placebo	diabetic patients	Exploratory	Suggesting
LIPID, 1998	pravastatin	placebo	secondary prevention	Low risk of bias	Conclusive
CARE (elderly subgroup), 1998	Pravastatin	placebo	elderly	Exploratory	Suggesting
GISSI P (diabetic sub group), 2000	pravastatin	usual care	diabetic patients	Exploratory	-
KLIS, 2000	pravastatin	usual care	primary prevention	Risk of bias	-
GISSI Prevenzione, 2000	pravastatin	usual care	secondary prevention	Risk of bias	Negative
LIPID (elderly sub group), 2001	Pravastatin	placebo	elderly	Exploratory	Suggesting
FAST Fukuoka pravastatin, 2002	pravastatin	control	primary prevention	Exploratory	-
PROSPER diabetic (sub group), 2002	pravastatin	placebo	diabetic patients	Exploratory	Negative
PROSPER, 2002	pravastatin	placebo	secondary prevention	Low risk of bias	Conclusive
PROSPER (primary prevention subgroup), 2002	pravastatin	placebo	primary prevention	Exploratory	Negative
ALLHAT (women subgroup) , 2002	Pravastatin	placebo	women	Exploratory	Negative
ALLHAT, 2002	pravastatin	usual care	at risk hypertensive	Risk of bias	Negative	NCT00000542
ALLHAT-LLT (diabetic sub group), 2002	pravastatin	usual care	diabetic patients	Exploratory	Negative
PACT, 2004	pravastatin	placebo	secondary prevention	Low risk of bias	Negative
PHYLLIS, 2004	pravastatin	placebo	diabetic	Exploratory	-
PREVEND IT, 2004	pravastatin	placebo	related disease	Low risk of bias	Negative
MEGA, 2006	pravastatin	control	primary prevention	Risk of bias	Suggesting	NCT00211705
MEGA (women subgroup) , 2006	Pravastatin	placebo	women	Exploratory	Suggesting
PROVE IT TIMI 22 (diabetic sub group), 2006	pravastatin high dose	pravastatin	diabetic patients	Exploratory	-
probucol
McCaughan, 1981	Probucol	placebo		Exploratory	-
PQRST, 1994	probucol	placebo		Exploratory	-
Tardif, 1997	Probucol	placebo		Low risk of bias	Negative
FATS Fukosawa (probucol), 2002	probucol	control	primary prevention	Exploratory	-
rosuvastatin
METEOR, 2007	rosuvastatin	placebo	diabetic	Exploratory	Negative	NCT00225589
JUPITER, 2008	rosuvastatin	placebo	primary prevention	Low risk of bias	Conclusive	NCT00239681
JUPITER (women subgroup) , 2008	Rosuvastatin	placebo	women	Exploratory	Suggesting
AURORA, 2009	rosuvastatin	placebo		Low risk of bias	Negative
JUPITER (elderly sub group), 2009	rosuvastatin	placebo	elderly	Exploratory	Suggesting
HOPE 3, 2016	rosuvastatin	placebo	primary prevention	Low risk of bias	Conclusive	NCT00468923
ASTEROID ongoing	Rosuvastatin	control			-
simvastatin
MAAS, 1994	simvastatin	placebo	secondary prevention	Exploratory	Negative
4S, 1994	simvastatin	placebo	secondary prevention	Low risk of bias	Conclusive
CIS, 1997	simvastatin	placebo	secondary prevention	Exploratory	Negative
4S (elderly subgroup), 1997	simvastatin	placebo	elderly	Exploratory	Suggesting
4S (diabetic sub group), 1999	simvastatin	placebo	diabetic patients	Exploratory	Suggesting
HPS (diabetic sub group), 2002	simvastatin	placebo	diabetic patients	Exploratory	Suggesting
HPS, 2002	simvastatin	placebo	secondary prevention	Low risk of bias	Conclusive
HPS (elderly subgroup), 2002	simvastatin	placebo	elderly	Exploratory	Suggesting
HPS (women subgroup) , 2002	Simvastatin	placebo	women	Exploratory	Suggesting
HPS (diabetic primary prevention sub group), 2003	simvastatin	placebo	diabetic	Exploratory	-
SEARCH, 2010	simvastatin high dose	simvastatin	secondary prevention	Low risk of bias	Suggesting	NCT00124072
thyroxine
CDP tyroxine, 1975	thyroxine	placebo		Low risk of bias	-
torcetrapib
RADIANCE 1, 2007	torcetrapib	placebo		Exploratory	Negative	NCT00136981
ILLUMINATE, 2007	torcetrapib	placebo			Negative	NCT00134264
RADIANCE 2, 2007	torcetrapib	placebo		Exploratory	-
ILLUSTRATE, 2007	torcetrapib	placebo		Exploratory	Negative	NCT00134173
hormonal replacement therapy
estrogen
HERS, 1998	combined estrogen and progestogen	placebo		Low risk of bias	Negative	NCT00319566
Hall, 1998	combined estrogen and progestogen	placebo		Exploratory	Negative
ERA (estrogen alone ), 2000	estrogen	placebo		Exploratory	Negative	NCT00000549
EVTET, 2000	combined estrogen and progestogen	placebo		Low risk of bias	Negative
ERA (estrogen plus medroxyprogesterone), 2000	combined estrogen and progestogen	placebo		Exploratory	Negative	NCT00000549
EPAT, 2001	estrogen	placebo		Exploratory	Negative
WEST, 2001	estrogen	placebo		Low risk of bias	Negative
WAVE, 2002	combined estrogen and progestogen	placebo		Exploratory	Negative	NCT00000555
Schulman (NHLBI) (estrogen alone), 2002	estrogen	placebo		Exploratory	-	NCT00000601
ESPRIT, 2002	estrogen	placebo		Low risk of bias	Negative
WHI, 2002	combined estrogen and progestogen	placebo		Low risk of bias	Negative
Schulman (NHLBI) (estrogen-progestogen), 2002	combined estrogen and progestogen	placebo			-	NCT00000601
WELL-HART (estrogen alone), 2003	estrogen	placebo		Exploratory	Negative	NCT00000559
WELL-HART (estrogen-progestin), 2003	combined estrogen and progestogen	placebo		Exploratory	Negative	NCT00000559
EAGAR, 2006	combined estrogen and progestogen	placebo		Exploratory	Negative	NCT00000605
WHISP, 2006	combined estrogen and progestogen	placebo		Exploratory	Negative
WISDOM, 2007	combined estrogen and progestogen	placebo		Low risk of bias	Negative	ISRCTN63718836
inhibition of the renin-angiotensin system (ACEI or ARB)
enalapril
CAMELOT (enalapril), 2004	enalapril	placebo			Negative
perindopril
EUROPA, 2003	perindopril	placebo			Suggesting
quinapril
QUIET, 2001	quinapril	placebo			Negative
ramipril
HOPE, 2000	ramipril	placebo			Suggesting
ONTARGET (association vs ramipril), 2008	telmisartan + ramipril	ramipril			Negative	NCT00153101
ONTARGET (association vs telmisartan), 2008	telmisartan + ramipril	telmisartan			Suggesting	NCT00153101
telmisartan
TRANSCEND, 2008	telmisartan	placebo		Low risk of bias	Suggesting	NCT00153101
ONTARGET (telmisartan alone), 2008	telmisartan	ramipril		Low risk of bias	Suggesting	NCT00153101
trandolapril
PEACE, 2004	trandolapril	placebo			Suggesting	NCT00000558
niacin
niacin
HPS 2-Thrive	niacin	placebo (on top statin)		Low risk of bias	Negative	NCT00461630
HATS, 2001	niacin	placebo (on top statin)		Risk of bias	Negative
ARBITER 6-HALTS (niacin vs ezetimibe), 2009	niacin	ezetimibe		Exploratory	Suggesting	NCT00397657
Oxford Niaspan Study, 2009	niacin	placebo (on top statin)		Exploratory	-	NCT00232531
ARBITER 2, 2009	niacin	placebo (on top statin)		Exploratory	Negative
AIM-HIGH, 2011	niacin	placebo (on top statin)		Low risk of bias	Negative	NCT00120289
omega-3 fatty acids
diet
Burr (DART), 1989	diet	control			Suggesting
Mate-Jimenez, 1991	diet	control		Exploratory	-
Burr (DART 2), 2003	diet	control			Negative
fish oil
Borchgrevink, 1966	fish oil	placebo			Negative
Dry, 1991	fish oil	placebo		Exploratory	-
Franzen, 1993	fish oil	control		Exploratory	-
Geusens, 1994	fish oil	placebo		Exploratory	-
Leaf, 1994	fish oil	placebo			Negative
Sacks (TOHP 1), 1994	fish oil	placebo			-	NCT00000528
Shimizu, 1995	fish oil	control		Exploratory	-
Loeschke, 1996	fish oil	placebo		Exploratory	Negative
Lorenz-Meyer, 1996	fish oil	placebo		Exploratory	-
Katan, 1997	fish oil	control		Exploratory	-
Almallah, 1998	fish oil	placebo		Exploratory	-
Malaguarnera, 1999	fish oil	control		Exploratory	Negative
Terano, 1999	fish oil	control		Exploratory	Negative
von Schacky, 1999	fish oil	placebo			Negative
Brox, 2001	fish oil	control		Exploratory	Negative
Bemelmans, 2002	fish oil	control		Exploratory	Negative
omacor
Eritsland, 1996	Omacor	control			Negative
GISSI-P, 1999	Omacor	control		Risk of bias	Suggesting
Johansen, 1999	Omacor	placebo			Negative
Nilsen, 2001	Omacor	placebo			Negative
plasma homocysteine lowering intervention
folic acid
SU.FOL.OM3	folic acid, vit B12 and vit B6	placebo			Negative	ISRCTN41926726
CHAOS-2, 2002	folic acid	placebo			Negative
GOES (Liem), 2003	folic acid	control		Risk of bias	Negative
FOLARDA (Liem), 2004	folic acid	control		Exploratory	Negative
VISP (Toole), 2004	high dose - folic acid, vit B12 and vit B6	low dose - folic acid, vit B12 and vit B6		Low risk of bias	Negative
NORVIT (folic acid + B12) (Bonaa), 2006	folic acid, B12	control		Low risk of bias	Negative	NCT00266487
NORVIT (folic acid, B12 and vit B6) (Bonaa), 2006	folic acid, vit B12 and vit B6	control		Low risk of bias	Negative	NCT00266487
HOPE-2 (Lonn), 2006	folic acid, vit B12 and vit B6	placebo		Low risk of bias	Suggesting	NCT00106886
SEARCH, 2007	folic acid, B12	placebo		Low risk of bias	Negative	NCT00124072
WAFACS, 2008	folic acid, vit B12 and vit B6	placebo		Low risk of bias	Negative	NCT00000541
WENBIT (folic ac,B12), 2008	folic acid, B12	placebo		Low risk of bias	Negative	NCT00354081
CSPPT, 2015	folic acid	placebo		Low risk of bias	Suggesting	NCT00794885

cardiovascular prevention Description Results

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cardiovascular prevention
Description Results