acute coronary syndrome clinical trials results

anistreplase versus placebo
UNASEM, 1992
anistreplase IV 30 UI over 5 minutes
versus
placebo
Patients without a previous myocardial infarction, with a typical history of unstable angina and ECG abnormalities indicative of ischemia double blind
Follow-up duration: hospital stay, 1y
Europe
apixaban versus placebo
APPRAISE 2, 2011
NCT00831441
apixaban 5mg twice daily
versus
placebo
patients with a recent acute coronary syndrome and at least two additional risk factors for recurrent ischemic eventsdouble blind
Follow-up duration: 8 months
39 countries
APPRAISE-1 (10mg od), 2009
NCT00313300
apixaban 10 mg once daily
versus
placebo
patients with a recent ST-elevation or non–ST-elevation acute coronary syndrome(<7 days) double blind
Follow-up duration: 6 months
Europe, Middle East, North America
APPRAISE-1 (2.5 mg bid), 2009
NCT00313300
Apixaban 2.5mg twice daily
versus
placebo
patients with a recent ST-elevation or non–ST-elevation acute coronary syndrome(<7 days) double blind
Follow-up duration: 6 months
Europe, Middle East, North America
Argatroban versus heparin
ARGAMI-2, 1998
Argatroban 60–20 mg/kg bolus; 2–4 µg /kg/min infusion for 72h
versus
UFH 5000 IU bolus; 1000 IU/h infusion
AMI
Follow-up duration: 30 days
ASA high dose versus ASA low dose
CURRENT - OASIS 7 (ASA), 2010
NCT00335452
High-dose aspirin
versus
Low-dose aspirin
ACS patients referred for an invasive strategy (scheduled for percutaneous coronary intervention no more than 72 hours after randomization) open
Follow-up duration: 30 days
aspirin versus control
Huddinge, 1988
aspirin 500mg/d starting 12 h after admissionand and then intermittently every third day for one month
versus
no aspirin
patients with acute myocardial infarctionopen
Follow-up duration: 30d (12m)
ATACS-pilot, 1990
Aspirin 80mg/d (Heparin + Warfarin)
versus
full-dose heparin followed by warfarin
acute coronary syndromes
Follow-up duration: 3m
Frankfurt, 1976
A1320 + D300, A1320
versus

Follow-up duration: 14d
aspirin versus placebo
VA-main, 1983
Aspirin 324mg/d
versus
placebo
men with unstable angina double blind
Follow-up duration: 3m
ISIS-pilot, 1987
aspirin (325 mg on alternate days for 28 days)
versus
placebo
suspected acute myocardial infarctiondouble blind
Follow-up duration: 1m
ISIS-2, 1988
160 mg/day enteric-coated aspirin for one month
versus
placebo
suspected acute myocardial up to 24hdouble blind
Follow-up duration: 35d
VA-pilot, 0
Aspirin 324 mg/d
versus

Follow-up duration: 3m
RISC, 1990
Aspirin 75mg/d
versus
placebo
men with unstable coronary artery disease (unstable angina or non-Q wave myocardial infarctiondouble blind
Follow-up duration: 12m
Sweden
Canadian (Aspirin vs PBO), 1985
Aspirin 1300mg/d
versus
placebo
patients with unstable angina double blind
Follow-up duration: 18m
ALDUSA-pilot, 0
Aspirin 325mg/d, Aspirin 40mg/d
versus

Follow-up duration: 12m
Dutch-aspirin, 1990
aspirin (100 mg/day) for 3 months
versus
placebo
patients with first anterior wall AMIdouble blind
Follow-up duration: 3m
Théroux, 1988
Aspirin 325 mg twice daily
versus
placebo
acute unstable angina double blind
Follow-up duration: 6d (3m)
APRICOT, 1993
325 mg aspirin daily with discontinuation of heparin
versus
placebo
Patients treated with intravenous thrombolytic therapy followed by intravenous heparin and with patent infarct-related artery demonstrated at angiography within 48 hoursdouble blind
Follow-up duration: 3m
The Netherlands
aspirin + dipyridamol versus placebo
Prandoni, 1991
Aspirin 50mg/d + Dipyridamol 400mg/d
versus
placebo
patients with acute unstable anginadouble blind
Follow-up duration: 12m
aspirin + sulfinpyrazone versus placebo
Canadian (Aspirin + sulfinpyrazone), 1985
Aspirin 1300mg/d + sulfinpyrazone 800mg/d
versus
placebo
patients with unstable angina double blind
Follow-up duration: 18m
atopaxar versus placebo
LANCELOT ACS,
400-mg loading dose of atopaxar followed by a daily dose of 50 mg, 100 mg, or 200 mg for 12 weeks
versus
placebo
unstable-angina or non-STEMI patients
J-LANCELOT, 2010
atopaxar at a loading dose of 400 mg followed by 50 mg per day, 100 mg per day, or 200 mg per day for 12 weeks
versus
atopaxar at a loading dose of 400 mg followed by placebo
patients with acute coronary syndrome (unstable angina and NSTEMI)
Japan
atorvastatin versus placebo
MIRACL, 2001
Atorvastatin, 80 mg (early initiation)
versus
Placebo
unstable angina or non–Q-wave acute MIDouble blind
Follow-up duration: 1 and 4 months
Europe, North America, South Africa, and Australasia
atorvastatin versus pravastatin
PROVE IT - TIMI 22, 2004
80 mg of atorvastatin daily (intensive therapy).
versus
40 mg of pravastatin daily (standard therapy)
patients who had been hospitalized for an acute coronary syndrome within the preceding 10 daysdouble blind
Follow-up duration: 24 mo (18-36 mo)
UK, US, AUstralia, Italy, France, Germany, Spain, Canada
atorvastatin versus usual care
Colivicchi, 2002
Atorvastatin, 80 mg daily early initiation
versus
Usual care
unstable angina pectoris or non-Q-wave myocardial infarctionopen
Follow-up duration: 1, 3, and 6 months
Italy
ESTABLISH, 2004
Atorvastatin, 20 mg early initiation
versus
Usual care
patients with ACS undergoing emergency coronary angiography and percutaneous coronary interventionopen
Follow-up duration: 1, 4, and 6 months
Japan
bivalirudin versus eptifibatide + heparin
PROTECT-TIMI 30, 2006
NCT00250471
bivalirudin alone
versus
eptifibatide plus either unfractionated heparin or enoxaparin
non ST elevation ACS patients undergoing PCIopen
Follow-up duration: hospital stay
International
bivalirudin versus heparin
HERO, 1997
Bivalirudin 0.125–0.250 mg/kg bolus; 0.125–0.500 mg /kg/min infusion for 72h
versus
UFH 5000 IU bolus; 1000–1200 IU/h infusion
AMI (patients presenting within 12 hours with ST-segment elevation)double blind
Follow-up duration: 35 days
BAT (Bittl), 1995
Bivalirudin 1.0 mg/kg bolus; 2.5 mg /kg/h for 4 h, then 0.2 mg /kg/h infusion for 24h
versus
UFH 175 IU/kg bolus; 15 IU mg /kg/h infusion
patients undergoing angioplasty for unstable or postinfarction anginadouble blind
Follow-up duration: 6 months
North America and Europe
bivalirudin versus heparin + GP2b3a inhibitors
ACUITY (biva alone vs hep+aGP2b3a), 2006
NCT00093158
bivalirudin alone
versus
unfractionated heparin or enoxaparin plus a glycoprotein IIb/IIIa inhibitor
in patients with moderate- or high-risk acute coronary syndromes who were undergoing an early invasive strategy.double blind
Follow-up duration: 30 days
17 countries worldwide
ACUITY (sub groups PCI, bivalirudin alone) importé, 2007
bivalirudin alone
versus
heparin (either unfractionated or enoxaparin) plus glycoprotein IIb/IIIa inhibitors
patients with moderate and high-risk acute coronary syndromes undergoing percutaneous coronary intervention after angiography (sub group).open
Follow-up duration: 30 days
bivalirudin + GP2b3a inhibitors versus heparin + GP2b3a inhibitors
ACUITY (biva+aGP2b3a vs hep+aGP2b3a), 2006
NCT00093158
bivalirudin plus a glycoprotein IIb/IIIa inhibitor
versus
unfractionated heparin or enoxaparin plus a glycoprotein IIb/IIIa inhibitor
in patients with moderate- or high-risk acute coronary syndromes who were undergoing an early invasive strategy. double blind
Follow-up duration: 30 days
17 countries worldwide
ACUITY (sub groups PCI, bivalirudin +aGP2b3a) importé, 2007
bivalirudin +
versus
heparin (either unfractionated or enoxaparin) plus glycoprotein IIb/IIIa inhibitors
patients with moderate and high-risk acute coronary syndromes undergoing percutaneous coronary intervention after angiography. open
Follow-up duration: 30 days
cangrelor up front versus clopidogrel up front
CHAMPION-PCI, 2009
NCT00305162
cangrelor up front (cangrelor administered before percutaneous coronary intervention and followed by clopidogrel)
versus
clopidogrel up front (clopidogrel followed by placebo)
high risk patients requiring PCIdouble blind
Follow-up duration: 48 h
14 countries
cangrelor up front versus delayed clopidogrel
CHAMPION-PLATFORM, 2009
NCT00385138
cangrelor up front (cangrelor during PCI followed by 600 mg of clopidogrel)
versus
delayed clopidogrel (placebo during PCI followed by 600 mg of clopidogrel)
patients with acute coronary syndrome undergoing percutaneous coronary intervention double blind
Follow-up duration: 48 h
18 countries
clopidogrel versus placebo
CURE (PCI sub study), 2001
pretreatment with clopidogrel -+aspirin 75–325 mg)
versus
placebo (+ aspirin 75–325 mg)
patients with non-ST-elevation acute coronary syndrome undergoing PCIdouble blind
COMMIT, 2005
NCT00222573
clopidogrel 75 mg daily
versus
placebo
patients admitted to hospital within 24 h of suspected acute MI onset double-blind
Follow-up duration: until discharge or up to 4 wee
CLARITY-TIMI 28, 2005
clopidogrel (300-mg loading dose, followed by 75 mg once daily)
versus
placebo
patients, 18 to 75 years of age, within 12 hours after the onset of an ST-elevation myocardial infarction double blind
Follow-up duration: 30 days
clopidogrel + aspirin versus aspirin
CURE, 2001
clopidogrel 300 mg immediately, followed by 75 mg once daily + aspirin for 3 to 12 months
versus
aspirin (+placebo)
acute coronary syndromes without ST-segment elevation within 24 hours after the onset of symptomsdouble blind
Follow-up duration: NA (median <9 months)
28 countries
clopidogrel high-dose regimen versus clopidogrel standard-dose
CURRENT OASIS 7 (clopidogrel), 2010
NCT00335452
Double-dose clopidogrel
versus
Standard-dose clopidogrel
ACS patients referred for an invasive strategy (scheduled for percutaneous coronary intervention no more than 72 hours after randomization)open
Follow-up duration: 30 days
coumadin versus aspirin
ASPECT-2 (coumadin vs aspirin), 2002
coumadin (phenprocoumon or acenocoumarol) target INR 3-4)
versus
aspirin 80mg daily
UA, AMI open
Follow-up duration: 1 year (range 0-26 months)
the Netherlands
coumadin versus control (on top of aspirin)
ASPECT-2 (coumadin+asp vs asp), 2002
coumadin(INR mean 2.4) +aspirin
versus
aspirin
UA, AMIopen
Follow-up duration: 1 year
the Netherlands
dabigatran versus placebo
REDEEM, 2009
NCT00621855
dabigatran 4 dosages (50mg twice daily, 75mg twice daily, 110mg twice daily, 150mg twice daily)
versus
placebo
patients with recent acute coronary syndromes (ST- or non-ST-elevation myocardical infarction)double blind
Follow-up duration: 6 months
dalteparin versus placebo (on top of aspirin)
FRIC prolonged treatment phase (LWMH vs PBO), 1997
dalteparin SC 120 i.u./kg twice-daily for 6 days followed by dalteparin 7500UI daily up to day 45 (+aspirin)
versus
unfractionated heparin dose-adjusted intravenous infusion (for at least 48h) then by subcutaneous injection up to day 6 (then placebo) (+aspirin)
Patients with unstable angina or non-Q-wave myocardial infarction double blind
Follow-up duration: 45 days
FRISC (long term), 1996
dalteparin SC 120 IU per kg bodyweight [maximum 10 000 IU] twice daily for 6 days with 7500 IU once daily for 34-45 days +aspirin
versus
matched placebo + aspirin
patients with unstable CAD (unstable angina or non-Q-wave myocardial infarction) within the previous 72 hoursdouble blind
Follow-up duration: 40 days
Sweden
FRISC (short term), 1996
dalteparin SC 120 IU per kg bodyweight [maximum 10 000 IU] twice daily for 6 days with 7500 IU once daily for 34-45 days +aspirin
versus
matched placebo + aspirin
patients with unstable CAD (unstable angina or non-Q-wave myocardial infarction) within the previous 72 hours double blind
Follow-up duration: 6 days
Sweden
dalteparin versus UFH (on top of aspirin)
FRIC (acute phase LMWH vs UFH), 1997
twice-daily weight-adjusted subcutaneous injections of dalteparin (120 i.u./kg) (+aspirin)
versus
dose-adjusted intravenous infusion of unfractionated heparin (+aspirin)
Patients with unstable angina or non-Q-wave myocardial infarction open
Follow-up duration: 6 days
dazoxiben versus control
Jones, 1987
DZ
versus

Follow-up duration: 1m
diltiazem versus placebo
Göbel (Dutch study), 1995
diltiazem intravenously
versus
glyceryl trinitrate intravenously
patients with unstable anginadouble blind
Follow-up duration: ND
DRS, 1986
diltiazem 90 mg every six hours up to 14 days
versus
placebo
patients with non-Q-wave myocardial infarct, 24 to 72 hours after the onset of infarction double blind
Follow-up duration: ND
early intervention versus early strategy
ISAR-COOL, 2003
Prolonged (3 to 5 days) antithrombotic pretreatment (“Cooling-Off” strategy) before intervention
versus
early intervention after pretreatment for less than 6 hours
patients with symptoms of unstable angina plus either ST-segment depression or elevation of cardiac troponin T levelsopen
Follow-up duration: 1 mo
Germany
early invasive management versus delayed invasive strategy
TIMACS, 2009
NCT00552513
early invasive management: angiography within 24 hours followed by PCI or CABG as appropriate
versus
delayed invasive strategy: angiography after 36 hours followed by PCI or CABG as appropriate
patients with unstable angina or non-ST-segment-elevation MI (NSTEMI) open
Follow-up duration: 6 months
30 countries
Efegatran versus heparin
Klootwijk, 1999
Efegatran 0.1–0.3 mg/kg bolus; 0.105–1.200 mg /kg/h infusion for 48h
versus
UFH 5000 IU bolus; 1000 IU/h infusion
patients with unstable anginaopen
Follow-up duration: 30 days
elinogrel versus placebo
ERASE-MI, 2009
elinogrel 10, 20, 40, or 60 mg as a single intravenous bolus
versus
placebo
STEMI patients double blind
Follow-up duration: 30-37 days
enoxaparin versus tinzaparin
EVET, 2005
enoxaparin, 100 IU/kg subcutaneously twice daily +aspirin for 7 days
versus
tinzaparin, 175 IU/kg subcutaneously once daily +aspirin for 7 days
patients with non-ST-segment elevation acute coronary syndromes open
Follow-up duration: 30 days
enoxaparin versus UFH (on top of aspirin)
ESSENCE, 1997
enoxaparin 1mg/kg, twice daily during 48h-8days
versus
continuous intravenous unfractionated heparin
patients with angina at rest or non–Q-wave myocardial infarctionDouble blind
Follow-up duration: 14 days (30 days)
United states, Canada, South America, Europe
INTERACT, 2006
enoxaparin (1 mg/kg subcutaneously twice daily) for 48 hours (+eptifibatide and aspirin)
versus
intravenous UFH (70 U/kg bolus followed by 15 U/kg per hour adjusted to an activated partial thromboplastin time of 1.5-2 times control) for 48 hours (+eptifibatide and aspirin)
high-risk patients with ACS receiving aspirin and eptifibatideopen
Follow-up duration: 30 days (2.5y)
Canada
SYNERGY, 2005
NCT00043784
Enoxaparin 1 mg/kg twice daily
versus
unfractionated heparin
high-risk patients with acute coronary syndromes open
Follow-up duration: 30 days
12 countries
TIMI 11 B (long term), 1998
enoxaprin during both the acute phase (IV) and outpatient phase (SC)
versus
intravenous UFH for >=3 days (followed by subcutaneous placebo injections)
unstable angina/non–Q-wave myocardial infarction double blind
Follow-up duration: 43 days
North America, South America,
TIMI 11 B (short term), 1998
enoxaprin during both the acute phase and outpatient phase
versus
intravenous UFH for >=3 days (followed by subcutaneous placebo injections)
unstable angina/non–Q-wave myocardial infarctiondouble blind
Follow-up duration: 8 days (43 days)
North America, South America,
enoxaparin versus unfractionated heparin
RESCUE,
NCT00077818
Enoxaparin
versus
unfractionated heparin
patients diagnosed with acute coronary syndrome in the emergency department open
Follow-up duration: 30 days
Entonox versus placebo
Kerr, 1975
nitrous oxide 50%/oxygen 50% ('Entonox" analgesic apparatus)
versus
placebo
double-blind
error versus control
Dekleva, 2004

versus
ezetimibe versus control
IMPROVE-IT, 2014
NCT00202878
10 mg/day of ezetimibe and 40 mg/day of simvastatin
versus
simvastatin 40 mg/day
subjects with stabilized high-risk acute coronary syndrome double blind
Follow-up duration: 5.68 years
39 countries
flurbiprofen versus placebo
French, 1993
flurbiprofen 50 mg twice daily
versus
placebo
patients successfully treated for acute MI by thrombolysis and/or coronary angioplasty within 6 h of onset of symptomsdouble blind
Follow-up duration: 6m
fluvastatin versus placebo
LIPS (sub groups), 2002
Fluvastatin, 80 mg
versus
Placebo
patients with unstable angina and successful first percutaneous coronary interventiondouble blind
Follow-up duration: 1, 4, and 6 months
Europe, Canada, and Brazil
FLORIDA, 2002
Fluvastatin, 80 mg (early initiation)
versus
Placebo
patients with an AMI and total cholesterol of <6.5 mmol.ldouble blind
Follow-up duration: 1, 4, and 6 months
The Netherlands
fondaparinux versus enoxaparin
OASIS 5, 2006
NCT00139815
fondaparinux 2.5 mg daily until hospital discharge or for up to eight days
versus
enoxaparin 1 mg per kilogram of body weight twice daily for two to eight days or until the patient was in clinically stable condition
patients with acute coronary syndromesdouble blind
Follow-up duration: 9 days (180 days)
41 countires
PENTUA, 2004
Four doses fondaparinux (2.5, 4, 8, or 12 mg once daily) for three to seven days
versus
enoxaparin (1 mg/kg twice daily) for three to seven days
patients with ACS without persistent ST-segment elevation
Follow-up duration: 9 days
GR3219B versus control
GRAND, 1987
GRB
versus

Follow-up duration: 1m
Hirudin versus heparin
HIT-4, 1999
Hirudin 0.2 mg/kg bolus; 0.5 mg/kg twice daily 0.1 mg/kg 0.1 mg /kg/h infusion for 5-7 days
versus
Placebo bolus, UFH 12 500 IU twice daily
patients with AMI <=6 h were treated with aspirin and streptokinase double blind
Follow-up duration: 30 days
OASIS, 1997
low-dose hirudin (0.2 mg/kg bolus+0.10 mg/kg/h infusion) or medium-dose hirudin (0.4 mg/kg bolus+0.15 mg/kg/h infusion) for 72h
versus
heparin 5000 IU bolus+1000 to 1200 U/h
patients with unstable angina or suspected acute MI without ST-segment elevation open
Follow-up duration: 7 days
TIMI 9B, 1996
Hirudin 0.1 mg/kg bolus; 0.1 mg /kg/h infusion for 96h
versus
UFH 5000 IU bolus; 1000 IU/h infusion
Unstable angina or AMIopen
Follow-up duration: 30 days
GUSTO IIB, 1996
Hirudin 0.1 mg/kg bolus; 0.1 mg /kg/h infusion for 72h
versus
UFH 5000 IU bolus; 1000 IU/h infusion for 72H
patients with acute coronary syndromes open
Follow-up duration: 30days (1 year)
OASIS pilot, 1997
Hirudin 0.2–0.4 mg/kg bolus; 0.10–0.15 mg /kg/h infusion for 72h
versus
UFH 5000 IU bolus; 1000–1200 IU/h infusion
patients with unstable angina or suspected acute MI without ST-segment elevation open
Follow-up duration: 6 months
OASIS 2, 1999
Hirudin 0.4 mg/kg bolus; 0.15 mg /kg/h infusion for 72h
versus
UFH 5000 IU bolus; 15 IU /kg/h infusion
patients with unstable angina or suspected acute myocardial infarction without ST elevation double blind
Follow-up duration: 7 days (6 months)
HELVETICA (Serruys), 1995
Hirudin 40 mg intravenous bolus; 0.2 mg /kg/h infusion for 24 h, then 40 mg or placebo twice daily for 72h
versus
UFH 10 000 IU bolus; 15 IU /kg/h infusion for 24 h, then placebo twice daily
patients with unstable angina who were scheduled for angioplastydouble blind
Follow-up duration: 6 months
hyperbaric oxygen versus control
Sharifi, 2004
hyperbaric oxygen therapy
versus
after percutaneous coronary intervention for acute myocardial infarction or unstable angina pectoris
Swift, 1992
hyperbaric oxygen
versus
patients within 1 week of acute myocardial infarction
Thurston, 1973
hyperbaric oxygen
versus
acute myocardial infarction
Hot MI, 1997
Hyperbaric oxygen
versus
Patients with an acute myocardial infarction who received recombinant tissue plasminogen activator
Hyperbaric oxygen versus control
HOT MI pilot, 1997
Hyperbaric oxygen
versus
Patients with an acute myocardial infarction (AMI) who received recombinant tissue plasminogen activator
immediate invasive management versus delayed invasive strategy
ABOARD, 2009
NCT00442949
immediate catheterization and revascularization
versus
catheterization and revascularization on the next working day (between 8 and 60 hours after enrollment)
patient with non ST-elevation acute coronary syndrome open
Follow-up duration: 1 month
France
OPTIMA, 2009
ISRCTN80874637
immediate angioplasty under triple antiplatelet therapy protection
versus
deferred angioplasty
patients with non-ST-segment elevation acute coronary syndromes eligible for percutaneous coronary interventionopen
Follow-up duration: 30 days
The Netherland, England
Inogatran versus heparin
TRIM, 1997
Inogatran 0.1–5.5 mg bolus; 2.0–10.0 mg/h infusion for 72h
versus
UFH 5000 IU bolus; 1200 IU/h infusion
patients with suspected unstable angina, or non-Q wave myocardial infarctiondouble blind
Follow-up duration: 30 days
intracoronary urokinase versus placebo
TAUSA, 1994
intracoronary urokinase 250000 UI or 500000 UI
versus
placebo
ischemic rest pain with or without a recent (< 1 month) infarction double blind
Follow-up duration: hospital stay
USA
LMWH versus placebo (on top of aspirin)
Gurfinkel (LMWH+asp vs asp), 1995
aspirin plus low molecular weight heparin (214 UIC/kg anti-Xa twice daily subcutaneously
versus
aspirin (200 mg/day
patients with unstable angina single blind
Follow-up duration: 5-7 days
LMWH versus UFH (on top of aspirin)
Gurfinkel (LMWH+asp vs UFH+asp), 1995
aspirin plus low molecular weight heparin (214 UIC/kg anti-Xa twice daily subcutaneously
versus
aspirin plus regular heparin (400 IU/kg body weight per day intravenously and titered by activated partial thromboplastin time
patients with unstable angina single blind
Follow-up duration: 5-7 days
misc. versus control
Gent-AMI, 1968
D400
versus

Follow-up duration: 28d
Johannessen, 1989
A150 + D225
versus

Follow-up duration: 14d
nadroparin versus UFH (on top of aspirin)
FRAXIS (14 days), 1998
nadroparin for 14 days
versus
unfractionated heparin for 14 days
unstable angina or non-Q wave myocardial infraction double blind
Follow-up duration: 14 days
17 countries
FRAXIS (6days), 1998
nadroparin for 6 days (+aspirin)
versus
unfractionated heparin for 6 days (+aspirin)
unstable angina or non-Q wave myocardial infractionDouble blind
Follow-up duration: 14 days
17 countries
nifedipine versus metoprolol
HINT (nifedipine vs metoprolol), 1988
nifedipine
versus
metoprolol
patients with unstable angina not pretreated with a beta-blocker and of nifedipine ND
Follow-up duration: ND
otamixaban versus unfractionated heparin
SEPIA-ACS1 TIMI 42, 2009
NCT00317395
otamixaban 5 doses (0·08 mg/kg bolus followed by 0.035, 0.070, 0.105, 0.140, 0.175 mg/kg/h)
versus
Heparin+eptifibatide
patients with non-ST-elevation acute coronary syndromesdouble blind
Follow-up duration: 7 days
36 countries
oxygen therapy versus control
Rawles, 1976
oxygen administered by MC mask throughout the first 24 hours
versus
air
myocardial infarction
Ukholkina, 2005
oxygenotherapy
versus
patients with acute myocardial infarction
Wilson, 1997
oxygen therapy
versus
control
patients presenting within 24 hours of onset of myocardial infarction
pitavastatin versus atorvastatin
JAPAN ACS, 2009
NCT00242944
pitavastatin 4 mg daily
versus
atorvastatin 20mg daily
patients with acute coronary syndrome undergoing IVUS-guided percutaneous coronary intervention open
Follow-up duration: 8-12 months
Japan
prasugrel versus clopidogrel
TRILOGY ACS (overall population), 2012
NCT00699998
prasugrel 10 mg daily
versus
clopidogrel 75 mg daily
patients with acute coronary syndromes selected for a final treatment strategy of medical management without revascularization within 10 days after the index eventdouble-blind
Follow-up duration: 17 months (median)
52 countries
TRITON-TIMI 38, 2007
NCT00097591
prasugrel 60-mg loading dose and 10-mg daily maintenance dose, for 6 to 15 months
versus
clopidogrel (a 300-mg loading dose and a 75-mg daily maintenance dose) for 6 to 15 months
patients with moderate-to-high-risk acute coronary syndromes (UA, NSTEMI,STEMI) with scheduled percutaneous coronary interventiondouble blind
30 countries
JUMBO-TIMI 26, 2005
Prasugrel 3 doses
versus
clopidogrel 300mg loading dose followed by 75 mg daily)
patients undergoing elective or urgent percutaneous coronary interventiondouble blind
Follow-up duration: 30 days
pravastatin versus placebo
LAMIL, 1997
Pravastatin, 10-20 mg (starting at D3)
versus
Placebo
patients suffering an acute myocardial infarction double blind
Follow-up duration: 1 and 3 months
Belgium
RECIFE, 1999
Pravastatin, 40 mg
versus
Placebo
Patients with acute myocardial infarction or unstable angina and total cholesterol levels at admission >=5.2 mmol/L or LDL >=3.4 mmol/L double blind
Follow-up duration: 1.5 months
Canada
PAIS, 2001
Pravastatin, 40 mg (initiated within 48 hours of hospital admission)
versus
Placebo
patients with acute coronary syndromesdouble blind
Follow-up duration: 1 and 3 months
The Netherlands
PACT, 2004
Pravastatin, 20-40 mg within 24 hours of the onset of symptoms in
versus
Placebo
patients with unstable angina, non-ST-segment elevation myocardial infarction, or ST-segment elevation myocardial infarction within 24 hours of the onset of symptomsdouble blind
Follow-up duration: 1 months
Australia
pravastatin versus usual care
L-CAD, 2000
Pravastatin, 20-40 mg (strating on average at D6)
versus
Usual care
patients with acute coronary syndrome open
Follow-up duration: 1, 4, and 6 months
Germany
PTT, 2002
Pravastatin, 40 mg
versus
Usual care
patients who underwent coronary balloon angioplasty of the infarct-related artery during the first month of acute myocardial infarctionopen
Follow-up duration: 1 and 6 months
Turkey
ranolazine versus placebo
MERLIN TIMI 36, 2007
NCT00099788
ranolazine 1000 mg twice daily for the duration of the trial (intitialy 200 mg intravenously for 1 hour, followed by an 80 mg/h intravenous infusion)
versus
placebo
Hospitalized with NSTE-ACS; ischemic symptoms at rest within 48 hours; and at least one indicator of moderate to high risk, defined as elevated troponin or creatine kinase-myocardial band, ST-depression >0.1 mV, diabetes, or TIMI risk score for unstable angina/NSTEMI >=3Double blind
Follow-up duration: median 11.4 months
17 countries
rivaroxaban 2.5mg versus placebo
ATLAS ACS-TIMI 46 (2.5mg), 2009
NCT00402597
rivaroxaban 2.5 mg twice daily
versus
placebo
recent ACS patients treated with aspirin alone (n=761) or aspirin plus clopidogrel (n=2730) double blind
Follow-up duration: 6 months
27 countries
ATLAS ACS 2 - TIMI 51 (2.5mg), 2011
NCT00809965
rivaroxaban 2.5 mg twice daily in addition to standard care
versus
placebo
patients with a recent ACSdouble blind
Follow-up duration: 13 months
44 countries
rivaroxaban 5mg versus placebo
ATLAS ACS-TIMI 46 (5mg), 2009
NCT00402597
rivaroxaban 5 mg twice daily
versus
placebo
recent ACS patients treated with aspirin alone (n=761) or aspirin plus clopidogrel (n=2730) double blind
Follow-up duration: 6 months
27 countries
ATLAS ACS 2 - TIMI 51 (5mg), 2011
NCT00809965
rivaroxaban 5 mg twice daily in addition to standard care
versus
placebo
patients with a recent ACS double blind
Follow-up duration: 13 months
44 countries
routine invasive strategy versus concervative strategy
ICTUS, 2007
ISRCTN82153174
early invasive strategy
versus
selective invasive treatment strategy
patients with non–ST-segment elevation acutec oronary syndrome and elevated cardiac troponin Topen
Follow-up duration: 12 mo (4y)
Netherlands
FRISC 2, 1999
early invasive treatment strategy: angiography within 7 days aiming for revascularisation
versus
non-invasive treatment strategy: angiography only in patients with refractory or recurrent symptoms despite maximum medical treatment or severe ischemia during exercise test before discharge
patients with non–ST-segment elevation acutecoronary syndromeOpen
Follow-up duration: 24 mo
Scandinavia
NQWMI (Eisenberg), 2005
Invasive (angiography at days 2 to 5)
versus
Noninvasive (stress testing at day 2 to 5)
patients with non–Q-wave myocardial infarctionopen
Follow-up duration: 12 months
Canada
RITA 3, 2002
ISRCTN07752711r
routine angiography followed by revascularisationage/pj
versus
conservative strategy (ischaemia-driven or symptom-driven angiography€S
patients with non–ST-segment elevation acutecoronary syndromeopen
Follow-up duration: 24 mo (60 mo)
UK
TACTICS-TIMI 18, 2001
early invasive management strategy
versus
conservative management strategy
patients with non–ST-segment elevation acute coronary syndromeopen
Follow-up duration: 6 mo
9 countries
TRUCS, 2000
invasive strategy
versus
conservative strategy
patients with non–ST-segment elevation acute coronary syndrome in geographically isolated hospitals without cardiac surgical facilities
Follow-up duration: 12 mo
Greece
VINO, 2002
first day angiography / angioplasty strategy
versus
early conservative therapy
patients with non–ST-segment elevation acute coronary syndromeopen
Follow-up duration: 6 mo
Czech Republic
TACTICS-TIMI 18 elderly (sub group), 2001
early invasive management strategy
versus
conservative management strategy
patients 65 years of age and older with unstable angina and non–STsegment elevation myocardial infarction open
Follow-up duration: 6 mo
9 countries
routine invasive strategy - noncomptemporary versus concervative strategy
MATE, 1998
early triage angiography and subsequent therapies based on the angiogram
versus
conventional medical therapy
acute MI ineligible for thrombolytic therapy within 24 h of symptomsopen
Follow-up duration: 21 mo
US
TIMI 3B (PTCA), 1994
Early invasive strategy: systematic angiography (18-48h after randomisation) and revascularisation (PTCA or CABG)
versus
Early elective strategy: angiography and revascularisation only in case of ischemic recurrence (see paper)
patient with unstable angina or non Q wave MI within 24hrs of onsetOpen
Follow-up duration: 12 mo
USA & Canada
VANQWISH, 1998
invasive management
versus
conservative management: medical therapy with subsequent invasive management if indicated by the development of spontaneous or indicible ischemia within 24-72 hours
Patients with Non–Q-wave myocardial infarctionOpen
Follow-up duration: 23 mo
US
simvastatin versus placebo
A to Z, 2004
Simvastatin, 40-80 mg early initiation
versus
Placebo
patient with an acute coronary syndrome (ACS)Double aveugle
Follow-up duration: 1 and 4 months
41 countries
sulfinpyrazone versus control
Dutch sulphinpyrazone, 1986
S (W)
versus

Follow-up duration: 21d
sulfinpyrazone versus placebo
Canadian (sulfinpyrazone alone), 1985
sulfinpyrazone 800mg/d
versus
placebo
patients with unstable angina double blind
Follow-up duration: 18m
Wilcox, 1980
Sulphinpyrazone 200 mg four times daily
versus
placebo
patients with acute myocardial infarction
Follow-up duration: 10d
Louvain sulphinpyrazone, 1983
sulphinpyrazone, 4 x 200 mg daily for 7 days
versus
placebo
recent myocardial infarction double blind
Follow-up duration: 7d
supersaturated oxygen versus control
AMIHOT II , 2000
NCT00175058
90-minute intracoronary supersaturated oxygen (SSO(2)) infusion in the left anterior descending artery infarct territory
versus
control
patients with anterior ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention within 6 hours of symptom onset
AMIHOT, 2007
hyperoxemic reperfusion for 90 min using intracoronary aqueous oxygen
versus
normoxemic blood autoreperfusion
patients with acute anterior or large inferior AMI undergoing primary or rescue PCI (<24 h from symptom onset) and successful PCI
surgery versus medical treatment
VA cooperative, 1987
coronary-artery bypass surgery plus medical therapy
versus
medical therapy alone
men with unstable angina pectorisopen
Follow-up duration: 2 years (5,10 years)
US
t-PA versus placebo
Nicklas, 1989
rt-PA, 150 mg/8 h
versus
placebo
patients with rest angina, angiographically documented coronary artery disease and pacing-induced ischemiaDouble blind
USA
Gold, 1987
intravenous recombinant human tissue-type plasminogen activator (rt-PA).
versus
placebo
chest pain at rest with transient ST segment deviation of at least 1 mm
Williams, 1990
tissue-type plasminogen activator (rt-PA) (0.75 mg/kg over 1 hour or (0.75 mg/kg over 1 hour; total dose, 100 mg over 6 hours)
versus
placebo
rest angina and angiographic evidence of coronary stenosis double blind
USA
Freeman, 1992
tissue-type plasminogen activator (t-PA) (0.49 MU/kg for 1 hour followed by 0.07 MU/kg per hour for 9 hours)
versus
placebo
patients with unstable angina double blind
Follow-up duration: in hospital
USA
van der Brand, 1991
alteplase 100 mg in 3 h
versus
placebo
patients with angina at rest, despite bedrest and medical treatment double blind
Follow-up duration: hospital stay
The Netherlands
charbonnier, 1992
rt-PA 100 mg/90 minutes (10 mg bolus + 90 mg/90 minutes
versus
placebo
unstable angina pectoris double blind
Ardissino, 1990
recombinant tissue-type plasminogen activator (rt-PA) followed by heparin
versus
heparin alone
unstable angina refractory to conventional medical treatmentdouble blind
Follow-up duration: in hospital
Italy
TIMI 3B, 1995
tissue-type plasminogen activator (t-PA)
versus
placebo
patients with unstable angina and non-Q wave myocardial infarctionDouble blind
Follow-up duration: 1 year
Topol, 1988
intravenous tissue plasminogen activator (t-PA)
versus
placebo
patients with angina at rest and provocable ischemia (pacing induced) open
Follow-up duration: hospital stay
USA
TIMI 3A, 1993
90-minute front-loaded infusion of t-PA (0.8 mg/kg i.v.; maximum, 80 mg)
versus
placebo
patients with unstable angina or non-Q wave myocardial infarctiondouble blind
Follow-up duration: hospital stay
USA, canada
ticagrelor versus clopidogrel
PLATO, 2009
NCT00391872
ticagrelor 90mg twice daily
versus
clopidogrel 75mg once daily
patients with an acute coronary syndrome, with or without ST-segment elevation (onset of symptoms within the previous 24h). double blind
Follow-up duration: 1 y
43 countries
DISPERSE-2 (90mg), 2007
ticagrelor 90 mg twice daily
versus
clopidogrel
patients with NSTE-ACS, treated with aspirin and standard therapy for ACSdouble blind
Follow-up duration: 12 weeks
ticlopidine versus control
STAI, 1990
ticlopidine 250 mg b.i.d
versus
untreated control
patients with unstable angina <=48hrs from the pain onsetsingle blind
Follow-up duration: 6m
Knudsen-A, 1985
ticlopidine 500mg/d
versus
placebo
patients with AMI double blind
Follow-up duration: 3m
ticlopidine versus placebo
Florida UA, 0
Ticlopidine 500mg/d
versus

Follow-up duration: 14d
trapidil versus placebo
Modena, 0
trapidil
versus

Follow-up duration: 6m
triflusal versus aspirin
TIM, 2000
triflusal 600 mg daily
versus
aspirine 300 mg daily
AMI within less than 24 h of symptom onsetedouble blind
Follow-up duration: 35 days
Portugal, Spain, Italy
triflusal versus placebo
Plaza, 1993
triflusal 300 mg three times daily
versus
placebo
patients with unstable anginadouble blind
Follow-up duration: 6m
Spain
UFH versus control (on top of aspirin)
Holdright, 1994
intravenous heparin plus oral aspirin (150 mg once daily)
versus
aspirin alone 150 mg/d
unstable anginasingle blind
Follow-up duration: hospital stay
RISC (heparin+aspirin vs ASP), 1990
5 days of intermittent intravenous heparin + oral aspirin 75 mg/day
versus
oral aspirin 75 mg/day
unstable angina or non-Q-wave myocardial infarctionopen
Follow-up duration: 90 days
Theroux (heparin+ASP vs ASP), 1988
aspirin 325 mg/d + heparin 1000 UI/hr IV
versus
aspirin 325 mg/d
double blind
Follow-up duration: 3-9 days
UFH versus placebo
RISC (heparin vs PBO), 1990
5 days of intermittent intravenous heparin
versus
placebo
men with unstable coronary artery disease (unstable angina or non-Q-wave myocardial infarction)
Follow-up duration: 1y (5,30 and 90 days)
Sweden
Theroux (heparin vs PBO), 1988
heparin (1000 units per hour by intravenous infusion)
versus
placebo
patients with acute unstable angina pectoris double blind
Follow-up duration: 3-9 days
UFH versus placebo (on top of aspirin)
Gurfinkel (UFH+aspririn vs aspirin), 1995
aspirin plus UFH 5000 IU iv then 400 IU/kg body weight per day intravenously and titered by activated partial thromboplastin time
versus
aspirin 200 mg/day
patients greater than 21 years with ustable angina within 24 hours of randomizationcatiodouble blind
Follow-up duration: 5-7 days
UFH + aspirin versus placebo
RISC (ASP+ heparin vs PBO), 1990
oral apsirin 75mg/d + intermittent IV heparin 10000UI/d followed by 7500 UI 6-hourly for 4 days
versus
placebo
men with unstable coronary artery disease (unstable angina or non-Q-wave myocardial infarction)
Follow-up duration: 1y (5,30 and 90 days)
Sweden
Theroux (heparin+aspirin vs PBO), 1988
heparin (1000 units per hour by intravenous infusion)+ aspirin (325 mg twice daily)
versus
aspirin (325 mg twice daily)
double blind
Follow-up duration: 3-9 days
UFH, warfarin versus aspirin
Cohen (ATACS pilot) (heparin vs asp), 1990
heparin followed by warfarin (without aspirin)
versus
aspirin 325 mg/day
Patients between 21 and 75 years with unstable angina or non-Q-wave MI with last episode of pain within 48 hours of screeningopen
Follow-up duration: 12 weeks
UFH, warfarin versus control (on top of aspirin)
ATACS (Cohen), 1994
aspirin 162.5 mg daily plus heparin (activated partial thromboplastin time, two times control) followed by aspirin 162.5 mg daily plus warfarin (international normalized ratio, 2 to 3) for 12 weeks.
versus
aspirin alone (162.5 mg daily) for 12 weeks.
patients with unstable rest angina or non-Q-wave myocardial infarction with last episode of pain within 48 hours of randomization and who were nonprior aspirin userssingle blind
Follow-up duration: 12 weeks
Cohen (ATACS pilot) (heparin+aspirin vs asp), 1990
aspirin (80 mg/day) plus heparin and then warfarin
versus
aspirin (325 mg/day)
Patients between 21 and 75 years with unstable angina or non-Q-wave MI with last episode of pain within 48 hours of screening.open
Follow-up duration: 12 weeks
vorapaxar versus placebo (on top standard therapy)
TRACER, 2011
NCT00527943
vorapaxar (SCH 530348) oral tablets; 40-mg loading dose on first day, followed by 2.5 mg once daily for at least 1 year
versus
Placebo (added to the existing standard of care (eg, aspirin, clopidogrel)
patients with acute coronary syndromedouble-blind
warfarin versus aspirin
ATACS (pilot study) warfarin vs aspirin, 1990
heparin/warfarin target INR 3-4
versus
aspirin 325 mg daily
UA, NSTEMIopen
Follow-up duration: 3 months
warfarin versus control (on top of aspirin)
ATACS (pilot study) (warfarin vs control), 1990
heparin/warfarin target INR 3-4.5 + aspirin
versus
aspirin alone
UA, NSTEMIopen
Follow-up duration: 3 months
ATACS, 1994
heparin/warfarin (INR median 2.3) + aspirin
versus
aspirin
UA, NSTEMIopen
Follow-up duration: 3 months
CARS, 1997
warfarin (INR mean 1.5) (3 mg warfarin or 1 mg warfarin with 80 mg aspirin)
versus
aspirin 160 mg/d
AMI
Follow-up duration: 14 months
OASIS Pilot (phase 1), 1998
warfarin 3mg/d for 6 months (INR mean 1.5)
versus
control
UA, NSTEMIopen
Follow-up duration: 6 months
OASIS Pilot (phase 2), 1998
warfarin adjusted dose (INR mean 2.3) for 3 months
versus
standard treatment
UA, NSTEMIopen
Follow-up duration: 3 months
OASIS-2 Warfarin Substudy, 2001
warfarin target INR 2–2.5 for 5 months +aspirin
versus
control
UAopen
Follow-up duration: 5 months
APRICOT-2, 2002
moderate-intensity coumarin target INR 2-3 (+aspirin)
versus
aspirin
STEMI
Follow-up duration: 3 months
CHAMP, 2002
warfarin (INR median 1.8)
versus
AMI
Follow-up duration: 2.7 years
WARIS, 2002
warfarin (INR 2.2 (mean)
versus
AMI
Follow-up duration: 4 years
LoWASA, 2004
warfarin (prothrombin complex activity mean 95.5)
versus
AMI
Follow-up duration: 5 years
Zibaeenezhad, 2004
Warfarin target INR 2–3
versus
AMI
Follow-up duration: 1 year
warfarin versus placebo (on top of aspirin)
Williams, 1997
warfarin target INR 2–2.5 +aspirin
versus
placebo +aspirin
UA, AMIdouble blind
Follow-up duration: 2.5 months
Huyhn, 2001
warfarin adjusted dose for INR 2–2.5 +aspirin
versus
placebo +aspirin
UA, NSTEMI with prior CABGdouble blind
Follow-up duration: 1 year
ximelagatran versus placebo
ESTEEM, 2003
oral ximelagatran at doses of 24 mg, 36 mg, 48 mg, or 60 mg twice daily
versus
placebo
patients who had had recent ST-elevation or non-STelevation myocardial infarctiondouble-blind
Follow-up duration: 6 months