acute coronary syndrome

systematic review meta-analysis network meta-analysis

Select myocardial revascularizationcholesterol lowering interventionanticoagulantantiplatelets drugantithromboticsdirect factor Xa inhibitorsdirect oral anticoagulant (DAO)heparin (UFH or LMWH)New P2Y12 Inhibitorsanti-anginal drugscalcium channel blockersfibrinolysisnitratesoxygen therapy ACS (excluding AMI)All ACS (including AMI)All type of patientuncoded clinical condition ***elderly patientspatients with scheduled percutaneous coronary interventionunstable angina       antianginal drugsbivalirudincalcium-channel blockerscooling-off strategydirect thrombin inhibitorearly invasive strategyezetimibefibrinolyticlong term LMWHnitratesoral anticoagulantoral direct thrombin inhibitororal factor Xa inhibitoroxygen therapyP2Y12 receptor antagonistPAR-1 inhibitorplatelet aggregation inhibitorsreversible ADP receptor antagonistselective PAR-1 thrombin receptor antagonistshort term LMWHshort term UFHstatinssurgerysynthetic oligosaccharidethienopyridine atorvastatinfluvastatinpravastatinsimvastatinezetimibediltiazemnifedipineanistreplaseapixabanargatrobanaspirinatopaxarbivalirudincangrelorclopidogrelcoumadindabigatrandalteparindipyridamolEfegatranelinogrelenoxaparinfondaparinuxhirudininogatrannadroparinnitroglycerinotamixabanprasugrelranolazinerivaroxabansulfinpyrazonet-paticagrelorticlopidinetrapidiltriflusalUFHvorapaxarwarfarinximelagatran vs controlvs placebovs placebo and controlvs placebo or controlvs antiplatelet drugsvs aspirinvs clopidogrelvs eptifibatide + heparinvs heparinvs heparin+aGP2b3avs LMWHvs statinvs UFH       early initiation

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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	Major bleeding (169)All cause death (127)cardiovascular events (125)myocardial infarction (fatal and non fatal) (106)Non fatal MI (81)Vascular death (61)Revascularization (49)myocardial infarction or death (46)Non fatal stroke (44)stroke (fatal and non fatal) (42)all cause death, non-fatal MI, thrombo-embolic stroke (38)Non vascular death (37)Cardiovascular death (36)recurrent angina (32)major or clinically relevant non-major bleeding (31)intracranial hemorrhage (27)fatal bleeding (24)Extracranial hemorrhage (24)Bleeding (23)Minor bleeding (22)Fatal bleeding (15)any bleedings (15)non cardiovascular death (15)In-hospital death (14)Deaths or MI (13)cardiac event (fatal and non fatal ) (13)cardiac death (12)Fatal MI (12)In-hospital death (12)all cause death, MI, stroke (12)In hospital non fatal MI (11)In hospital death or MI (11)cardiovascular events at 1 month (10)cardiovascular events at 4 months (10)rehospitalization (10)myocardial infarction at 30 days (10)major or minor bleeding (10)death at 30 days (10)stent thrombosis (9)ischemic stroke (9)major bleeding TIMI (8)death, MI, unplanned revascularization (8)CCS class III-IV angina (7)death, myocardial infarction, or recurrent at 30 days (6)refractory ischemia (6)ischemic events + bleeding (4)Major or minor TIMI bleeding (4)Stent thrombosis (any, end of follow up) (4)Urgent target-vessel revascularization (4)death, myocardial infarction, or recurrent at 14 days (4)long term MI (3)long term cardiovascular death (3)long term all cause death, MI (3)Long term death (3)long term cardiovascular events (3)Repeat intervention (2)Drop in platelet count of 50% (2)no angina (at 6 weeks) (2)CABG (2)1 year composite ischemia (2)major bleeding not related to CABG (2)1 year MI (2)1 year unplanned revascularization for ischemia (2)1 year death from any cause (2)TIMI minor bleeding (2)in hospital death (patient with acute MI) (2)MACE (2)Death or stroke or myocardial infarction (1)Positive 6-wk ETT (1)Coronary event (1)Adverse events (1)Coronary death (1)PTCA (1)Death, MI, stroke, refractory ischemia (1)complication of AMI (1)dysrrhythmias (1)Recurrent ischemia (1) Options Numeric bar chart forest plot medians
Trial	Studied trt	Control trt	patients	tags	ROB	Trial result	Major bleeding	All cause death
anti-anginal drugs
ranolazine
MERLIN TIMI 36, 2007      NCT	ranolazine	placebo			Low risk of bias	suggesting
anticoagulant
apixaban
APPRAISE-1 (10mg od), 2009      NCT	apixaban	placebo			Low risk of bias	negative
APPRAISE-1 (2.5 mg bid), 2009      NCT	apixaban	placebo			Low risk of bias	negative
APPRAISE 2, 2011      NCT	apixaban	placebo			Low risk of bias	negative
coumadin
ASPECT-2 (coumadin+asp vs asp), 2002	coumadin	control (on top of aspirin)				suggesting
ASPECT-2 (coumadin vs aspirin), 2002	coumadin	aspirin				suggesting
dabigatran
REDEEM, 2009    NCT	dabigatran	placebo			Low risk of bias	negative
otamixaban
SEPIA-ACS1 TIMI 42, 2009    NCT	otamixaban	unfractionated heparin			Low risk of bias	suggesting
rivaroxaban
ATLAS ACS 2 - TIMI 51 (2.5mg), 2011      NCT	rivaroxaban 2.5mg	placebo			Low risk of bias	suggesting
ATLAS ACS-TIMI 46 (2.5mg), 2009      NCT	rivaroxaban 2.5mg	placebo			Low risk of bias	negative
ATLAS ACS 2 - TIMI 51 (5mg), 2011      NCT	rivaroxaban 5mg	placebo				suggesting
ATLAS ACS-TIMI 46 (5mg), 2009      NCT	rivaroxaban 5mg	placebo			Low risk of bias	negative
warfarin
ATACS (pilot study) (warfarin vs control), 1990	warfarin	control (on top of aspirin)				negative
ATACS, 1994	warfarin	control (on top of aspirin)				negative
CARS, 1997	warfarin	control (on top of aspirin)				negative
OASIS Pilot (phase 1), 1998	warfarin	control (on top of aspirin)				negative
OASIS Pilot (phase 2), 1998	warfarin	control (on top of aspirin)				negative
OASIS-2 Warfarin Substudy, 2001	warfarin	control (on top of aspirin)				negative
APRICOT-2, 2002	warfarin	control (on top of aspirin)				negative
CHAMP, 2002	warfarin	control (on top of aspirin)				negative
WARIS, 2002	warfarin	control (on top of aspirin)				suggesting
LoWASA, 2004	warfarin	control (on top of aspirin)				negative
Zibaeenezhad, 2004	warfarin	control (on top of aspirin)				negative
Williams, 1997	warfarin	placebo (on top of aspirin)			Low risk of bias	negative
Huyhn, 2001	warfarin	placebo (on top of aspirin)			Low risk of bias	negative
ATACS (pilot study) warfarin vs aspirin, 1990	warfarin	aspirin				negative
ximelagatran
ESTEEM, 2003	ximelagatran	placebo			Exploratory	-
antiplatelets drug
not classified
Jones, 1987	dazoxiben	control				negative
GRAND, 1987	GR3219B	control				negative
Gent-AMI, 1968	misc.	control				negative
Johannessen, 1989	misc.	control				negative
French, 1993	flurbiprofen	placebo			Low risk of bias	suggesting
CURRENT - OASIS 7 (ASA), 2010    NCT	ASA high dose	ASA low dose			Risk of bias	suggesting
aspirin
ATACS-pilot, 1990	aspirin	control				negative
Huddinge, 1988	aspirin	control				negative
Frankfurt, 1976	aspirin	control				negative
VA-pilot	aspirin	placebo				negative
VA-main, 1983	aspirin	placebo			Low risk of bias	suggesting
RISC, 1990	aspirin	placebo			Low risk of bias	suggesting
ALDUSA-pilot	aspirin	placebo				negative
Théroux, 1988	aspirin	placebo			Low risk of bias	suggesting
Canadian (Aspirin vs PBO), 1985	aspirin	placebo			Low risk of bias	-
Dutch-aspirin, 1990	aspirin	placebo			Low risk of bias	negative
ISIS-pilot, 1987	aspirin	placebo			Low risk of bias	negative
ISIS-2, 1988	aspirin	placebo			Low risk of bias	suggesting
APRICOT, 1993	aspirin	placebo			Low risk of bias	suggesting
Canadian (Aspirin + sulfinpyrazone), 1985	aspirin + sulfinpyrazone	placebo			Low risk of bias	negative
atopaxar
J-LANCELOT, 2010	atopaxar	placebo			Exploratory	-
LANCELOT ACS	atopaxar	placebo			Exploratory	-
clopidogrel
COMMIT, 2005      NCT	clopidogrel	placebo			Low risk of bias	suggesting
CLARITY-TIMI 28, 2005	clopidogrel	placebo			Low risk of bias	-
CURE, 2001	clopidogrel + aspirin	aspirin			Low risk of bias	suggesting
CURRENT OASIS 7 (clopidogrel), 2010    NCT	clopidogrel high-dose regimen	clopidogrel standard-dose			Low risk of bias	negative
dipyridamol
Prandoni, 1991	aspirin + dipyridamol	placebo			Low risk of bias	negative
elinogrel
ERASE-MI, 2009	elinogrel	placebo			Low risk of bias	negative
prasugrel
TRILOGY ACS (overall population), 2012        NCT	prasugrel	clopidogrel			Low risk of bias	negative
TRITON-TIMI 38, 2007      NCT	prasugrel	clopidogrel			Low risk of bias	suggesting
sulfinpyrazone
Dutch sulphinpyrazone, 1986	sulfinpyrazone	control				negative
Canadian (sulfinpyrazone alone), 1985	sulfinpyrazone	placebo			Low risk of bias	-
Wilcox, 1980	sulfinpyrazone	placebo				negative
Louvain sulphinpyrazone, 1983	sulfinpyrazone	placebo			Low risk of bias	negative
ticagrelor
PLATO, 2009      NCT	ticagrelor	clopidogrel			Low risk of bias	suggesting
DISPERSE-2 (90mg), 2007	ticagrelor	clopidogrel			Low risk of bias	negative
ticlopidine
STAI, 1990	ticlopidine	control				suggesting
Knudsen-A, 1985	ticlopidine	control				negative
Florida UA	ticlopidine	placebo				negative
trapidil
Modena	trapidil	placebo				suggesting
triflusal
Plaza, 1993	triflusal	placebo			Low risk of bias	suggesting
vorapaxar
TRACER, 2011      NCT	vorapaxar	placebo (on top standard therapy)			Low risk of bias	-
antithrombotics
not classified
Gurfinkel (LMWH+asp vs asp), 1995	LMWH	placebo (on top of aspirin)				suggesting
CURRENT - OASIS 7 (ASA), 2010    NCT	ASA high dose	ASA low dose			Risk of bias	suggesting
Gurfinkel (LMWH+asp vs UFH+asp), 1995	LMWH	UFH (on top of aspirin)				suggesting
apixaban
APPRAISE-1 (10mg od), 2009      NCT	apixaban	placebo			Low risk of bias	negative
APPRAISE-1 (2.5 mg bid), 2009      NCT	apixaban	placebo			Low risk of bias	negative
APPRAISE 2, 2011      NCT	apixaban	placebo			Low risk of bias	negative
argatroban
ARGAMI-2, 1998	Argatroban	heparin				-
aspirin
ATACS-pilot, 1990	aspirin	control				negative
VA-pilot	aspirin	placebo				negative
VA-main, 1983	aspirin	placebo			Low risk of bias	suggesting
RISC, 1990	aspirin	placebo			Low risk of bias	suggesting
ALDUSA-pilot	aspirin	placebo				negative
Théroux, 1988	aspirin	placebo			Low risk of bias	suggesting
Canadian (Aspirin vs PBO), 1985	aspirin	placebo			Low risk of bias	-
Canadian (Aspirin + sulfinpyrazone), 1985	aspirin + sulfinpyrazone	placebo			Low risk of bias	negative
atopaxar
LANCELOT ACS	atopaxar	placebo			Exploratory	-
J-LANCELOT, 2010	atopaxar	placebo			Exploratory	-
bivalirudin
ACUITY (biva alone vs hep+aGP2b3a), 2006      NCT	bivalirudin	heparin + GP2b3a inhibitors			Low risk of bias	suggesting
ACUITY (biva+aGP2b3a vs hep+aGP2b3a), 2006    NCT	bivalirudin + GP2b3a inhibitors	heparin + GP2b3a inhibitors			Low risk of bias	negative
PROTECT-TIMI 30, 2006      NCT	bivalirudin	eptifibatide + heparin			Exploratory	-
HERO, 1997	bivalirudin	heparin			Low risk of bias	suggesting
BAT (Bittl), 1995	bivalirudin	heparin			Low risk of bias	suggesting
ACUITY (sub groups PCI, bivalirudin alone) importé, 2007	bivalirudin	heparin + GP2b3a inhibitors				suggesting
ACUITY (sub groups PCI, bivalirudin +aGP2b3a) importé, 2007	bivalirudin + GP2b3a inhibitors	heparin + GP2b3a inhibitors				negative
clopidogrel
CURE (PCI sub study), 2001	clopidogrel	placebo			Low risk of bias	-
CURE, 2001	clopidogrel + aspirin	aspirin			Low risk of bias	suggesting
CURRENT OASIS 7 (clopidogrel), 2010    NCT	clopidogrel high-dose regimen	clopidogrel standard-dose			Low risk of bias	negative
coumadin
ASPECT-2 (coumadin+asp vs asp), 2002	coumadin	control (on top of aspirin)				suggesting
ASPECT-2 (coumadin vs aspirin), 2002	coumadin	aspirin				suggesting
dalteparin
FRISC (long term), 1996	dalteparin	placebo (on top of aspirin)			Low risk of bias	suggesting
FRIC prolonged treatment phase (LWMH vs PBO), 1997	dalteparin	placebo (on top of aspirin)			Low risk of bias	negative
FRISC (short term), 1996	dalteparin	placebo (on top of aspirin)			Low risk of bias	-
FRIC (acute phase LMWH vs UFH), 1997	dalteparin	UFH (on top of aspirin)			Exploratory	negative
dipyridamol
Prandoni, 1991	aspirin + dipyridamol	placebo			Low risk of bias	negative
Efegatran
Klootwijk, 1999	Efegatran	heparin			Exploratory	-
enoxaparin
RESCUE    NCT	enoxaparin	unfractionated heparin				-
EVET, 2005	enoxaparin	tinzaparin				suggesting
ESSENCE, 1997	enoxaparin	UFH (on top of aspirin)			Low risk of bias	suggesting
TIMI 11 B (short term), 1998	enoxaparin	UFH (on top of aspirin)			Low risk of bias	suggesting
SYNERGY, 2005          NCT	enoxaparin	UFH (on top of aspirin)				negative
INTERACT, 2006	enoxaparin	UFH (on top of aspirin)				suggesting
TIMI 11 B (long term), 1998	enoxaparin	UFH (on top of aspirin)			Low risk of bias	negative
fondaparinux
PENTUA, 2004	fondaparinux	enoxaparin				-
OASIS 5, 2006      NCT	fondaparinux	enoxaparin			Low risk of bias	-
hirudin
HIT-4, 1999	Hirudin	heparin			Low risk of bias	-
TIMI 9B, 1996	Hirudin	heparin			Risk of bias	-
GUSTO IIB, 1996	Hirudin	heparin			Risk of bias	-
OASIS pilot, 1997	Hirudin	heparin			Exploratory	-
HELVETICA (Serruys), 1995	Hirudin	heparin			Low risk of bias	-
OASIS 2, 1999	Hirudin	heparin			Low risk of bias	-
OASIS, 1997	Hirudin	heparin			Risk of bias	-
inogatran
TRIM, 1997	Inogatran	heparin			Low risk of bias	-
nadroparin
FRAXIS (6days), 1998	nadroparin	UFH (on top of aspirin)			Low risk of bias	negative
FRAXIS (14 days), 1998	nadroparin	UFH (on top of aspirin)			Low risk of bias	negative
otamixaban
SEPIA-ACS1 TIMI 42, 2009    NCT	otamixaban	unfractionated heparin			Low risk of bias	suggesting
prasugrel
TRILOGY ACS (overall population), 2012        NCT	prasugrel	clopidogrel			Low risk of bias	negative
TRITON-TIMI 38, 2007      NCT	prasugrel	clopidogrel			Low risk of bias	suggesting
rivaroxaban
ATLAS ACS 2 - TIMI 51 (2.5mg), 2011      NCT	rivaroxaban 2.5mg	placebo			Low risk of bias	suggesting
ATLAS ACS 2 - TIMI 51 (5mg), 2011      NCT	rivaroxaban 5mg	placebo				suggesting
sulfinpyrazone
Canadian (sulfinpyrazone alone), 1985	sulfinpyrazone	placebo			Low risk of bias	-
ticagrelor
PLATO, 2009      NCT	ticagrelor	clopidogrel			Low risk of bias	suggesting
DISPERSE-2 (90mg), 2007	ticagrelor	clopidogrel			Low risk of bias	negative
ticlopidine
STAI, 1990	ticlopidine	control				suggesting
Florida UA	ticlopidine	placebo				negative
trapidil
Modena	trapidil	placebo				suggesting
triflusal
TIM, 2000	triflusal	aspirin			Low risk of bias	-
Plaza, 1993	triflusal	placebo			Low risk of bias	suggesting
UFH
Holdright, 1994	UFH	control (on top of aspirin)				negative
RISC (heparin+aspirin vs ASP), 1990	UFH	control (on top of aspirin)				negative
Theroux (heparin+ASP vs ASP), 1988	UFH	control (on top of aspirin)			Low risk of bias	suggesting
ATACS (Cohen), 1994	UFH, warfarin	control (on top of aspirin)				negative
Cohen (ATACS pilot) (heparin+aspirin vs asp), 1990	UFH, warfarin	control (on top of aspirin)				negative
Theroux (heparin vs PBO), 1988	UFH	placebo			Low risk of bias	suggesting
RISC (heparin vs PBO), 1990	UFH	placebo				negative
Theroux (heparin+aspirin vs PBO), 1988	UFH + aspirin	placebo			Low risk of bias	suggesting
RISC (ASP+ heparin vs PBO), 1990	UFH + aspirin	placebo				suggesting
Gurfinkel (UFH+aspririn vs aspirin), 1995	UFH	placebo (on top of aspirin)			Low risk of bias	negative
Cohen (ATACS pilot) (heparin vs asp), 1990	UFH, warfarin	aspirin				negative
vorapaxar
TRACER, 2011      NCT	vorapaxar	placebo (on top standard therapy)			Low risk of bias	-
warfarin
ATACS (pilot study) (warfarin vs control), 1990	warfarin	control (on top of aspirin)				negative
ATACS, 1994	warfarin	control (on top of aspirin)				negative
CARS, 1997	warfarin	control (on top of aspirin)				negative
OASIS Pilot (phase 1), 1998	warfarin	control (on top of aspirin)				negative
OASIS Pilot (phase 2), 1998	warfarin	control (on top of aspirin)				negative
OASIS-2 Warfarin Substudy, 2001	warfarin	control (on top of aspirin)				negative
APRICOT-2, 2002	warfarin	control (on top of aspirin)				negative
CHAMP, 2002	warfarin	control (on top of aspirin)				negative
WARIS, 2002	warfarin	control (on top of aspirin)				suggesting
LoWASA, 2004	warfarin	control (on top of aspirin)				negative
Zibaeenezhad, 2004	warfarin	control (on top of aspirin)				negative
Williams, 1997	warfarin	placebo (on top of aspirin)			Low risk of bias	negative
Huyhn, 2001	warfarin	placebo (on top of aspirin)			Low risk of bias	negative
ATACS (pilot study) warfarin vs aspirin, 1990	warfarin	aspirin				negative
ximelagatran
ESTEEM, 2003	ximelagatran	placebo			Exploratory	-
calcium channel blockers
diltiazem
Göbel (Dutch study), 1995	diltiazem	placebo			Low risk of bias	-
DRS, 1986	diltiazem	placebo			Low risk of bias	-
nifedipine
HINT (nifedipine vs metoprolol), 1988	nifedipine	metoprolol				-
cholesterol lowering intervention
not classified
JAPAN ACS, 2009      NCT	pitavastatin	atorvastatin	acute coronary syndrome	early initiation	Exploratory	-
atorvastatin
MIRACL, 2001	atorvastatin	placebo	acute coronary syndrome	early initiation	Low risk of bias	suggesting
Colivicchi, 2002	atorvastatin	usual care	acute coronary syndrome	early initiation	Exploratory	negative
ESTABLISH, 2004	atorvastatin	usual care	acute coronary syndrome	early initiation	Exploratory	negative
PROVE IT - TIMI 22, 2004	atorvastatin	pravastatin	acute coronary syndrome	early initiation	Low risk of bias	suggesting
ezetimibe
IMPROVE-IT, 2014      NCT	ezetimibe	placebo (on top statins)		early initiation	Low risk of bias	conclusive
fluvastatin
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
pravastatin
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
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
simvastatin
A to Z, 2004	simvastatin	placebo	acute coronary syndrome	early initiation		negative
direct factor Xa inhibitors
apixaban
APPRAISE-1 (10mg od), 2009      NCT	apixaban	placebo			Low risk of bias	negative
APPRAISE-1 (2.5 mg bid), 2009      NCT	apixaban	placebo			Low risk of bias	negative
APPRAISE 2, 2011      NCT	apixaban	placebo			Low risk of bias	negative
dabigatran
REDEEM, 2009    NCT	dabigatran	placebo			Low risk of bias	negative
otamixaban
SEPIA-ACS1 TIMI 42, 2009    NCT	otamixaban	unfractionated heparin			Low risk of bias	suggesting
rivaroxaban
ATLAS ACS 2 - TIMI 51 (2.5mg), 2011      NCT	rivaroxaban 2.5mg	placebo			Low risk of bias	suggesting
ATLAS ACS-TIMI 46 (2.5mg), 2009      NCT	rivaroxaban 2.5mg	placebo			Low risk of bias	negative
ATLAS ACS 2 - TIMI 51 (5mg), 2011      NCT	rivaroxaban 5mg	placebo				suggesting
ATLAS ACS-TIMI 46 (5mg), 2009      NCT	rivaroxaban 5mg	placebo			Low risk of bias	negative
ximelagatran
ESTEEM, 2003	ximelagatran	placebo			Exploratory	-
direct oral anticoagulant (DAO)
apixaban
APPRAISE-1 (10mg od), 2009      NCT	apixaban	placebo			Low risk of bias	negative
APPRAISE-1 (2.5 mg bid), 2009      NCT	apixaban	placebo			Low risk of bias	negative
APPRAISE 2, 2011      NCT	apixaban	placebo			Low risk of bias	negative
dabigatran
REDEEM, 2009    NCT	dabigatran	placebo			Low risk of bias	negative
otamixaban
SEPIA-ACS1 TIMI 42, 2009    NCT	otamixaban	unfractionated heparin			Low risk of bias	suggesting
rivaroxaban
ATLAS ACS 2 - TIMI 51 (2.5mg), 2011      NCT	rivaroxaban 2.5mg	placebo			Low risk of bias	suggesting
ATLAS ACS-TIMI 46 (2.5mg), 2009      NCT	rivaroxaban 2.5mg	placebo			Low risk of bias	negative
ATLAS ACS 2 - TIMI 51 (5mg), 2011      NCT	rivaroxaban 5mg	placebo				suggesting
ATLAS ACS-TIMI 46 (5mg), 2009      NCT	rivaroxaban 5mg	placebo			Low risk of bias	negative
ximelagatran
ESTEEM, 2003	ximelagatran	placebo			Exploratory	-
fibrinolysis
not classified
TAUSA, 1994	intracoronary urokinase	placebo			Low risk of bias	negative
anistreplase
UNASEM, 1992	anistreplase	placebo			Low risk of bias	-
t-pa
Nicklas, 1989	t-PA	placebo			Low risk of bias	negative
Gold, 1987	t-PA	placebo			Exploratory	-
Williams, 1990	t-PA	placebo			Low risk of bias	negative
Freeman, 1992	t-PA	placebo			Low risk of bias	negative
van der Brand, 1991	t-PA	placebo			Low risk of bias	negative
charbonnier, 1992	t-PA	placebo			Low risk of bias	-
Ardissino, 1990	t-PA	placebo			Low risk of bias	negative
TIMI 3B, 1995	t-PA	placebo			Low risk of bias	-
Topol, 1988	t-PA	placebo			Exploratory	negative
TIMI 3A, 1993	t-PA	placebo			Low risk of bias	-
heparin (UFH or LMWH)
not classified
Gurfinkel (LMWH+asp vs asp), 1995	LMWH	placebo (on top of aspirin)				suggesting
Gurfinkel (LMWH+asp vs UFH+asp), 1995	LMWH	UFH (on top of aspirin)				suggesting
dalteparin
FRISC (long term), 1996	dalteparin	placebo (on top of aspirin)			Low risk of bias	suggesting
FRIC prolonged treatment phase (LWMH vs PBO), 1997	dalteparin	placebo (on top of aspirin)			Low risk of bias	negative
FRISC (short term), 1996	dalteparin	placebo (on top of aspirin)			Low risk of bias	-
FRIC (acute phase LMWH vs UFH), 1997	dalteparin	UFH (on top of aspirin)			Exploratory	negative
enoxaparin
RESCUE    NCT	enoxaparin	unfractionated heparin				-
EVET, 2005	enoxaparin	tinzaparin				suggesting
ESSENCE, 1997	enoxaparin	UFH (on top of aspirin)			Low risk of bias	suggesting
TIMI 11 B (short term), 1998	enoxaparin	UFH (on top of aspirin)			Low risk of bias	suggesting
SYNERGY, 2005          NCT	enoxaparin	UFH (on top of aspirin)				negative
INTERACT, 2006	enoxaparin	UFH (on top of aspirin)				suggesting
TIMI 11 B (long term), 1998	enoxaparin	UFH (on top of aspirin)			Low risk of bias	negative
nadroparin
FRAXIS (6days), 1998	nadroparin	UFH (on top of aspirin)			Low risk of bias	negative
FRAXIS (14 days), 1998	nadroparin	UFH (on top of aspirin)			Low risk of bias	negative
UFH
Holdright, 1994	UFH	control (on top of aspirin)				negative
RISC (heparin+aspirin vs ASP), 1990	UFH	control (on top of aspirin)				negative
Theroux (heparin+ASP vs ASP), 1988	UFH	control (on top of aspirin)			Low risk of bias	suggesting
ATACS (Cohen), 1994	UFH, warfarin	control (on top of aspirin)				negative
Cohen (ATACS pilot) (heparin+aspirin vs asp), 1990	UFH, warfarin	control (on top of aspirin)				negative
Theroux (heparin vs PBO), 1988	UFH	placebo			Low risk of bias	suggesting
RISC (heparin vs PBO), 1990	UFH	placebo				negative
Theroux (heparin+aspirin vs PBO), 1988	UFH + aspirin	placebo			Low risk of bias	suggesting
RISC (ASP+ heparin vs PBO), 1990	UFH + aspirin	placebo				suggesting
Gurfinkel (UFH+aspririn vs aspirin), 1995	UFH	placebo (on top of aspirin)			Low risk of bias	negative
Cohen (ATACS pilot) (heparin vs asp), 1990	UFH, warfarin	aspirin				negative
myocardial revascularization
not classified
TAUSA, 1994	intracoronary urokinase	placebo			Low risk of bias	negative
FRISC 2, 1999	routine invasive strategy	concervative strategy				suggesting
TACTICS-TIMI 18, 2001	routine invasive strategy	concervative strategy				suggesting
VINO, 2002	routine invasive strategy	concervative strategy				suggesting
RITA 3, 2002	routine invasive strategy	concervative strategy				suggesting
ICTUS, 2007	routine invasive strategy	concervative strategy				suggesting
TRUCS, 2000	routine invasive strategy	concervative strategy				negative
NQWMI (Eisenberg), 2005	routine invasive strategy	concervative strategy			Exploratory	negative
TACTICS-TIMI 18 elderly (sub group), 2001	routine invasive strategy	concervative strategy				suggesting
TIMI 3B (PTCA), 1994	routine invasive strategy - noncomptemporary	concervative strategy				suggesting
VANQWISH, 1998	routine invasive strategy - noncomptemporary	concervative strategy				suggesting
MATE, 1998	routine invasive strategy - noncomptemporary	concervative strategy				negative
TIMACS, 2009    NCT	early invasive management	delayed invasive strategy			Risk of bias	suggesting
ABOARD, 2009    NCT	immediate invasive management	delayed invasive strategy			Exploratory	negative
OPTIMA, 2009	immediate invasive management	delayed invasive strategy			Risk of bias	suggesting
ISAR-COOL, 2003	early intervention	early strategy				suggesting
VA cooperative, 1987	surgery	medical treatment			Risk of bias	-
anistreplase
UNASEM, 1992	anistreplase	placebo			Low risk of bias	-
t-pa
Nicklas, 1989	t-PA	placebo			Low risk of bias	negative
Gold, 1987	t-PA	placebo			Exploratory	-
Williams, 1990	t-PA	placebo			Low risk of bias	negative
Freeman, 1992	t-PA	placebo			Low risk of bias	negative
van der Brand, 1991	t-PA	placebo			Low risk of bias	negative
charbonnier, 1992	t-PA	placebo			Low risk of bias	-
Ardissino, 1990	t-PA	placebo			Low risk of bias	negative
TIMI 3B, 1995	t-PA	placebo			Low risk of bias	-
Topol, 1988	t-PA	placebo			Exploratory	negative
TIMI 3A, 1993	t-PA	placebo			Low risk of bias	-
New P2Y12 Inhibitors
cangrelor
CHAMPION-PCI, 2009      NCT	cangrelor up front	clopidogrel up front			Low risk of bias	negative
CHAMPION-PLATFORM, 2009    NCT	cangrelor up front	delayed clopidogrel			Low risk of bias	negative
elinogrel
ERASE-MI, 2009	elinogrel	placebo			Low risk of bias	negative
prasugrel
JUMBO-TIMI 26, 2005	prasugrel	clopidogrel			Low risk of bias	negative
TRITON-TIMI 38, 2007      NCT	prasugrel	clopidogrel			Low risk of bias	suggesting
ticagrelor
PLATO, 2009      NCT	ticagrelor	clopidogrel			Low risk of bias	suggesting
DISPERSE-2 (90mg), 2007	ticagrelor	clopidogrel			Low risk of bias	negative
nitrates
nitroglycerin
Doucet, 2000		placebo			Low risk of bias	-
Karlberg, 1998		placebo			Low risk of bias	-
oxygen therapy
not classified
Dekleva, 2004	error	control				negative
Sharifi, 2004	hyperbaric oxygen	control				suggesting
Swift, 1992	hyperbaric oxygen	control				-
Thurston, 1973	hyperbaric oxygen	control				suggesting
Hot MI, 1997	hyperbaric oxygen	control				negative
HOT MI pilot, 1997	Hyperbaric oxygen	control				-
Rawles, 1976	oxygen therapy	control				negative
Ukholkina, 2005	oxygen therapy	control				negative
Wilson, 1997	oxygen therapy	control				negative
AMIHOT II , 2000      NCT	supersaturated oxygen	control				-
AMIHOT, 2007	supersaturated oxygen	control				-
Kerr, 1975	Entonox	placebo			Low risk of bias	-