pathology | Benefit (demonstrated or suggested) and harm | | | |
---|
acute coronary syndrome | All results are NS for efficacy inferior to placebo in terms of Major bleeds in CURE, 2001 inferior to placebo in terms of Major bleeds in CURRENT OASIS 7 (clopidogrel), 2010 | meta-analysis | | Trial | control | p<0.05 | harm | NS |
---|
COMMIT, 2005 | vs placebo | non fatal MI 0.82 [0.70; 0.96] vascular events 0.92 [0.87; 0.97] | | non fatla stroke 0.89 [0.70; 1.13] | CURE, 2001 | vs placebo | Vasc events 0.82 [0.73; 0.90] fatal and non fatal MI 0.78 [0.68; 0.90] cardiovascular events 0.82 [0.73; 0.90] | Major bleeds 1.38 [1.13; 1.67] | Vasc deaths 0.93 [0.80; 1.08] Non vasc deaths 0.92 [0.60; 1.40] fatala and non fatal stroke 0.87 [0.64; 1.18] refractory ischemia 0.93 [0.83; 1.04] fatal bleeding 0.74 [0.34; 1.61] | CURE (PCI sub study), 2001 | vs placebo | | | | CURRENT OASIS 7 (clopidogrel), 2010 | vs placebo | | Major bleeds 1.24 [1.05; 1.46] | vascular death, MI, stroke 0.94 [0.83; 1.06] Severe recurrent ischemia 0.93 [0.64; 1.36] Hemorrhagic stoke 0.67 [0.19; 2.37] Vasc events 0.94 [0.84; 1.06] all cause death 0.96 [0.82; 1.13] Vasc deaths 0.95 [0.81; 1.13] fatala and non fatal stroke 0.99 [0.70; 1.39] fatal and non fatal MI 0.86 [0.72; 1.02] cardiovascular events 0.94 [0.84; 1.06] fatal bleeding 1.07 [0.53; 2.16] | | vs placebo | | | |
Trial | Treatments | Patients | Method |
---|
COMMIT, 2005 | clopidogrel 75 mg daily (n=22961) vs. placebo (n=22891) | patients admitted to hospital within 24 h of suspected acute MI onset | double-blind Parallel groups Sample size: 22961/22891 Primary endpoint: death, reinfarction, or stroke FU duration: until discharge or up to 4 wee | CURE, 2001 | clopidogrel 300 mg immediately, followed by 75 mg once daily + aspirin for 3 to 12 months (n=6259) vs. aspirin (+placebo) (n=6303) | acute coronary syndromes without ST-segment elevation within 24 hours after the onset of symptoms | double blind Parallel groups Sample size: 6259/6303 Primary endpoint: CV death, MI, stroke FU duration: NA (median <9 months) | CURE (PCI sub study), 2001 | pretreatment with clopidogrel -+aspirin 75–325 mg) (n=1313) vs. placebo (+ aspirin 75–325 mg) (n=1345) | patients with non-ST-elevation acute coronary syndrome undergoing PCI | double blind Parallel groups Sample size: 1313/1345 Primary endpoint: ardiovascular death, MI, or urgent TVR FU duration: | CURRENT OASIS 7 (clopidogrel), 2010 | Double-dose clopidogrel (n=12520) vs. Standard-dose clopidogrel (n=12566) patients were also assigned in an open-label manner to 300 to 325 mg of aspirin once daily or 75- to 100-mg aspirin once daily | ACS patients referred for an invasive strategy (scheduled for percutaneous coronary intervention no more than 72 hours after randomization) about two thirds eventually underwent PCI (although PCI was planned for everyone who was randomized, about a third of the patients did not undergo the procedure because they were not considered suitable based on angiography findings) | open Factorial plan Sample size: 12520/12566 Primary endpoint: CV death/MI/stroke FU duration: 30 days | CLARITY-TIMI 28, 2005 | clopidogrel (300-mg loading dose, followed by 75 mg once daily)
(n=-9) vs. placebo
(n=-9)
| patients, 18 to 75 years of age, within 12 hours after the onset of an ST-elevation myocardial infarction
| double blind Sample size: -9/-9 Primary endpoint: death, reMI, occlusion FU duration: 30 days
|
|
acute myocardial infarction | All results are NS for efficacy | meta-analysis | | Trial | control | p<0.05 | harm | NS |
---|
COMMIT, 2005 | vs placebo | non fatal MI 0.82 [0.70; 0.96] vascular events 0.92 [0.87; 0.97] | | non fatla stroke 0.89 [0.70; 1.13] | | vs placebo | | | |
Trial | Treatments | Patients | Method |
---|
COMMIT, 2005 | clopidogrel 75 mg daily (n=22961) vs. placebo (n=22891) | patients admitted to hospital within 24 h of suspected acute MI onset | double-blind Parallel groups Sample size: 22961/22891 Primary endpoint: death, reinfarction, or stroke FU duration: until discharge or up to 4 wee | CLARITY-TIMI 28, 2005 | clopidogrel (300-mg loading dose, followed by 75 mg once daily)
(n=-9) vs. placebo
(n=-9)
| patients, 18 to 75 years of age, within 12 hours after the onset of an ST-elevation myocardial infarction
| double blind Sample size: -9/-9 Primary endpoint: death, reMI, occlusion FU duration: 30 days
|
|
atrial fibrillation | All results are NS for efficacy inferior to anticoagulant in terms of stroke,systemic embolism,major haemorrhage and vascular death in ACTIVE W, 2006 inferior to anticoagulant in terms of non fatal TE events,bleedings and vascular death* in ACTIVE W, 2006 inferior to anticoagulant in terms of all bleeding in ACTIVE W, 2006 inferior to anticoagulant in terms of minor bleeding in ACTIVE W, 2006 inferior to anticoagulant in terms of thrombo-embolic event (cerebral or systemic) in ACTIVE W, 2006 inferior to anticoagulant in terms of ischemic stroke in ACTIVE W, 2006 inferior to anticoagulant in terms of All stroke(ischemic+hemorrhagic/fatal+non fatal) in ACTIVE W, 2006 inferior to anticoagulant in terms of all bleeding in ACTIVE A, 2009 inferior to anticoagulant in terms of major bleeding in ACTIVE A, 2009 inferior to anticoagulant in terms of minor bleeding in ACTIVE A, 2009 inferior to anticoagulant in terms of intracranial hemorrhage(hemorrhagic stroke+hematomas) in ACTIVE A, 2009 | meta-analysis | | Trial | control | p<0.05 | harm | NS |
---|
ACTIVE W, 2006 | vs anticoagulant | haemorragic stroke(or intracerebral hemorrhage) 0.34 [0.12; 0.93] | stroke,systemic embolism,major haemorrhage and vascular death 1.39 [1.18; 1.64] non fatal TE events,bleedings and vascular death* 1.39 [1.18; 1.64] all bleeding 1.17 [1.06; 1.30] minor bleeding 1.19 [1.07; 1.33] thrombo-embolic event (cerebral or systemic) 1.43 [1.18; 1.74] ischemic stroke 2.17 [1.51; 3.11] All stroke(ischemic+hemorrhagic/fatal+non fatal) 1.71 [1.25; 2.36] | non vascular death 0.76 [0.50; 1.15] all death 1.02 [0.82; 1.26] vascular death 1.14 [0.89; 1.48] major bleeding 1.10 [0.83; 1.45] fatal stroke(ischemic+hemorrhagic) 0.94 [0.46; 1.95] fatal bleeding 0.64 [0.25; 1.66] | ACTIVE A, 2009 | vs anticoagulant | fatal stroke(ischemic+hemorrhagic) 0.72 [0.59; 0.88] thrombo-embolic event (cerebral or systemic) 0.90 [0.83; 0.98] ischemic stroke 0.69 [0.59; 0.81] thromboembolic event likes(TE event or ischemic stroke or systemic embolism) 0.89 [0.89; 0.89] All stroke(ischemic+hemorrhagic/fatal+non fatal) 0.73 [0.63; 0.84] | all bleeding 1.56 [1.43; 1.70] major bleeding 1.57 [1.29; 1.91] minor bleeding 2.34 [1.97; 2.77] intracranial hemorrhage(hemorrhagic stroke+hematomas) 1.87 [1.19; 2.93] | all death 0.98 [0.90; 1.07] vascular death 1.00 [0.91; 1.11] haemorragic stroke(or intracerebral hemorrhage) 1.37 [0.79; 2.37] fatal bleeding 1.56 [0.96; 2.52] myocardial infarction 0.78 [0.60; 1.03] |
Trial | Treatments | Patients | Method |
---|
ACTIVE W, 2006 | clopidogrel (75 mg per day) plus aspirin (75–100 mg per day) (n=3335) vs. oral anticoagulation therapy (target international normalised ratio of 2·0–3·0) (n=3371) | Patients with atrial fibrillation plus one or more risk factor for stroke | open Parallel groups Sample size: 3335/3371 Primary endpoint: stroke, non-CNS systemic embolus FU duration: 1.28 y (median) | ACTIVE A, 2009 | clopidogrel 75 mg daily + aspirin 75-100 mg daily (n=3772) vs. aspirin 75-100 mg daily alone (n=3782) | Patients with AF and at least one risk factor for stroke and who are not candidates for warfarin therapy | double blind Parallel groups Sample size: 3772/3782 Primary endpoint: stroke, MI, systemic embolus, or vascular death FU duration: 3.7 y |
|
CABG surgery | All results are NS for efficacy | meta-analysis | | Trial | control | p<0.05 | harm | NS |
---|
CASCADE, 2009 | vs aspirin | | | |
Trial | Treatments | Patients | Method |
---|
CASCADE, 2009 | aspirin 162 mg plus clopidogrel 75 mg daily for 1 year (n=56) vs. aspirin 162 mg plus placebo daily (n=57) | patients after CABG involving at least two saphenous vein grafts | double blind Parallel groups Sample size: 56/57 Primary endpoint: vein graft intimal area FU duration: 1 y |
|
cardiovascular prevention | All results are NS for efficacy inferior to aspirin in terms of moderate bleeding in CHARISMA, 2006 (secondary prevention patients) | meta-analysis | | Trial | control | p<0.05 | harm | NS |
---|
CAPRIE (PAD subgroup), 1996 | vs aspirin | IDM fatal 0.62 [0.44; 0.88] IDM totaux 0.63 [0.47; 0.85] | | Mortalité totale 0.81 [0.63; 1.06] AVC fatal 0.95 [0.69; 1.31] AVC non fatal 1.38 [0.55; 3.42] IDM non fatal 0.67 [0.37; 1.21] | CAPRIE, 1996 | vs aspirin | Non fatal MI 0.84 [0.70; 1.00] MI,stroke or CVdeath 0.92 [0.84; 1.00] | | Death from any cause 0.98 [0.87; 1.10] Death from cardiovascular causes 0.92 [0.80; 1.07] severe bleeding 0.88 [0.70; 1.12] non fatal stroke 0.94 [0.82; 1.07] | CHARISMA, 2006 | vs aspirin | non fatal stroke 0.81 [0.65; 1.00] | moderate bleeding 1.62 [1.27; 2.08] | nonfatal Ischemic stroke 0.82 [0.66; 1.04] Death from any cause 0.99 [0.86; 1.14] Death from cardiovascular causes 1.04 [0.87; 1.24] severe bleeding 1.25 [0.97; 1.61] Non fatal MI 0.92 [0.74; 1.15] fatal bleeding 1.53 [0.83; 2.82] MI,stroke or CVdeath 0.93 [0.83; 1.04] | ASCET | vs aspirin | | | vascular event 0.90 [0.63; 1.29] |
Trial | Treatments | Patients | Method |
---|
CAPRIE (PAD subgroup), 1996 | Clopidogrel 75 mg (n=3223) vs. Aspirine 325 mg (n=3229) | patients with atherosclerotic vascular disease manifested as either recent ischaemic stroke, recent myocardial infarction, or symptomatic peripheral arterial disease Effectifs correspondant à la strate AOMI | double blind Parallel groups Sample size: 3223/3229 Primary endpoint: Critère composite FU duration: 1.91 y | CAPRIE, 1996 | clopidogrel 75 mg once daily (n=9599) vs. aspirin 325 mg once daily (n=9586) | patients with atherosclerotic vascular disease manifested as either recent ischaemic stroke, recent myocardial infarction, or symptomatic peripheral arterial disease | Double blind Parallel groups Sample size: 9599/9586 Primary endpoint: ischaemic stroke, myocardial infarction, or vascular death FU duration: mean 1.91 years | CHARISMA, 2006 | clopidogrel (75 mg per day) plus low-dose aspirin (75 to 162 mg per day) (n=7802) vs. placebo plus low-dose aspirin (n=7801) | patients with either clinically evident cardiovascular disease or multiple risk factors | Double blind Parallel groups Sample size: 7802/7801 Primary endpoint: myocardial infarction, stroke or death from cardiovasculare causes FU duration: median 28 months | ASCET | clopidogrel 75 mg once daily for two years (n=498) vs. Aspirin 160 mg once daily for two years (n=503) | patients with documented coronary heart disease and treated with aspirin platelet function was also assessed at randomization with the PFA100 method and platelet aggregometry | open Parallel groups Sample size: 498/503 Primary endpoint: all-cause death, nonfatal MI, ischemic stroke, and unstable angina FU duration: |
|
coronary artery disease | All results are NS for efficacy | meta-analysis | | Trial | control | p<0.05 | harm | NS |
---|
CAPRIE, 1996 | vs aspirin | | | | ASCET | vs aspirin | | | vascular event 0.90 [0.63; 1.29] |
Trial | Treatments | Patients | Method |
---|
CAPRIE, 1996 | Clopidogrel (75 mg) 1x/d for a minimum of one year and a maximum of 3 years (n=9599) vs. Aspirin (325 mg) 1x/d (n=9586) | patients with atherosclerotic vascular disease manifested as either recent ischaemic stroke, recent myocardial infarction, or symptomatic peripheral arterial disease | Double blind Parallel groups Sample size: 9599/9586 Primary endpoint: ischaemic stroke, myocardial infarction, vascular death FU duration: 1.91 y | ASCET | clopidogrel 75 mg once daily for two years (n=498) vs. Aspirin 160 mg once daily for two years (n=503) | patients with documented coronary heart disease and treated with aspirin platelet function was also assessed at randomization with the PFA100 method and platelet aggregometry | open Parallel groups Sample size: 498/503 Primary endpoint: all-cause death, nonfatal MI, ischemic stroke, and unstable angina FU duration: |
|
percutaneous coronary intervention | All results are NS for efficacy | meta-analysis | | Trial | control | p<0.05 | harm | NS |
---|
Müller, 2000 | vs ticlopidine + aspirin | | | MACE 1.78 [0.67; 4.76] | CLASSICS, 2000 | vs ticlopidine + aspirin | | | MACE 1.31 [0.30; 5.83] | TOPPS, 2001 | vs ticlopidine + aspirin | | | MACE 0.84 [0.46; 1.51] | Piamsomboon, 2001 | vs ticlopidine + aspirin | | | MACE 0.00 [0.00; NaN] | GRAVITAS, 2011 | vs ticlopidine + aspirin | | | all cause death 0.70 [0.27; 1.83] Cardiovascular death 0.37 [0.10; 1.40] MI 1.11 [0.59; 2.08] any bleeding 1.17 [0.93; 1.49] GUSTO severe/moderate bleeding 0.60 [0.32; 1.13] Cardiovascular death/MI/stent thrombosis 1.01 [0.58; 1.76] definite stent thrombosis 0.62 [0.20; 1.90] | REAL-LATE, ZEST-LATE, 2010 | vs ticlopidine + aspirin | | | all cause death 1.52 [0.76; 3.05] major bleeding 2.97 [0.31; 28.51] stroke 2.23 [0.69; 7.21] MI 1.41 [0.54; 3.70] definite stent thrombosis 1.24 [0.33; 4.60] |
Trial | Treatments | Patients | Method |
---|
Müller, 2000 | Clopidogrel 75 mg qD x4 wks Aspirin 100 mg qD (n=355) vs. Ticlopidine 250 mg BID x4 wks Aspirin 100 mg qD (n=345) | | Sample size: 355/345 Primary endpoint: FU duration: | CLASSICS, 2000 | Clopidogrel 300mg x1, 75 mg qD x4 wks Aspirin 325 mg qDypñ ·` (n=345) vs. Ticlopidine 250 mg BID x4 wks Aspirin 325 mg qD (n=340) | | Sample size: 345/340 Primary endpoint: FU duration: | TOPPS, 2001 | Clopidogrel 300 mg x1, unsp. Dose x2 wks Aspirin 325 mg qD (n=494) vs. Ticlopidine 500 mg x1, unsp. Dose x2 wks Aspirin 325 mg qD (n=522) | | Sample size: 494/522 Primary endpoint: FU duration: | Piamsomboon, 2001 | Clopidogrel 300 mg x1, 75 mg qD x4 wks Aspirin 300 mg BID x4 wks, 300 mg qD (n=37) vs. Ticlopidine 250 mg po BID x4 wks Aspirin 300 mg BID x4 wks, 300 mg qD (n=31) | | Sample size: 37/31 Primary endpoint: FU duration: | GRAVITAS, 2011 | High-dose clopidogrel (600-mg initial dose, 150 mg daily thereafter) (n=1109) vs. regular clopidogrel dose (n=1105) | patients receiving drug-eluting stents with high residual platelet activity (PRU>=230) on the regular clopidogrel dose (platelet-function tests with the VerifyNow assay 12 to 24 hours after PCI) | open Parallel groups Sample size: 1109/1105 Primary endpoint: Cardiovascular death/MI/stent thrombosis FU duration: 6 months | REAL-LATE, ZEST-LATE, 2010 | clopidogrel plus aspirin (n=1357) vs. aspirin alone (n=1344) | patients who had received drugeluting
stents and had been free of major adverse cardiac or cerebrovascular events
and major bleeding for a period of at least 12 months | open Parallel groups Sample size: 1357/1344 Primary endpoint: CV death, MI FU duration: 19.2 months |
|
peripheral vascular diseases | All results are NS for efficacy | meta-analysis | | Trial | control | p<0.05 | harm | NS |
---|
CAPRIE (PAD subgroup), 1996 | vs aspirin | IDM fatal 0.62 [0.44; 0.88] IDM totaux 0.63 [0.47; 0.85] | | Mortalité totale 0.81 [0.63; 1.06] AVC fatal 0.95 [0.69; 1.31] AVC non fatal 1.38 [0.55; 3.42] IDM non fatal 0.67 [0.37; 1.21] |
Trial | Treatments | Patients | Method |
---|
CAPRIE (PAD subgroup), 1996 | Clopidogrel 75 mg (n=3223) vs. Aspirine 325 mg (n=3229) | patients with atherosclerotic vascular disease manifested as either recent ischaemic stroke, recent myocardial infarction, or symptomatic peripheral arterial disease Effectifs correspondant à la strate AOMI | double blind Parallel groups Sample size: 3223/3229 Primary endpoint: Critère composite FU duration: 1.91 y |
|
post myocardial infarction | All results are NS for efficacy | meta-analysis | | Trial | control | p<0.05 | harm | NS |
---|
CAPRIE, 1996 | vs aspirin | | | |
Trial | Treatments | Patients | Method |
---|
CAPRIE, 1996 | Clopidogrel (75 mg) 1x/d for a minimum of one year and a maximum of 3 years (n=9599) vs. Aspirin (325 mg) 1x/d (n=9586) | patients with atherosclerotic vascular disease manifested as either recent ischaemic stroke, recent myocardial infarction, or symptomatic peripheral arterial disease | Double blind Parallel groups Sample size: 9599/9586 Primary endpoint: ischaemic stroke, myocardial infarction, vascular death FU duration: 1.91 y |
|
stable angina | All results are NS for efficacy | meta-analysis | | Trial | control | p<0.05 | harm | NS |
---|
ASCET | vs aspirin | | | vascular event 0.90 [0.63; 1.29] |
Trial | Treatments | Patients | Method |
---|
ASCET | clopidogrel 75 mg once daily for two years (n=498) vs. Aspirin 160 mg once daily for two years (n=503) | patients with documented coronary heart disease and treated with aspirin platelet function was also assessed at randomization with the PFA100 method and platelet aggregometry | open Parallel groups Sample size: 498/503 Primary endpoint: all-cause death, nonfatal MI, ischemic stroke, and unstable angina FU duration: |
|
stent | All results are NS for efficacy | meta-analysis | | Trial | control | p<0.05 | harm | NS |
---|
Müller, 2000 | vs ticlopidine + aspirin | | | MACE 1.78 [0.67; 4.76] | CLASSICS, 2000 | vs ticlopidine + aspirin | | | MACE 1.31 [0.30; 5.83] | TOPPS, 2001 | vs ticlopidine + aspirin | | | MACE 0.84 [0.46; 1.51] | Piamsomboon, 2001 | vs ticlopidine + aspirin | | | MACE 0.00 [0.00; NaN] | GRAVITAS, 2011 | vs ticlopidine + aspirin | | | all cause death 0.70 [0.27; 1.83] Cardiovascular death 0.37 [0.10; 1.40] MI 1.11 [0.59; 2.08] any bleeding 1.17 [0.93; 1.49] GUSTO severe/moderate bleeding 0.60 [0.32; 1.13] Cardiovascular death/MI/stent thrombosis 1.01 [0.58; 1.76] definite stent thrombosis 0.62 [0.20; 1.90] | REAL-LATE, ZEST-LATE, 2010 | vs ticlopidine + aspirin | | | all cause death 1.52 [0.76; 3.05] major bleeding 2.97 [0.31; 28.51] stroke 2.23 [0.69; 7.21] MI 1.41 [0.54; 3.70] definite stent thrombosis 1.24 [0.33; 4.60] |
Trial | Treatments | Patients | Method |
---|
Müller, 2000 | Clopidogrel 75 mg qD x4 wks Aspirin 100 mg qD (n=355) vs. Ticlopidine 250 mg BID x4 wks Aspirin 100 mg qD (n=345) | | Sample size: 355/345 Primary endpoint: FU duration: | CLASSICS, 2000 | Clopidogrel 300mg x1, 75 mg qD x4 wks Aspirin 325 mg qDypñ ·` (n=345) vs. Ticlopidine 250 mg BID x4 wks Aspirin 325 mg qD (n=340) | | Sample size: 345/340 Primary endpoint: FU duration: | TOPPS, 2001 | Clopidogrel 300 mg x1, unsp. Dose x2 wks Aspirin 325 mg qD (n=494) vs. Ticlopidine 500 mg x1, unsp. Dose x2 wks Aspirin 325 mg qD (n=522) | | Sample size: 494/522 Primary endpoint: FU duration: | Piamsomboon, 2001 | Clopidogrel 300 mg x1, 75 mg qD x4 wks Aspirin 300 mg BID x4 wks, 300 mg qD (n=37) vs. Ticlopidine 250 mg po BID x4 wks Aspirin 300 mg BID x4 wks, 300 mg qD (n=31) | | Sample size: 37/31 Primary endpoint: FU duration: | GRAVITAS, 2011 | High-dose clopidogrel (600-mg initial dose, 150 mg daily thereafter) (n=1109) vs. regular clopidogrel dose (n=1105) | patients receiving drug-eluting stents with high residual platelet activity (PRU>=230) on the regular clopidogrel dose (platelet-function tests with the VerifyNow assay 12 to 24 hours after PCI) | open Parallel groups Sample size: 1109/1105 Primary endpoint: Cardiovascular death/MI/stent thrombosis FU duration: 6 months | REAL-LATE, ZEST-LATE, 2010 | clopidogrel plus aspirin (n=1357) vs. aspirin alone (n=1344) | patients who had received drugeluting
stents and had been free of major adverse cardiac or cerebrovascular events
and major bleeding for a period of at least 12 months | open Parallel groups Sample size: 1357/1344 Primary endpoint: CV death, MI FU duration: 19.2 months |
|