cardiovascular prevention

systematic review meta-analysis network meta-analysis

Select weight-loss drugscholesterol lowering interventionniacinPCSK9 Inhibitorsstatinsanticoagulantantiplatelets drugantithromboticsdirect factor Xa inhibitorsdirect oral anticoagulant (DAO)HDL increasing drugsACAT inhibitionantioxydantsCEPT inhibitiondietdietary salt reductionhormonal replacement therapylifestyle interventionomega-3 fatty acids on top statinsplasma homocysteine lowering interventionpolypill all chronical situationsAll type of patientDiabetic patientselderly patientshigh risk patients with or without LDL cholesterol elevationoverweight or obese patientspatients at low riskpatient with related diseasepatients at high riskPatients with LDL elevation and without CHDpatients with other atherosclerotic localisationpatients with prior MI or with CHDpatients undergoing dialysisuncoded clinical condition ***post stroke (or TIA)primary preventionsecondary prevention in patients with CADsecondary preventionsecondary prevention in patients with intermittent claudicationwomen       ACAT inhibitionanticoagulantantioxydantaspirinCETP inhibitorclopidogrelcolestipol-niacincombination therapiesdietdipyridamolendocannabinoid receptor ezetimibefibrateshormonal replacement therapyhormonesinhibitor of lipoprotein-associated phospholipaseMediterranean dietMultiple risk factor interventionsniacinniacin (on top statin)niacin in associationNOAComega-3 Fatty acidsother cholesterol lowering drugsP2Y12 receptor-antagonistPCSK9 Inhibitorplasma homocysteine lowering interventionplatelet aggregation inhibitorsPolicosanolpolypillProbucolresinsrimonabant selective PAR-1 thrombin receptor antagonistsodium reductionstatinsstatins high dosestatins+ezetimibestrategysurgeryticlopidineVKAVKA + antiplatelet atorvastatincerivastatinfluvastatinlovastatinpravastatinrosuvastatinsimvastatinezetimibebezafibratefenofibratepolicosanolvariouswafarinalirocumabanacetrapibaspirinbeta carotenebococizumabcholestyramineclofibrateclopidogrelcolestipoldicoumaroldietdipyridamolestrogenetofibrateevolocumab fish oilfolic acidgemfibrozilketanserineniacinomacorpactimibepicotamideprobucolrimonabantrivaroxabansulfinpyrazonesuloctidilthyroxineticagrelorticlopidinetorcetrapibvitamin cvitamin evorapaxarwarfarin vs controlvs placebovs placebo or controlvs active treatmentvs angioplastyvs aspirinvs ezetimibevs folic acid, vit B12 and vit B6vs statin       cerebral vascular diseaseearly initiationelderlyhypertensive patientskidney diseasesprimary preventionsecondary preventionsquamous NSCLCtype 2 diabetes

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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 (646)cardiovascular events (360)stroke (fatal and non fatal) (314)Non fatal MI (295)Coronary event (293)Coronary death (273)Cardiovascular death (254)non cardiovascular death (250)cardiac death (194)Rhabdomyolysis (79)Fatal stroke (78)Non fatal stroke (74)Death from cancer (73)Haemmorhagic stroke (71)Coronary death and non fatal MI (64)MACE (63)myocardial infarction (fatal and non fatal) (53)new-onset diabetes (48)ischemic stroke (46)Cancer (41)Fatal MI (38)Myopathy (34)Fatal bleeding (33)Venous thromboembolism (28)Vascular death (27)Adverse events (24)Major bleeding (24)Vascular events (23)Revascularization (23)Major gastrointestinal bleeding (18)Smoking prevalence (16)Non cerebral major bleeding (15)serious adverse events (15)death from all causes as adverse event (14)blood cholesterol concentration (12)puylmonary embolism (12)DBP change from baseline (mmHg) (11)intracranial hemorrhage (11)cardiovascular death, MI, stroke (11)cardiovascular events at 4 months (10)cardiovascular events at 1 month (10)SBP change from baseline (mmHG) (10)Gastrointestinal Bleeding (9)cardiovascular death as adverse event (8)Coronary revascularization (8)Non vascular death (8)Long term death (7)Amputation (7)Peptic ulcer (6)cardiovascular events including revascularization (6)Peripheral vascular events (5)stable angina (5)weight loss equal to or greater than 10 percent (5)long term cardiovascular events (5)Sudden death (4)cardiovascular events as adverse event (4)Neurocognitive disorder (4)fatal hemorrhagic stroke (4)non fatal hemorrhagic stroke (3)Hematuria (3)myocardial infarction as adverse event (3)Muscle-related adverse events (3)total cholesterol (at 1 y) (2)HDL (at 1 y) (2)LDL (2)End stage renal disease (2)unstable angina (2)TIA (2)weight loss equal to or greater than 5 percent (2)stroke or TIA (2)long term cardiovascular death (2)recurrent angina (2)CABG (2)PTCA (1)Deaths or MI (1)target lesion revascularisation (1)vision loss (1)retinopathy (1)Waist circumference change from baseline (cm) (1)Fasting glucose change (mmol/liter) (1)weight change from baseline (kg) (1)new-onset atrial fibrillation (1)neurological SAE (1)Allergic reactions (1)net benefit (1) Options Numeric bar chart forest plot medians
Trial	Studied trt	Control trt	patients	tags	ROB	Trial result	All cause death	cardiovascular events
ACAT inhibition
pactimibe
CAPTIVATE, 2009      NCT	pactimibe	placebo			Low risk of bias	-
ACTIVATE, 2006      NCT	pactimibe	placebo			Low risk of bias	-
anticoagulant
not classified
MacMillan, 1960	anticoagulant	no anticoagulant				-
Borchegrevink, 1960	anticoagulant	no anticoagulant				-
Clausen, 1961	anticoagulant	no anticoagulant				-
Harvald, 1961	anticoagulant	no anticoagulant				-
Conrad, 1964	anticoagulant	no anticoagulant				-
Wasserman, 1966	anticoagulant	no anticoagulant				-
Loeliger, 1967	anticoagulant	no anticoagulant				-
Lovell, 1967	anticoagulant	no anticoagulant				-
Seaman, 1969	anticoagulant	no anticoagulant				-
Sorensen, 1969	anticoagulant	no anticoagulant				-
Meuwisse,, 1969	anticoagulant	no anticoagulant				-
Drapkin and Merskey, 1972	anticoagulant	no anticoagulant				-
Sixty Plus Reinfarction, 1980	coumarin congeners	placebo			Low risk of bias	-
ASPECT, 1994	nicoumalone or phenprocoumon	placebo				-
Breddin, 1980	phenprocoumon	placebo			Low risk of bias	-
dicoumarol
Apenstrom and Korsan-Bengtsen, 1964	dicoumarol	no anticoagulant				-
rivaroxaban
COMPASS (rivaroxaban alone), 2017    NCT	rivaroxaban	aspirin	secondary prevention			-
COMPASS (rivaroxaban + aspirin), 2017      NCT	rivaroxaban + aspirin	aspirin	secondary prevention		Low risk of bias	-
wafarin
WARIS, 1990	warfarin	placebo			Low risk of bias	-
warfarin
Thrombosis Prevention trial (Warfarin), 1998        NCT	warfarin	placebo	primary prevention		Low risk of bias	suggesting
Thrombosis Prevention trial (W plus A), 1998        NCT	warfarin + aspirin	placebo	primary prevention		Low risk of bias	suggesting
antioxydants
not classified
Tepel, 2003	acetylcysteine	placebo			Low risk of bias	suggesting
HPS antioxidant, 2002	combination	placebo			Low risk of bias	negative
WAVE (Waters), 2002	combination	placebo			Low risk of bias	negative
POPADAD (antioxydant), 2008	combination	placebo			Low risk of bias	negative
PHS II beta carotene, 2003          NCT	combination	placebo			Low risk of bias	-
SUVIMAX, 2005	combination	placebo			Low risk of bias	negative
HATS, 2001	combination	placebo			Low risk of bias	negative
MVP, 1997	combination	placebo			Low risk of bias	negative
PHS II (multivitamin), 2012        NCT	combination	placebo			Low risk of bias	negative
ARISE, 2008      NCT	succinobucol	placebo			Low risk of bias	suggesting
beta carotene
ATBC beta carotene, 1994	beta carotene	placebo			Low risk of bias	-
CARET beta carotene, 1996	beta carotene	placebo			Low risk of bias	negative
SCP beta carotene, 1990	beta carotene	placebo			Low risk of bias	negative
NSCP (Green) beta carotene, 1999	beta carotene	placebo			Low risk of bias	negative
PHS beta carotene, 1996	beta carotene	placebo			Low risk of bias	suggesting
WHS beta carotene, 1999        NCT	beta carotene	placebo			Low risk of bias	negative
WACS beta-caroten, 2007        NCT	beta carotene	placebo			Low risk of bias	negative
ATBC 2nd prev subgroup (b carotene), 1998	beta carotene	placebo			Low risk of bias	negative
vitamin c
WACS vitamin C, 2007        NCT	vitamin C	placebo			Low risk of bias	negative
PHS II vitamin C, 2008    NCT	vitamin C	placebo			Low risk of bias	negative
vitamin e
GISSI, 1999	vitamin E	control			Risk of bias	negative
PPP, 2001	vitamin E	control			Risk of bias	negative
ATBC vitamin E, 1994	vitamin E	placebo			Low risk of bias	suggesting
CHAOS, 1996	vitamin E	placebo			Low risk of bias	suggesting
HOPE, 2000	vitamin E	placebo			Low risk of bias	negative
AREDS, 2001	vitamin E	placebo			Low risk of bias	negative
Linxian, 1993	vitamin E	placebo				negative
WACS vitamin E, 2007        NCT	vitamin E	placebo			Low risk of bias	negative
PHS II vitamin E, 2008    NCT	vitamin E	placebo			Low risk of bias	negative
WHS vitamin E, 2005      NCT	vitamin E	placebo			Low risk of bias	negative
ASAP, 2000	vitamin E	placebo			Low risk of bias	negative
SPACE, 2000	vitamin E	placebo			Low risk of bias	suggesting
HOPE renal insufficiency subgroup, 2004	vitamin E	placebo			Low risk of bias	negative
ATBC 2nd prev subgroup (vitamin E), 1998	vitamin E	placebo			Low risk of bias	negative
antiplatelets drug
aspirin
JPAD, 2008      NCT	aspirin	no treatment			Risk of bias	suggesting
PPP (diabetics sub group), 2003	aspirin	no treatment			Exploratory	negative
British Doctor’s Trial, 1988	aspirin	no treatment	primary prevention		Risk of bias	negative
Primary Prevention Project, 2001	aspirin	no treatment	primary prevention		Risk of bias	negative
POPADAD aspirin, 2008	aspirin	placebo			Low risk of bias	negative
DAMAD, 1989	aspirin	placebo			Low risk of bias	negative
ETDRS, 1992	aspirin	placebo			Low risk of bias	suggesting
PHS (diabetics sub group), 1989	aspirin	placebo			Low risk of bias	suggesting
WHS (diabetics sub group), 2005	aspirin	placebo			Low risk of bias	suggesting
Physicians Health Study, 1989    NCT	aspirin	placebo	primary prevention		Low risk of bias	suggesting
Thrombosis Prevention Trial, 1998        NCT	aspirin	placebo	primary prevention		Low risk of bias	suggesting
HOT, 1998	aspirin	placebo	primary prevention		Low risk of bias	suggesting
Women’s Health Study, 2005	aspirin	placebo	primary prevention		Low risk of bias	suggesting
AAA, 2009	aspirin	placebo	secondary prevention		Low risk of bias	negative
ASPREE, 2018    NCT	aspirin	placebo				-
ASCEND, 2018      NCT	aspirin	placebo				suggesting
Schoop, 1983	aspirin	placebo			Low risk of bias	-
Hess, 1985	aspirin	placebo				-
Munich A, 1975	aspirin	placebo			Low risk of bias	-
Munich B, 1975	aspirin	placebo			Low risk of bias	-
CLIPS, 2007	aspirin	placebo			Low risk of bias	suggesting
CDPA, 1976	aspirin	placebo			Low risk of bias	negative
Cardiff I, 1974	aspirin	placebo			Low risk of bias	negative
Cardiff II, 1979	aspirin	placebo			Low risk of bias	negative
Vogel, 1979	aspirin	placebo			Low risk of bias	suggesting
AMIS, 1980    NCT	aspirin	placebo			Low risk of bias	suggesting
GAMIS, 1980	aspirin	placebo			Low risk of bias	negative
PARIS, 1980	aspirin	placebo			Low risk of bias	negative
JAMIS, 1999	aspirin	placebo				suggesting
SAPAT, 1992	aspirin	placebo			Low risk of bias	suggesting
clopidogrel
CAPRIE, 1996	clopidogrel	aspirin	secondary prevention		Low risk of bias	suggesting
CAPRIE (PAD subgroup), 1996	clopidogrel	aspirin			Low risk of bias	suggesting
ASCET    NCT	clopidogrel	aspirin			Risk of bias	negative
CHARISMA, 2006      NCT	clopidogrel	placebo (on top aspirin)	secondary prevention		Low risk of bias	suggesting
dipyridamol
Atlanta (Sbar), 1967	dipyridamol	control			Low risk of bias	negative
Becker, 1967	dipyridamol	control			Low risk of bias	negative
Wirecki, 1967	dipyridamol	control			Low risk of bias	negative
Hess (2), 1985	aspirin + dipyridamol	placebo			Low risk of bias	-
Schoop (2), 1983	aspirin + dipyridamol	placebo			Low risk of bias	-
VA study, 1986	aspirin + dipyridamol	placebo			Low risk of bias	-
Igloe, 1970	dipyridamol	placebo			Low risk of bias	-
Zion, 1961	dipyridamol	placebo			Low risk of bias	-
Kinsella, 1962	dipyridamol	placebo			Low risk of bias	-
Leiberman, 1964	dipyridamol	placebo			Low risk of bias	-
Dewar, 1961	dipyridamol	placebo			Low risk of bias	-
Neumann, 1964	dipyridamol	placebo			Low risk of bias	-
Foulds, 1960	dipyridamol	placebo			Low risk of bias	-
PARIS, 1980	dipyridamol + aspirin	placebo			Low risk of bias	negative
PARIS-II, 1986	dipyridamol + aspirin	placebo			Low risk of bias	negative
PARIS, 1980	dipyridamol + aspirin	aspirin			Low risk of bias	negative
ketanserine
PACK, 1996	ketanserine	placebo			Low risk of bias	-
Walden, 1991	ketanserine	placebo			Low risk of bias	-
Thulesius, 1987	ketanserine	placebo			Low risk of bias	-
picotamide
Cocozza, 1995	picotamide	placebo			Low risk of bias	negative
ADEP, 1993	picotamide	placebo			Low risk of bias	-
Neirotti, 1994	picotamide	placebo			Low risk of bias	-
Coto, 1989	picotamide	placebo			Low risk of bias	-
sulfinpyrazone
Dutch, 1980	sulfinyrazone	placebo				negative
suloctidil
Adriaensen, 1976	suloctidil	placebo			Low risk of bias	-
Verhaeghe, 1981	suloctidil	placebo			Low risk of bias	-
Jones, 1982	suloctidil	placebo			Low risk of bias	-
Holm, 1984	suloctidil	placebo			Low risk of bias	-
ticagrelor
EUCLID, 2016        NCT	ticagrelor	clopidogrel			Low risk of bias	-
PEGASUS 60mg, 2015        NCT	ticagrelor	placebo (on top aspirin)	secondary prevention		Low risk of bias	suggesting
PEGASUS 90mg, 2015        NCT	ticagrelor	placebo (on top aspirin)	secondary prevention		Low risk of bias	suggesting
ticlopidine
Birmingham-A, 1979	ticlopidine	placebo				negative
London diabetes, 1983	ticlopidine	placebo				negative
TIMAD, 1984	ticlopidine	placebo				negative
BTRS, 1992	ticlopidine	placebo			Low risk of bias	negative
Nyberg, 1984	ticlopidine	placebo			Low risk of bias	negative
EMATAP, 1993	ticlopidine	placebo			Low risk of bias	-
Katsumara, 1982	ticlopidine	placebo			Low risk of bias	-
Aukland, 1982	ticlopidine	placebo			Low risk of bias	-
Stiegler, 1984	ticlopidine	placebo			Low risk of bias	-
Ellis, 1986	ticlopidine	placebo			Low risk of bias	-
Cloarec, 1986	ticlopidine	placebo			Low risk of bias	-
Arcan, 1988	ticlopidine	placebo			Low risk of bias	-
Balsano, 1989	ticlopidine	placebo			Low risk of bias	-
STIMS, 1990	ticlopidine	placebo			Low risk of bias	-
Hurlow, 1980	ticlopidine	placebo			Low risk of bias	-
Krause, 1980	ticlopidine	placebo			Low risk of bias	-
Berglund, 1985	ticlopidine	placebo			Low risk of bias	negative
various
CRAMPS, 2000	cloricromene	placebo			Low risk of bias	-
vorapaxar
TRA-2P TIMI 50, 2012        NCT	vorapaxar	placebo (on top aspirin)	secondary prevention		Low risk of bias	suggesting
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        NCT	vorapaxar	placebo (on top aspirin)	secondary prevention		Exploratory	suggesting
CEPT inhibition
not classified
REVEAL HPS-3 TIMI-55, 2017    NCT	anacetrapib	placebo			Low risk of bias	remark
dal-VESSEL, 2011	dalcetrapib	placebo			Exploratory	-
dal-OUTCOMES, 2012      NCT	dalcetrapib	placebo			Low risk of bias	negative
ACCELERATE, 2017      NCT	evacetrapib	placebo			Low risk of bias	suggesting
anacetrapib
DEFINE, 2010    NCT	anacetrapib	placebo			Exploratory	negative
REALIZE, 2015      NCT	anacetrapib	placebo			Low risk of bias	negative
torcetrapib
RADIANCE 1, 2007      NCT	torcetrapib	placebo			Exploratory	negative
ILLUMINATE, 2007      NCT	torcetrapib	placebo			Low risk of bias	negative
RADIANCE 2, 2007	torcetrapib	placebo			Low risk of bias	-
ILLUSTRATE, 2007      NCT	torcetrapib	placebo			Exploratory	negative
cholesterol lowering intervention
not classified
FACS, 2010			acute coronary syndrome	early initiation		-
Shalnev VI, 2007			acute coronary syndrome	early initiation		-
FATS, 1990    NCT	intensive lipid-lowering therapy	diet	primary prevention		Exploratory	negative
Sakamoto, 2006	any statin	no statin	acute coronary syndrome	early initiation	Risk of bias	-
POSCH, 1990      NCT	partial ileum bypass surgery	no surgery			Risk of bias	negative
SOLID-TIMI 52      NCT	darapladib	placebo	acute coronary syndrome	early initiation		-
Ren, 2009	simvastatin	placebo	acute coronary syndrome	early initiation	Low risk of bias	-
HARP, 1994    NCT	various drugs	placebo			Exploratory	negative
OACIS-LIPID, 2008	pravastatin	usual care	acute coronary syndrome	early initiation	Low risk of bias	-
SCRIP, 1994    NCT	various drugs	usual care			Exploratory	negative
JAPAN ACS, 2009      NCT	pitavastatin	atorvastatin	acute coronary syndrome	early initiation	Exploratory	-
Post CABG (diabetic sub group), 1999	aggressive cholesterol-lowering	moderate cholesterol-lowering	diabetic patients	secondary prevention	Low risk of bias	-
atorvastatin
ASCOT (diabetics sub group), 2003	atorvastatin	placebo	diabetic patients	primary prevention	Exploratory	negative
CARDS, 2004      NCT	atorvastatin	placebo	diabetic	type 2 diabetes	Low risk of bias	conclusive
Deutsche Diabetes Dialyse Studie (4D), 2005	atorvastatin	placebo			Low risk of bias	suggesting
ASPEN, 2006	atorvastatin	placebo	diabetic	type 2 diabetes	Low risk of bias	negative
ASPEN, 2006	atorvastatin	placebo	diabetic patients		Low risk of bias	negative
ASCOT, 2003	atorvastatin	placebo	at risk hypertensive	hypertensive patients	Low risk of bias	conclusive
MIRACL, 2001	atorvastatin	placebo	acute coronary syndrome	early initiation	Low risk of bias	suggesting
macin, 2005	atorvastatin	placebo	acute coronary syndrome	squamous NSCLC	Low risk of bias	-
SALTIRE, 2005	atorvastatin	placebo	aortic stenosis		Low risk of bias	negative
Mohler III, 2003	atorvastatin	placebo	Peripheral Arterial Disease		Exploratory	-
SPARCL, 2006      NCT	atorvastatin	placebo	post stroke	cerebral vascular disease	Low risk of bias	suggesting
Strey, 2005	atorvastatin	placebo	heart failure			-
Mohler, 2003	atorvastatin	placebo	secondary prevention		Low risk of bias	-
ASPEN (primary prevention sub group), 2006	atorvastatin	placebo	diabetic	type 2 diabetes	Low risk of bias	negative
ASCOT (women subgroup) , 2003	Atorvastatin	placebo	women		Exploratory	negative
Colivicchi, 2002	atorvastatin	usual care	acute coronary syndrome	early initiation	Exploratory	negative
ESTABLISH, 2004	atorvastatin	usual care	acute coronary syndrome	early initiation	Exploratory	negative
GREACE, 2002	atorvastatin	usual care	secondary prevention		Risk of bias	suggesting
AVERT, 1999	atorvastatin high dose	angioplasty	secondary prevention		Risk of bias	negative
TNT (diabetic sub group), 2006	atorvastatin high dose	atorvastatin	diabetic patients	secondary prevention	Low risk of bias	suggesting
TNT, 2005            NCT	atorvastatin high dose	atorvastatin	secondary prevention		Low risk of bias	conclusive
Vascular basis, 2005	atorvastatin high dose	lovastatin	secondary prevention		Exploratory	negative
PROVE IT - TIMI 22, 2004	atorvastatin	pravastatin	acute coronary syndrome	early initiation	Low risk of bias	suggesting
REVERSAL, 2004	atorvastatin high dose	pravastatin	secondary prevention		Exploratory	negative
PROVE-IT, 2004	atorvastatin high dose	pravastatin	diabetic	early initiation	Low risk of bias	suggesting
SAGE, 2007	atorvastatin high dose	pravastatin	secondary prevention		Exploratory	suggesting
IDEAL, 2005        NCT	atorvastatin high dose	simvastatin	secondary prevention		Risk of bias	suggesting
bezafibrate
SENDCAP, 1998	bezafibrate	placebo		type 2 diabetes	Exploratory	suggesting
LEADER, 2002	bezafibrate	placebo			Low risk of bias	negative
LEADER trial, 2000	bezafibrate	placebo	Peripheral Arterial Disease		Low risk of bias	-
BECAIT, 1996	bezafibrate	placebo	secondary prevention		Exploratory	suggesting
BIP, 2000	bezafibrate	placebo	secondary prevention		Low risk of bias	negative
cerivastatin
Laufs, 2004	cerivastatin	placebo	heart failure		Low risk of bias	-
cholestyramine
STARS (cholestyramine), 1992	cholestyramine	control			Low risk of bias	negative
LRC, 1984	cholestyramine	placebo			Low risk of bias	negative
NHLBI (Brensike), 1984    NCT	cholestyramine	placebo	diabetic		Exploratory	negative
clofibrate
WHO clofibrate, 1978	clofibrate	placebo			Low risk of bias	suggesting
Cullen, 1974	clofibrate	placebo			Low risk of bias	-
Harrold, 1969	clofibrate	placebo		type 2 diabetes	Low risk of bias	-
Hanefeld, 1991	clofibrate	placebo		type 2 diabetes	Low risk of bias	negative
Begg, 1971	clofibrate	placebo	secondary prevention		Exploratory	negative
Acheson, 1972	clofibrate	placebo	secondary prevention	cerebral vascular disease	Exploratory	-
VA Neurology Section, 1974	clofibrate	placebo			Low risk of bias	-
CDP Clofibrate, 1975	clofibrate	placebo			Low risk of bias	suggesting
Scottish, 1971	clofibrate	placebo			Low risk of bias	negative
Newcastle, 1971	clofibrate	placebo			Low risk of bias	suggesting
SCOR, 1990	colestipol+clofibrate	placebo	diabetic		Low risk of bias	negative
colestipol
UCS (Dorr), 1978	colestipol	placebo			Low risk of bias	negative
Ryan, 1974	colestipol	placebo			Low risk of bias	-
Gundersen, 1976	colestipol	placebo			Low risk of bias	-
Ruoff, 1978	colestipol	placebo			Low risk of bias	negative
Gross, 1973	colestipol	placebo			Low risk of bias	-
diet
Veterans Ad. (Dayton), 1969	diet	usual diet			Low risk of bias	suggesting
MRFIT, 1982	diet	usual diet			Risk of bias	-
Hjermann, 1981	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
Goteborg, 1986	diet	usual diet			Risk of bias	-
Rose, 1965	diet	usual diet			Exploratory	negative
Singh, 1992	diet	usual diet			Risk of bias	-
STARS (St Thomas, diet), 1992	diet	usual diet			Exploratory	negative
Los Angeles VA (Dayton), 1969	diet	usual diet			Low risk of bias	-
Ornish, 1990	diet	usual diet			Exploratory	negative
Kallio, 1979	diet	usual diet			Exploratory	-
MRC Soya, 1968	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 low fat, 1965	diet	usual diet			Risk of bias	negative
WHI low fat, 2005    NCT	diet	usual diet			Exploratory	negative
Göteborg (Wilhelmsen), 1986	diet	usual diet			Low risk of bias	negative
Black, 1994	diet	usual diet			Risk of bias	negative
Minnesota coronary survey (Frantz), 1975	diet	usual diet			Exploratory	negative
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	-
CDP estrogen 5, 1975	estrogen	placebo			Low risk of bias	-
CDP estrogen 2.5, 1975	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
etofibrate
Emmerich, 2009	etofibrate	placebo	diabetic	type 2 diabetes	Exploratory	-
ezetimibe
SHARP, 2010      NCT	ezetimibe+simvastatin	placebo			Low risk of bias	suggesting
IMPROVE-IT, 2014      NCT	ezetimibe	placebo (on top statins)		early initiation	Low risk of bias	conclusive
Enhance, 2008	ezetimibe	placebo (on top statins)			Low risk of bias	-
SANDS, 2008      NCT	aggressive treatment	standard teatment	diabetic	type 2 diabetes	Exploratory	negative
ARBITER-HALTS 6, 2010	ezetimibe	niacin			Exploratory	-
fenofibrate
FIELD, 2005	fenofibrate	placebo	diabetic patients		Low risk of bias	suggesting
DAIS, 2001	fenofibrate	placebo	diabetic	type 2 diabetes	Exploratory	negative
FIELD, 2005	fenofibrate	placebo	diabetic	type 2 diabetes	Low risk of bias	suggesting
ACCORD lipid, 2010    NCT	fenofibrate	placebo (on top simvastatine)	diabetic patients		Low risk of bias	negative
fluvastatin
LIPS (diabetic sub group), 2002	fluvastatin	placebo	diabetic patients	secondary prevention	Exploratory	suggesting
ALERT (diabetic sub group), 2003	fluvastatin	placebo	diabetic patients		Low risk of bias	-
FLARE (elderly subgroup), 1999	fluvastatin	placebo	elderly	elderly	Low risk of bias	negative
LIPS (elderly subgroup), 2002	fluvastatin	placebo	elderly	elderly	Low risk of bias	suggesting
LIPS (sub groups), 2002	fluvastatin	placebo	acute coronary syndrome	early initiation	Low risk of bias	negative
FLORIDA, 2002	fluvastatin	placebo	acute coronary syndrome	early initiation	Low risk of bias	negative
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
BCAPS, 2001	fluvastatin	placebo	primary prevention	cerebral vascular disease	Low risk of bias	negative
ALERT, 2003	fluvastatin	placebo	CKD	kidney diseases	Low risk of bias	suggesting
LIPS, 2002	fluvastatin	placebo	secondary prevention		Low risk of bias	suggesting
ALERT, 2003	fluvastatin	placebo			Low risk of bias	negative
HYRIM, 2005	fluvastatin	placebo	hypertensive	hypertensive patients	Exploratory	negative
gemfibrozil
Helsinki (HHS), 1987	gemfibrozil	placebo			Low risk of bias	suggesting
HHS (diabetic sub group), 1987	gemfibrozil	placebo	diabetic patients	primary prevention	Low risk of bias	-
VA-HIT (diabetic sub group), 1999	gemfibrozil	placebo	diabetic patients	secondary prevention	Low risk of bias	negative
VA-HIT, 1999      NCT	gemfibrozil	placebo			Low risk of bias	suggesting
HHS (Frick)(secondary prev subgroup), 1993	gemfibrozil	placebo			Exploratory	negative
LOCAT, 1997	gemfibrozil	placebo			Exploratory	negative
lovastatin
AFCAPS/TexCAPS, 1998	lovastatin	placebo	primary prevention		Low risk of bias	conclusive
AFCAPS/TexCAPS (diabetic sub group), 1998	lovastatin	placebo	diabetic patients	primary prevention	Low risk of bias	-
CRISP 20mg, 1994    NCT	lovastatin	placebo	diabetic		Exploratory	-
ACAPS, 1994    NCT	lovastatin	placebo	secondary prevention	cerebral vascular disease	Exploratory	suggesting
CCAIT, 1994	lovastatin	placebo	secondary prevention		Exploratory	negative
MARS, 1993      NCT	lovastatin	placebo	secondary prevention		Exploratory	negative
Excel, 1991	lovastatin	placebo			Exploratory	negative
Weintraub, 1994	lovastatin	placebo	secondary prevention		Low risk of bias	negative
CRISP 40mg, 1994    NCT	lovastatin	placebo	diabetic		Exploratory	-
AFCAPS (women subgroup) , 1998	Lovastatin	placebo	women		Exploratory	negative
Sahni, 1991	lovastatin	usual care	secondary prevention		Risk of bias	negative
CLAPT, 1999	lovastatin	usual care	secondary prevention		Exploratory	negative
niacin
VA drugs, 1968	niacin	control			Low risk of bias	negative
Carlson (Stockholm), 1977	clofibtate+niacin	placebo	secondary prevention		Risk of bias	suggesting
CLAS, 1987	colestipol-niacin	placebo	secondary prevention		Exploratory	negative
CLAS, 1987	colestipol-niacin	placebo	Peripheral Arterial Disease		Exploratory	-
CDP niacin, 1975	niacin	placebo			Low risk of bias	suggesting
AIM-HIGH, 2011      NCT	niacin	placebo (on top statin)			Low risk of bias	negative
HPS 2-Thrive      NCT	niacin	placebo (on top statin)			Low risk of bias	negative
Oxford Niaspan Study, 2009    NCT	niacin	placebo (on top statin)			Exploratory	-
ARBITER 2, 2009	niacin	placebo (on top statin)			Exploratory	negative
HATS, 2001	niacin	placebo (on top statin)			Low risk of bias	negative
ARBITER 6-HALTS (niacin vs ezetimibe), 2009        NCT	niacin	ezetimibe			Exploratory	suggesting
policosanol
Castano, 2001	policosanol	control	diabetic		Low risk of bias	negative
Más, 1999	policosanol	control			Exploratory	negative
Batista, 1996	policosanol	control			Low risk of bias	-
pravastatin
MEGA, 2006        NCT	pravastatin	control	primary prevention		Risk of bias	suggesting
FAST Fukuoka pravastatin, 2002	pravastatin	control	primary prevention		Exploratory	-
WOSCOPS, 1995	pravastatin	placebo	primary prevention		Low risk of bias	conclusive
PROSPER diabetic (sub group), 2002	pravastatin	placebo	diabetic patients	secondary prevention	Low risk of bias	negative
LIPID (diabetic sub group), 1998	pravastatin	placebo	diabetic patients	secondary prevention	Low risk of bias	negative
CARE (diabetic sub group), 1998	pravastatin	placebo	diabetic patients	secondary prevention	Exploratory	suggesting
WOSCOPS (diabetic sub group), 1996	pravastatin	placebo	diabetic patients	primary prevention	Low risk of bias	-
PROSPER, 2002	pravastatin	placebo	secondary prevention	elderly	Low risk of bias	conclusive
CARE (elderly subgroup), 1998	Pravastatin	placebo	elderly	elderly	Low risk of bias	suggesting
LIPID (elderly sub group), 2001	Pravastatin	placebo	elderly	elderly	Low risk of bias	suggesting
PLAC I (elderly sub group), 1995	Pravastatin	placebo	elderly	elderly	Low risk of bias	negative
REGRESS (elderly subgroup), 1995	Pravastatin	placebo	elderly	elderly	Low risk of bias	negative
REGRESS, 1995	pravastatin	placebo	secondary prevention		Exploratory	suggesting
PMSG, 1993	pravastatin	placebo	primary prevention		Exploratory	negative
LIPID, 1998	pravastatin	placebo	secondary prevention		Low risk of bias	conclusive
CARE, 1996	pravastatin	placebo	secondary prevention		Low risk of bias	conclusive
LAMIL, 1997	pravastatin	placebo	acute coronary syndrome	early initiation	Low risk of bias	negative
RECIFE, 1999	pravastatin	placebo	acute coronary syndrome	early initiation	Low risk of bias	negative
PAIS, 2001	pravastatin	placebo	acute coronary syndrome	early initiation	Low risk of bias	negative
PACT, 2004	pravastatin	placebo	acute coronary syndrome	early initiation	Low risk of bias	suggesting
CAIUS, 1996	pravastatin	placebo	primary prevention	cerebral vascular disease	Exploratory	negative
PREVEND IT, 2004	pravastatin	placebo	related disease	kidney diseases	Low risk of bias	negative
PLAC I, 1995	pravastatin	placebo	secondary prevention		Exploratory	suggesting
PLAC II, 1995	pravastatin	placebo	secondary prevention		Exploratory	negative
PACT, 2004	pravastatin	placebo	secondary prevention		Low risk of bias	negative
KAPS, 1995	pravastatin	placebo	primary prevention		Exploratory	negative
PHYLLIS, 2004	pravastatin	placebo	diabetic	cerebral vascular disease hypertensive patients	Exploratory	-
PROSPER (primary prevention subgroup), 2002	pravastatin	placebo	primary prevention	elderly	Exploratory	negative
ALLHAT (women subgroup) , 2002	Pravastatin	placebo	women		Exploratory	negative
MEGA (women subgroup) , 2006	Pravastatin	placebo	women		Exploratory	suggesting
GISSI P (diabetic sub group), 2000	pravastatin	usual care	diabetic patients	secondary prevention	Exploratory	-
ALLHAT-LLT (diabetic sub group), 2002	pravastatin	usual care	diabetic patients	secondary prevention	Exploratory	negative
ALLHAT, 2002      NCT	pravastatin	usual care	at risk hypertensive	hypertensive patients	Risk of bias	negative
L-CAD, 2000	pravastatin	usual care	acute coronary syndrome	early initiation	Exploratory	suggesting
PTT, 2002	pravastatin	usual care	acute coronary syndrome	early initiation	Exploratory	suggesting
GISSI Prevenzione, 2000	pravastatin	usual care	secondary prevention		Risk of bias	negative
KLIS, 2000	pravastatin	usual care	primary prevention		Risk of bias	-
PROVE IT TIMI 22 (diabetic sub group), 2006	pravastatin high dose	pravastatin	diabetic patients	secondary prevention	Low risk of bias	-
probucol
FATS Fukosawa (probucol), 2002	probucol	control	primary prevention		Exploratory	-
McCaughan, 1981	Probucol	placebo			Exploratory	-
Tardif, 1997	Probucol	placebo			Low risk of bias	negative
PQRST, 1994	probucol	placebo	Peripheral Arterial Disease		Exploratory	-
PQRST, 1994	probucol	placebo			Exploratory	-
rosuvastatin
JUPITER (elderly sub group), 2009	rosuvastatin	placebo	elderly	elderly	Low risk of bias	suggesting
JUPITER, 2008    NCT	rosuvastatin	placebo	primary prevention		Low risk of bias	conclusive
ASTRONOMER, 2010	rosuvastatin	placebo	aortic stenosis		Low risk of bias	-
METEOR, 2007      NCT	rosuvastatin	placebo	diabetic		Exploratory	negative
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
AURORA, 2009	rosuvastatin	placebo			Low risk of bias	negative
HOPE 3, 2016      NCT	rosuvastatin	placebo	primary prevention		Low risk of bias	conclusive
JUPITER (women subgroup) , 2008	Rosuvastatin	placebo	women		Exploratory	suggesting
simvastatin
Hong, 2005	simvastatin	control	heart failure		Risk of bias	negative
SEAS, 2008    NCT	ezetimibe+simvastatin	placebo	aortic stenosis		Low risk of bias	negative
HPS (diabetic sub group), 2002	simvastatin	placebo	diabetic patients		Low risk of bias	suggesting
4S (diabetic sub group), 1999	simvastatin	placebo	diabetic patients	secondary prevention	Low risk of bias	suggesting
HPS (diabetic primary prevention sub group), 2003	simvastatin	placebo	diabetic	type 2 diabetes	Exploratory	-
4S (elderly subgroup), 1997	simvastatin	placebo	elderly	elderly	Low risk of bias	suggesting
HPS (elderly subgroup), 2002	simvastatin	placebo	elderly	elderly	Low risk of bias	suggesting
HPS, 2002	simvastatin	placebo	secondary prevention		Low risk of bias	conclusive
4S, 1994	simvastatin	placebo	secondary prevention		Low risk of bias	conclusive
A to Z, 2004	simvastatin	placebo	acute coronary syndrome	early initiation		negative
CIS, 1997	simvastatin	placebo	secondary prevention		Exploratory	negative
Mondillo, 2003	simvastatin	placebo	Peripheral Arterial Disease		Exploratory	-
Aronow , 2003	simvastatin	placebo	Peripheral Arterial Disease		Exploratory	-
MAAS, 1994	simvastatin	placebo	secondary prevention		Exploratory	negative
Node, 2003	simvastatin	placebo	heart failure			negative
HPS (post troke sub group), 2004	simvastatin	placebo	post stroke	cerebral vascular disease	Low risk of bias	suggesting
HPS (women subgroup) , 2002	Simvastatin	placebo	women		Exploratory	suggesting
Landmesser, 2005	simvastatin	ezetimibe	heart failure			-
SEARCH, 2010    NCT	simvastatin high dose	simvastatin	secondary prevention		Low risk of bias	suggesting
thyroxine
CDP tyroxine, 1975	thyroxine	placebo			Low risk of bias	-
diet
not classified
NORDIET	diet	control				-
BARON	diet	control				-
HPT	diet	control				-
Kumanyika	diet	control				-
TAIM	diet	control				-
DISH	diet	control				-
Lyon	Mediterranean diet	control				suggesting
PREDIMED (olive oil), 2013	Mediterranean diet with EOVV	control			Risk of bias	suggesting
PREDIMED (nuts), 2013	Mediterranean diet with nuts	control				suggesting
DART (Burr), 1989	diet	usual diet	secondary prevention		Exploratory	negative
Finnish Mental Hospital (Turpeinen), 1979	diet	usual diet	primary prevention		Exploratory	negative
diet
Veterans Ad. (Dayton), 1969	diet	usual diet			Low risk of bias	suggesting
MRC Soya, 1968	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
Rose, 1965	diet	usual diet			Exploratory	negative
MRC low fat, 1965	diet	usual diet			Risk of bias	negative
WHI low fat, 2005    NCT	diet	usual diet			Exploratory	negative
Singh, 1992	diet	usual diet			Risk of bias	-
STARS (St Thomas, diet), 1992	diet	usual diet			Exploratory	negative
Los Angeles VA (Dayton), 1969	diet	usual diet			Low risk of bias	-
Ornish, 1990	diet	usual diet			Exploratory	negative
Kallio, 1979	diet	usual diet			Exploratory	-
MRFIT, 1982	diet	usual diet			Risk of bias	-
Hjermann, 1981	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
Black, 1994	diet	usual diet			Risk of bias	negative
Goteborg, 1986	diet	usual diet			Risk of bias	-
Minnesota coronary survey (Frantz), 1975	diet	usual diet			Exploratory	negative
Tuttle, 2008	low fat diet	mediterranean-style diet			Risk of bias	-
dietary salt reduction
not classified
Kumanyika, 1993	sodium reduction	control				-
DISH, 1985	sodium reduction	control				-
Chang, 2006	sodium reduction	control			Risk of bias	negative
HPT, 1990	sodium reduction	control			Risk of bias	negative
Morgan, 1978	sodium reduction	control			Exploratory	negative
Paterna, 2008	sodium reduction	control			Risk of bias	-
TOHP I, 1992	sodium reduction	control			Risk of bias	suggesting
TOHP II, 1997	sodium reduction	control			Risk of bias	negative
TONE, 1998	sodium reduction	control			Risk of bias	negative
Alli, 1992	sodium reduction	control			Exploratory	-
Arroll, 1995	sodium reduction	control			Exploratory	-
Costa, 1981	sodium reduction	control			Exploratory	-
Morgan, 1987	sodium reduction	control			Exploratory	-
Silman, 1993	sodium reduction	control			Exploratory	-
Thaler, 1982	sodium reduction	control			Exploratory	-
direct factor Xa inhibitors
rivaroxaban
COMPASS (rivaroxaban alone), 2017    NCT	rivaroxaban	aspirin	secondary prevention			-
COMPASS (rivaroxaban + aspirin), 2017      NCT	rivaroxaban + aspirin	aspirin	secondary prevention		Low risk of bias	-
direct oral anticoagulant (DAO)
rivaroxaban
COMPASS (rivaroxaban alone), 2017    NCT	rivaroxaban	aspirin	secondary prevention			-
COMPASS (rivaroxaban + aspirin), 2017      NCT	rivaroxaban + aspirin	aspirin	secondary prevention		Low risk of bias	-
HDL increasing drugs
not classified
REVEAL HPS-3 TIMI-55, 2017    NCT	anacetrapib	placebo			Low risk of bias	remark
dal-VESSEL, 2011	dalcetrapib	placebo			Exploratory	-
dal-OUTCOMES, 2012      NCT	dalcetrapib	placebo			Low risk of bias	negative
ACCELERATE, 2017      NCT	evacetrapib	placebo			Low risk of bias	suggesting
anacetrapib
DEFINE, 2010    NCT	anacetrapib	placebo			Exploratory	negative
REALIZE, 2015      NCT	anacetrapib	placebo			Low risk of bias	negative
bezafibrate
BECAIT, 1996	bezafibrate	placebo	secondary prevention		Exploratory	suggesting
BIP, 2000	bezafibrate	placebo	secondary prevention		Low risk of bias	negative
SENDCAP, 1998	bezafibrate	placebo		type 2 diabetes	Exploratory	suggesting
LEADER, 2002	bezafibrate	placebo			Low risk of bias	negative
clofibrate
WHO clofibrate, 1978	clofibrate	placebo			Low risk of bias	suggesting
CDP Clofibrate, 1975	clofibrate	placebo			Low risk of bias	suggesting
Scottish, 1971	clofibrate	placebo			Low risk of bias	negative
Newcastle, 1971	clofibrate	placebo			Low risk of bias	suggesting
Harrold, 1969	clofibrate	placebo		type 2 diabetes	Low risk of bias	-
Begg, 1971	clofibrate	placebo	secondary prevention		Exploratory	negative
Acheson, 1972	clofibrate	placebo	secondary prevention	cerebral vascular disease	Exploratory	-
VA Neurology Section, 1974	clofibrate	placebo			Low risk of bias	-
Cullen, 1974	clofibrate	placebo			Low risk of bias	-
Hanefeld, 1991	clofibrate	placebo		type 2 diabetes	Low risk of bias	negative
etofibrate
Emmerich, 2009	etofibrate	placebo	diabetic	type 2 diabetes	Exploratory	-
fenofibrate
FIELD, 2005	fenofibrate	placebo	diabetic	type 2 diabetes	Low risk of bias	suggesting
DAIS, 2001	fenofibrate	placebo	diabetic	type 2 diabetes	Exploratory	negative
ACCORD lipid, 2010    NCT	fenofibrate	placebo (on top simvastatine)	diabetic patients		Low risk of bias	negative
gemfibrozil
VA-HIT, 1999      NCT	gemfibrozil	placebo			Low risk of bias	suggesting
Helsinki (HHS), 1987	gemfibrozil	placebo			Low risk of bias	suggesting
HHS (Frick)(secondary prev subgroup), 1993	gemfibrozil	placebo			Exploratory	negative
LOCAT, 1997	gemfibrozil	placebo			Exploratory	negative
niacin
VA drugs, 1968	niacin	control			Low risk of bias	negative
CDP niacin, 1975	niacin	placebo			Low risk of bias	suggesting
AIM-HIGH, 2011      NCT	niacin	placebo (on top statin)			Low risk of bias	negative
HPS 2-Thrive      NCT	niacin	placebo (on top statin)			Low risk of bias	negative
Oxford Niaspan Study, 2009    NCT	niacin	placebo (on top statin)			Exploratory	-
ARBITER 2, 2009	niacin	placebo (on top statin)			Exploratory	negative
HATS, 2001	niacin	placebo (on top statin)			Low risk of bias	negative
ARBITER 6-HALTS (niacin vs ezetimibe), 2009        NCT	niacin	ezetimibe			Exploratory	suggesting
torcetrapib
RADIANCE 1, 2007      NCT	torcetrapib	placebo			Exploratory	negative
ILLUMINATE, 2007      NCT	torcetrapib	placebo			Low risk of bias	negative
RADIANCE 2, 2007	torcetrapib	placebo			Low risk of bias	-
ILLUSTRATE, 2007      NCT	torcetrapib	placebo			Exploratory	negative
hormonal replacement therapy
not classified
PEPI, 1995    NCT	hormonal replacement therapy	placebo			Low risk of bias	-
estrogen
WAVE, 2002      NCT	combined estrogen and progestogen	placebo			Low risk of bias	negative
EAGAR, 2006      NCT	combined estrogen and progestogen	placebo			Low risk of bias	negative
HERS, 1998          NCT	combined estrogen and progestogen	placebo			Low risk of bias	negative
EVTET, 2000	combined estrogen and progestogen	placebo			Low risk of bias	negative
Hall, 1998	combined estrogen and progestogen	placebo			Low risk of bias	negative
WHI, 2002	combined estrogen and progestogen	placebo			Low risk of bias	negative
WHISP, 2006	combined estrogen and progestogen	placebo			Low risk of bias	negative
WISDOM, 2007	combined estrogen and progestogen	placebo			Low risk of bias	negative
ERA (estrogen plus medroxyprogesterone), 2000      NCT	combined estrogen and progestogen	placebo			Low risk of bias	negative
WELL-HART (estrogen-progestin), 2003      NCT	combined estrogen and progestogen	placebo			Low risk of bias	negative
Schulman (NHLBI) (estrogen-progestogen), 2002      NCT	combined estrogen and progestogen	placebo			Low risk of bias	-
ERA (estrogen alone ), 2000        NCT	estrogen	placebo			Low risk of bias	negative
WELL-HART (estrogen alone), 2003      NCT	estrogen	placebo			Low risk of bias	negative
Schulman (NHLBI) (estrogen alone), 2002      NCT	estrogen	placebo			Low risk of bias	-
EPAT, 2001	estrogen	placebo			Low risk of bias	negative
ESPRIT, 2002	estrogen	placebo			Low risk of bias	negative
WEST, 2001	estrogen	placebo			Low risk of bias	negative
lifestyle intervention
not classified
NORDIET	diet	control				-
BARON	diet	control				-
HPT	diet	control				-
Kumanyika	diet	control				-
TAIM	diet	control				-
DISH	diet	control				-
Lyon	Mediterranean diet	control				suggesting
PREDIMED (olive oil), 2013	Mediterranean diet with EOVV	control			Risk of bias	suggesting
PREDIMED (nuts), 2013	Mediterranean diet with nuts	control				suggesting
CELL, 1995	Multiple risk factor interventions	control			Risk of bias	negative
Family Heart, 1994	Multiple risk factor interventions	control			Low risk of bias	suggesting
Göteborg Study, 1986	Multiple risk factor interventions	control			Risk of bias	negative
HDFP, 1979    NCT	Multiple risk factor interventions	control			Risk of bias	suggesting
Johns Hopkins, 1983	Multiple risk factor interventions	control			Risk of bias	suggesting
MRFIT, 1982    NCT	Multiple risk factor interventions	control			Risk of bias	suggesting
Meland, 1997	Multiple risk factor interventions	control			Exploratory	negative
OXCHECK, 1994	Multiple risk factor interventions	control			Risk of bias	negative
Oslo, 1981	Multiple risk factor interventions	control			Risk of bias	negative
WHO Factories, 1982	Multiple risk factor interventions	control			Risk of bias	suggesting
Helsinki Businessmen Study, 1985	Multiple risk factor interventions	control			Risk of bias	negative
DART (Burr), 1989	diet	usual diet	secondary prevention		Exploratory	negative
Finnish Mental Hospital (Turpeinen), 1979	diet	usual diet	primary prevention		Exploratory	negative
diet
Veterans Ad. (Dayton), 1969	diet	usual diet			Low risk of bias	suggesting
MRC Soya, 1968	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
Rose, 1965	diet	usual diet			Exploratory	negative
MRC low fat, 1965	diet	usual diet			Risk of bias	negative
WHI low fat, 2005    NCT	diet	usual diet			Exploratory	negative
Singh, 1992	diet	usual diet			Risk of bias	-
STARS (St Thomas, diet), 1992	diet	usual diet			Exploratory	negative
Los Angeles VA (Dayton), 1969	diet	usual diet			Low risk of bias	-
Ornish, 1990	diet	usual diet			Exploratory	negative
Kallio, 1979	diet	usual diet			Exploratory	-
MRFIT, 1982	diet	usual diet			Risk of bias	-
Hjermann, 1981	diet	usual diet			Risk of bias	-
Finnish Mental Hospital (Miettinen), 1985	diet	usual diet	primary prevention		Exploratory	-
Göteborg (Wilhelmsen), 1986	diet	usual diet			Low risk of bias	negative
Black, 1994	diet	usual diet			Risk of bias	negative
Goteborg, 1986	diet	usual diet			Risk of bias	-
Minnesota coronary survey (Frantz), 1975	diet	usual diet			Exploratory	negative
Tuttle, 2008	low fat diet	mediterranean-style diet			Risk of bias	-
niacin
not classified
AFREGS, 2005	strategy to increase HDL cholesterol	placebo			Low risk of bias	negative
niacin
VA drugs, 1968	niacin	control			Low risk of bias	negative
UCSF SCOR, 1990	niacin+colestipol	control			Exploratory	negative
Carlson (Stockholm), 1977	clofibtate+niacin	placebo	secondary prevention		Risk of bias	suggesting
CLAS, 1987	colestipol-niacin	placebo	secondary prevention		Exploratory	negative
CDP niacin, 1975	niacin	placebo			Low risk of bias	suggesting
FATS, 1990	niacin+colestipol	placebo			Low risk of bias	suggesting
AIM-HIGH, 2011      NCT	niacin	placebo (on top statin)			Low risk of bias	negative
HPS 2-Thrive      NCT	niacin	placebo (on top statin)			Low risk of bias	negative
Oxford Niaspan Study, 2009    NCT	niacin	placebo (on top statin)			Exploratory	-
ARBITER 2, 2009	niacin	placebo (on top statin)			Exploratory	negative
HATS, 2001	niacin	placebo (on top statin)			Low risk of bias	negative
ARBITER 6-HALTS (niacin vs ezetimibe), 2009        NCT	niacin	ezetimibe			Exploratory	suggesting
Guyton, 2008	niacin+ezetimibe	simvastatin+ezetimibe			Low risk of bias	negative
omega-3 fatty acids
not classified
Bellamy, 1992	MaxEPA	control			Exploratory	-
Dehmer, 1998	MaxEPA	control			Exploratory	negative
Kaul, 1992	MaxEPA	control			Exploratory	negative
OMEGA, 2009      NCT	omega-3 Fatty acids	control			Risk of bias	negative
Milner, 1989	Promega	control				-
Natvig, 1968	alpha-linolenic acid	placebo			Low risk of bias	negative
ALPHA OMEGA (ALA), 2010    NCT	alpha-linolenic acid	placebo			Low risk of bias	negative
Veale, 1994	Efamol marine	placebo			Low risk of bias	-
Maresta, 2002	Esapent	placebo			Low risk of bias	negative
Sirtori, 1998	Esapent	placebo			Low risk of bias	-
Rossing, 1996	Eskisol	placebo			Low risk of bias	negative
Hawthorne, 1992	HiEPA	placebo			Low risk of bias	-
Bairati, 1992	MaxEPA	placebo			Low risk of bias	-
Greenfield, 1993	MaxEPA	placebo			Low risk of bias	-
Lau, 1993	MaxEPA	placebo			Low risk of bias	-
Lau, 1995	MaxEPA	placebo			Low risk of bias	-
Nye, 1990	MaxEPA	placebo			Low risk of bias	-
Singh, 1997	MaxEPA	placebo			Low risk of bias	suggesting
Skoldstam, 1992	MaxEPA	placebo			Low risk of bias	-
Thien, 1993	MaxEPA	placebo			Low risk of bias	-
GISSI HF fatty acid, 2008    NCT	omega-3 fatty acids	placebo	heart failure		Low risk of bias	negative
ALPHA OMEGA (EPA DHA), 2010    NCT	omega-3 Fatty acids	placebo			Low risk of bias	negative
Risk and Prevention Study, 2013        NCT	omega-3 Fatty acids	placebo			Low risk of bias	negative
Bonnema, 1995	Pikasol	placebo			Low risk of bias	-
Connor, 1993	Promega	placebo			Low risk of bias	-
Sacks (HARP), 1995	Promega	placebo			Low risk of bias	negative
Belluzzi, 1996	PurEPA	placebo			Low risk of bias	-
Reis, 1991	Super EPA	placebo			Low risk of bias	-
diet
Burr (DART), 1989	diet	control				suggesting
Burr (DART 2), 2003	diet	control				negative
Mate-Jimenez, 1991	diet	control			Exploratory	-
fish oil
Bemelmans, 2002	fish oil	control			Low risk of bias	negative
Brox, 2001	fish oil	control			Exploratory	negative
Franzen, 1993	fish oil	control			Low risk of bias	-
Katan, 1997	fish oil	control			Exploratory	-
Malaguarnera, 1999	fish oil	control			Exploratory	negative
Shimizu, 1995	fish oil	control			Exploratory	-
Terano, 1999	fish oil	control			Exploratory	negative
Almallah, 1998	fish oil	placebo			Exploratory	-
Borchgrevink, 1966	fish oil	placebo			Low risk of bias	negative
Dry, 1991	fish oil	placebo			Low risk of bias	-
Geusens, 1994	fish oil	placebo			Low risk of bias	-
Leaf, 1994	fish oil	placebo			Low risk of bias	negative
Loeschke, 1996	fish oil	placebo			Low risk of bias	negative
Lorenz-Meyer, 1996	fish oil	placebo			Low risk of bias	-
Sacks (TOHP 1), 1994    NCT	fish oil	placebo			Low risk of bias	-
von Schacky, 1999	fish oil	placebo			Low risk of bias	negative
omacor
Eritsland, 1996	Omacor	control				negative
GISSI-P, 1999	Omacor	control			Risk of bias	suggesting
Johansen, 1999	Omacor	placebo			Low risk of bias	negative
Nilsen, 2001	Omacor	placebo			Low risk of bias	negative
on top statins
alirocumab
ODYSSEY OUTCOMES, 2018      NCT	alirocumab	placebo (on top statins)			Low risk of bias	conclusive
evolocumab
FOURIER, 2017      NCT	evolocumab	placebo (on top statins)			Low risk of bias	conclusive
ezetimibe
IMPROVE-IT, 2014      NCT	ezetimibe	placebo (on top statins)		early initiation	Low risk of bias	conclusive
PCSK9 Inhibitors
alirocumab
ODYSSEY OPTIONS I	alirocumab	ezetimibe (on top statin)				negative
ODYSSEY OPTIONS II	alirocumab	ezetimibe (on top statin)				negative
ODYSSEY MONO      NCT	alirocumab	ezetimibe alone			Low risk of bias	negative
ODYSSEY Long-Term, 2015      NCT	alirocumab	placebo (on top statins)			Exploratory	suggesting
ODYSSEY Alternative      NCT	alirocumab	placebo (on top statins)			Low risk of bias	negative
ODYSSEY OUTCOMES, 2018      NCT	alirocumab	placebo (on top statins)			Low risk of bias	conclusive
ODYSSEY FH 1      NCT	alirocumab	placebo (on top statins)			Low risk of bias	-
ODYSSEY FH 2      NCT	alirocumab	placebo (on top statins)			Low risk of bias	-
ODYSSEY HIGH FH      NCT	alirocumab	placebo (on top statins)				negative
ODYSSEY COMBO        NCT	alirocumab	placebo (on top statins)			Low risk of bias	negative
ODYSSEY COMBO II        NCT	alirocumab	placebo (on top statins)			Low risk of bias	negative
evolocumab
MENDEl 2    NCT	evolocumab					-
Mendel 1, 2012      NCT	evolocumab					-
YUKAWA-1, 2014	evolocumab					-
GAUSS 2    NCT	evolocumab	ezetimibe alone				negative
GAUSS 1, 2012    NCT	evolocumab	placebo				negative
FOURIER, 2017      NCT	evolocumab	placebo (on top statins)			Low risk of bias	conclusive
DESCARTES, 2014    NCT	evolocumab	placebo (on top statins)				negative
LAPLACE-TIMI 57    NCT	evolocumab	placebo (on top statins)				-
RUTHERFORD-1    NCT	evolocumab	placebo (on top statins)				negative
LAPLACE 2, 2014    NCT	evolocumab	placebo (on top statins)				negative
RUTHERFORD-2, 2015    NCT	evolocumab	placebo (on top statins)				negative
plasma homocysteine lowering intervention
not classified
NORVIT (vit B6) (Bonaa), 2006    NCT	vit B6	control			Low risk of bias	negative
WENBIT (vit B6), 2008    NCT	vit B6	placebo			Low risk of bias	negative
folic acid
FOLARDA (Liem), 2004	folic acid	control			Exploratory	negative
GOES (Liem), 2003	folic acid	control			Risk of bias	negative
NORVIT (folic acid + B12) (Bonaa), 2006    NCT	folic acid, B12	control			Low risk of bias	negative
NORVIT (folic acid, B12 and vit B6) (Bonaa), 2006    NCT	folic acid, vit B12 and vit B6	control			Low risk of bias	negative
CHAOS-2, 2002	folic acid	placebo			Low risk of bias	negative
CSPPT, 2015      NCT	folic acid	placebo			Low risk of bias	suggesting
SEARCH, 2007      NCT	folic acid, B12	placebo			Low risk of bias	negative
WENBIT (folic ac,B12), 2008    NCT	folic acid, B12	placebo			Low risk of bias	negative
WAFACS, 2008    NCT	folic acid, vit B12 and vit B6	placebo			Low risk of bias	negative
HOPE-2 (Lonn), 2006        NCT	folic acid, vit B12 and vit B6	placebo			Low risk of bias	suggesting
VITATOPS, 2010    NCT	folic acid, vit B12 and vit B6	placebo			Low risk of bias	suggesting
SU.FOL.OM3	folic acid, vit B12 and vit B6	placebo			Low risk of bias	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
polypill
not classified
TIPS, 2009        NCT	polypill	error			Low risk of bias	-
statins
not classified
DART (Burr), 1989	diet	usual diet	secondary prevention		Exploratory	negative
atorvastatin
Mohler, 2003	atorvastatin	placebo	secondary prevention		Low risk of bias	-
ASPEN, 2006	atorvastatin	placebo	diabetic	type 2 diabetes	Low risk of bias	negative
CARDS, 2004      NCT	atorvastatin	placebo	diabetic	type 2 diabetes	Low risk of bias	conclusive
ASCOT, 2003	atorvastatin	placebo	at risk hypertensive	hypertensive patients	Low risk of bias	conclusive
GREACE, 2002	atorvastatin	usual care	secondary prevention		Risk of bias	suggesting
AVERT, 1999	atorvastatin high dose	angioplasty	secondary prevention		Risk of bias	negative
TNT, 2005            NCT	atorvastatin high dose	atorvastatin	secondary prevention		Low risk of bias	conclusive
Vascular basis, 2005	atorvastatin high dose	lovastatin	secondary prevention		Exploratory	negative
REVERSAL, 2004	atorvastatin high dose	pravastatin	secondary prevention		Exploratory	negative
SAGE, 2007	atorvastatin high dose	pravastatin	secondary prevention		Exploratory	suggesting
IDEAL, 2005        NCT	atorvastatin high dose	simvastatin	secondary prevention		Risk of bias	suggesting
fluvastatin
BCAPS, 2001	fluvastatin	placebo	primary prevention	cerebral vascular disease	Low risk of bias	negative
LIPS, 2002	fluvastatin	placebo	secondary prevention		Low risk of bias	suggesting
HYRIM, 2005	fluvastatin	placebo	hypertensive	hypertensive patients	Exploratory	negative
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
lovastatin
Weintraub, 1994	lovastatin	placebo	secondary prevention		Low risk of bias	negative
AFCAPS/TexCAPS, 1998	lovastatin	placebo	primary prevention		Low risk of bias	conclusive
CCAIT, 1994	lovastatin	placebo	secondary prevention		Exploratory	negative
ACAPS, 1994    NCT	lovastatin	placebo	secondary prevention	cerebral vascular disease	Exploratory	suggesting
MARS, 1993      NCT	lovastatin	placebo	secondary prevention		Exploratory	negative
CRISP 20mg, 1994    NCT	lovastatin	placebo	diabetic		Exploratory	-
CRISP 40mg, 1994    NCT	lovastatin	placebo	diabetic		Exploratory	-
Sahni, 1991	lovastatin	usual care	secondary prevention		Risk of bias	negative
CLAPT, 1999	lovastatin	usual care	secondary prevention		Exploratory	negative
pravastatin
FAST Fukuoka pravastatin, 2002	pravastatin	control	primary prevention		Exploratory	-
MEGA, 2006        NCT	pravastatin	control	primary prevention		Risk of bias	suggesting
REGRESS, 1995	pravastatin	placebo	secondary prevention		Exploratory	suggesting
PROSPER, 2002	pravastatin	placebo	secondary prevention	elderly	Low risk of bias	conclusive
LIPID, 1998	pravastatin	placebo	secondary prevention		Low risk of bias	conclusive
CAIUS, 1996	pravastatin	placebo	primary prevention	cerebral vascular disease	Exploratory	negative
PROSPER (primary prevention subgroup), 2002	pravastatin	placebo	primary prevention	elderly	Exploratory	negative
PMSG, 1993	pravastatin	placebo	primary prevention		Exploratory	negative
WOSCOPS, 1995	pravastatin	placebo	primary prevention		Low risk of bias	conclusive
CARE, 1996	pravastatin	placebo	secondary prevention		Low risk of bias	conclusive
PACT, 2004	pravastatin	placebo	secondary prevention		Low risk of bias	negative
PHYLLIS, 2004	pravastatin	placebo	diabetic	cerebral vascular disease hypertensive patients	Exploratory	-
PLAC II, 1995	pravastatin	placebo	secondary prevention		Exploratory	negative
PLAC I, 1995	pravastatin	placebo	secondary prevention		Exploratory	suggesting
KLIS, 2000	pravastatin	usual care	primary prevention		Risk of bias	-
ALLHAT, 2002      NCT	pravastatin	usual care	at risk hypertensive	hypertensive patients	Risk of bias	negative
GISSI Prevenzione, 2000	pravastatin	usual care	secondary prevention		Risk of bias	negative
rosuvastatin
HOPE 3, 2016      NCT	rosuvastatin	placebo	primary prevention		Low risk of bias	conclusive
METEOR, 2007      NCT	rosuvastatin	placebo	diabetic		Exploratory	negative
JUPITER, 2008    NCT	rosuvastatin	placebo	primary prevention		Low risk of bias	conclusive
simvastatin
CIS, 1997	simvastatin	placebo	secondary prevention		Exploratory	negative
HPS, 2002	simvastatin	placebo	secondary prevention		Low risk of bias	conclusive
MAAS, 1994	simvastatin	placebo	secondary prevention		Exploratory	negative
HPS (diabetic primary prevention sub group), 2003	simvastatin	placebo	diabetic	type 2 diabetes	Exploratory	-
4S, 1994	simvastatin	placebo	secondary prevention		Low risk of bias	conclusive
SEARCH, 2010    NCT	simvastatin high dose	simvastatin	secondary prevention		Low risk of bias	suggesting
weight-loss drugs
not classified
RIO-North America 5mg, 2006						-
RIO-North America (20mg vs 5mg), 2006						-
RIO-diabetes, 2006      NCT					Low risk of bias	suggesting
STRADIVARIUS, 2008      NCT	rimonabant	placebo			Low risk of bias	-
rimonabant
CRESCENDO, 2010      NCT	rimonabant	placebo			Low risk of bias	negative
RIO europe 20mg, 2005	rimonabant 20mg	placebo			Low risk of bias	suggesting
Rio-lipid 20 mg, 2005	rimonabant 20mg	placebo			Low risk of bias	suggesting
RIO-North America 20 mg, 2006      NCT	rimonabant 20mg	placebo			Low risk of bias	suggesting
RIO europe 5mg, 2005	rimonabant 5mg	placebo			Low risk of bias	-
RIO europe (20 vs 5 mg), 2005	rimonabant 20mg	rimonabant 5mg				-