| pathology | treatment | patient | Demonstrated benefit and harm | k | | | |
|---|
| acute coronary syndrome | anistreplase | not classified | versus placebo or control No demonstrated result for efficacy anistreplase inferior to placebo in terms of bleeding in UNASEM, 1992 | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| UNASEM, 1992 | anistreplase vs placebo | | bleeding 2.96 [1.34; 6.57] | |
| Trial | Treatments | Patients | Method |
|---|
| UNASEM, 1992 | anistreplase IV 30 UI over 5 minutes (n=80) vs. placebo (n=79) | Patients without a previous myocardial infarction, with a typical history of unstable angina and ECG abnormalities indicative of ischemia | double blind Parallel groups Sample size: 80/79 Primary endpoint: CA FU duration: hospital stay, 1y |
|
| acute coronary syndrome | t-pa | not classified | versus placebo or control No demonstrated result for efficacy t-PA inferior to placebo in terms of bleeding in Williams, 1990 | 10 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Nicklas, 1989 | t-PA vs placebo | | | MI 1.00 [0.16; 6.42] In hospital death ∞ [NaN; ∞] | | Gold, 1987 | t-PA vs placebo | | | | | Williams, 1990 | t-PA vs placebo | | bleeding 2.35 [1.04; 5.32] | MI 1.47 [0.16; 13.30] In hospital death NaN [NaN; NaN] | | Freeman, 1992 | t-PA vs placebo | | | Death 1.00 [0.07; 15.36] MI 2.00 [0.19; 21.06] In hospital death 1.00 [0.07; 15.36] | | van der Brand, 1991 | t-PA vs placebo | | | bleeding ∞ [NaN; ∞] MI 1.19 [0.31; 4.59] | | charbonnier, 1992 | t-PA vs placebo | | | | | Ardissino, 1990 | t-PA vs placebo | | | MI 0.50 [0.05; 4.81] In hospital death 0.00 [0.00; NaN] | | TIMI 3B, 1995 | t-PA vs placebo | | | | | Topol, 1988 | t-PA vs placebo | | | In hospital death ∞ [NaN; ∞] | | TIMI 3A, 1993 | t-PA vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| Nicklas, 1989 | rt-PA, 150 mg/8 h (n=20) vs. placebo (n=20) | patients with rest angina, angiographically documented coronary artery disease and pacing-induced ischemia | Double blind Parallel groups Sample size: 20/20 Primary endpoint: ischemic pacing threshold FU duration: | | Gold, 1987 | intravenous recombinant human tissue-type plasminogen activator (rt-PA). (n=12) vs. placebo (n=12) | chest pain at rest with transient ST segment deviation of at least 1 mm | Parallel groups Sample size: 12/12 Primary endpoint: FU duration: | | 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) (n=45) vs. placebo (n=22) 3 arms study comparing low-dose and high dose of rt-PA to placebo | rest angina and angiographic evidence of coronary stenosis | double blind Parallel groups Sample size: 45/22 Primary endpoint: change in luminal diameter FU duration: | | 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) (n=35) vs. placebo (n=35) | patients with unstable angina | double blind Parallel groups Sample size: 35/35 Primary endpoint: in-hospital death, myocardial infarction, and urgent revascularization FU duration: in hospital | | van der Brand, 1991 | alteplase 100 mg in 3 h (n=19) vs. placebo (n=17) | patients with angina at rest, despite bedrest and medical treatment | double blind Parallel groups Sample size: 19/17 Primary endpoint: FU duration: hospital stay | | charbonnier, 1992 | rt-PA 100 mg/90 minutes (10 mg bolus + 90 mg/90 minutes (n=25) vs. placebo (n=25) | unstable angina pectoris | double blind Parallel groups Sample size: 25/25 Primary endpoint: FU duration: | | Ardissino, 1990 | recombinant tissue-type plasminogen activator (rt-PA) followed by heparin (n=12) vs. heparin alone (n=12) | unstable angina refractory to conventional medical treatment | double blind Parallel groups Sample size: 12/12 Primary endpoint: FU duration: in hospital | | TIMI 3B, 1995 | tissue-type plasminogen activator (t-PA) (n=729) vs. placebo (n=744) factorial design: early invasive management strategy with coronary arteriography at 18 to 48 h, followed by revascularization as soon as possible if appropriate, compared to an early conservative strategy with arteriography and revascularization reserved for failure of initial therapy to prevent recurrent ischemia | patients with unstable angina and non-Q wave myocardial infarction | Double blind Factorial plan Sample size: 729/744 Primary endpoint: death or MI FU duration: 1 year | | Topol, 1988 | intravenous tissue plasminogen activator (t-PA) (n=20) vs. placebo (n=20) | patients with angina at rest and provocable ischemia (pacing induced) | open Parallel groups Sample size: 20/20 Primary endpoint: FU duration: hospital stay | | TIMI 3A, 1993 | 90-minute front-loaded infusion of t-PA (0.8 mg/kg i.v.; maximum, 80 mg) (n=150) vs. placebo (n=156) | patients with unstable angina or non-Q wave myocardial infarction | double blind Parallel groups Sample size: 150/156 Primary endpoint: culprit lesion caliber FU duration: hospital stay |
|
| acute myocardial infarction | anistreplase | not classified | versus other fibrinolytic No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| TEAM 2, 1991 | anistreplase vs streptokinase | | | |
| Trial | Treatments | Patients | Method |
|---|
| TEAM 2, 1991 | anistreplase (30 units/2-5 min) (n=183) vs. streptokinase (1.5 million units/60 min (n=176) | less than 76 years of age with electrocardiographic ST segment elevation who could be treated within 4 hours of symptom onset | double blind Sample size: 183/176 Primary endpoint: FU duration: |
|
| acute myocardial infarction | APSAC | not classified | versus placebo or control No demonstrated result for efficacy | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| AIMS, 1988 | APSAC vs placebo | Mortalité à long terme 0.62 [0.47; 0.82] Mortalité précoce 0.53 [0.37; 0.76] | | Hémorragies majeures précoces 1.02 [0.30; 3.49] AVC précoce 1.02 [0.26; 4.04] | | German Multicenter Trial, 1988 | APSAC vs placebo | Mortalité précoce 0.44 [0.21; 0.95] | | Hémorragies majeures précoces 1.86 [0.65; 5.33] | | APSIM, 1989 | APSAC vs control | | | Mortalité précoce 1.24 [0.43; 3.58] |
| Trial | Treatments | Patients | Method |
|---|
| AIMS, 1988 | APSAC 30U IV in 5 min (n=624) vs. Placebo (n=634) | Hommes et femmes, < 70 ans | double blind Parallel groups Sample size: 624/634 Primary endpoint: 1y death FU duration: 1 y | | German Multicenter Trial, 1988 | APSAC 30 unités en IV en 5 min, puis héparine en IV (17 U/kg/h) 4 h après l'injection d'APSAC (n=162) vs. Héparine 5000 U en bolus en IV, puis 17 U/kg/h (n=151) | Hommes et femmes, < 70 ans | Parallel groups Sample size: 162/151 Primary endpoint: in hospital death FU duration: 28 jours | | APSIM, 1989 | APSAC 30 U over 5 min (n=112) vs. control (conventional heparin therapy, 5,000 IU in a bolus injection) (n=119) | patients with a first acute myocardial infarction within 5 h after the onset of symptoms | open Parallel groups Sample size: 112/119 Primary endpoint: FU duration: 3 weeks |
|
| acute myocardial infarction | APSAC | not classified | versus other fibrinolytic No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ISIS III (SK/APSAC), 1992 | APSAC vs streptokinase | | | Mortalité à long terme 1.02 [0.96; 1.08] Hémorragies majeures précoces 0.85 [0.67; 1.09] Mortalité précoce 1.00 [0.94; 1.08] AVC précoce 0.82 [0.66; 1.02] | | TEAM 3, 1992 | APSAC vs t-PA | | | |
| Trial | Treatments | Patients | Method |
|---|
| ISIS III (SK/APSAC), 1992 | Streptokinase 1.5 MU infused over about 1 h (n=13780) vs. anisoylated plasminogen-streptokinase activator complex (APSAC), anistreplase: 30 U over about 3 min (n=13773) | patients within 24 h of the onset of suspected acute myocardial infarction | double blind Plan factoriel 3 (ou 4) *2 Sample size: 13780/13773 Primary endpoint: Mortality 35-day FU duration: 6 mo | | TEAM 3, 1992 | APSAC, 30 U/2 to 5 min (n=325) vs. rt-PA, 100 mg/3 h, (n=0) | patient with ST elevalation within 4h of the onset of symptoms | double blind Sample size: 325/0 Primary endpoint: FU duration: 1 months |
|
| acute myocardial infarction | lanoteplase | not classified | versus other fibrinolytic No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| InTIME-II, 2000 | lanoteplase vs accelerated t-PA | | | Mortalité à long terme 0.97 [0.88; 1.07] Hémorragies majeures précoces 0.83 [0.53; 1.31] Mortalité précoce 1.02 [0.90; 1.16] AVC précoce 1.22 [0.94; 1.59] |
| Trial | Treatments | Patients | Method |
|---|
| InTIME-II, 2000 | lanoteplase 120 KU. kg(-1) as a single intravenous bolus (n=10038) vs. up to 100 mg accelerated alteplase given over 90 min (n=5022) | patients presenting within 6 h of onset of ST elevation acute myocardial infarction | double blind Parallel groups Sample size: 10038/5022 Primary endpoint: Mortality 30-day FU duration: 30 days |
|
| acute myocardial infarction | reteplase | not classified | versus other fibrinolytic No demonstrated result for efficacy | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| GUSTO III, 1997 | reteplase vs accelerated t-PA | | | Hémorragies majeures précoces 0.79 [0.57; 1.09] Mortalité précoce 1.03 [0.91; 1.17] AVC précoce 0.92 [0.71; 1.18] | | INJECT, 1995 | reteplase vs streptokinase | | | Mortalité précoce 0.95 [0.81; 1.11] AVC précoce 1.23 [0.76; 1.99] | | RAPID-2, 1996 | reteplase vs accelerated t-PA | total patency (TIMI 2 or 3) 1.14 [1.01; 1.28] complete patency (TIMI 3) 1.32 [1.06; 1.65] | | total stroke 0.69 [0.16; 3.02] Hémorragies majeures précoces 1.28 [0.69; 2.40] Haemorraghic stroke 0.61 [0.10; 3.61] Mortalité précoce 0.49 [0.20; 1.21] AVC précoce 0.69 [0.16; 3.02] reinfarction 1.05 [0.39; 2.82] |
| Trial | Treatments | Patients | Method |
|---|
| GUSTO III, 1997 | reteplase, in two bolus doses or 10 MU each given 30 minutes apart (n=10138) vs. alteplase, up to 100 mg infused over a period of 90 minutes (n=4921) | patients within 6 hours after the onset of symptoms with ST-segment elevation or bundle-branch block | open Parallel groups Sample size: 10138/4921 Primary endpoint: Mortality 30-day FU duration: 30 days | | INJECT, 1995 | Reteplase 2 bolus de 10 MU à 30 min d'intervalle (n=3004) vs. Streptokinase 1.5 MU en IV en 60 min (n=3006) | patients with symptoms and electrocardiographic criteria consistent with acute myocardial infarction within 12 h from onset of symptoms | double blind Parallel groups Sample size: 3004/3006 Primary endpoint: Mortality 35-day FU duration: 6 mo | | RAPID-2, 1996 | 10 plus 10 megaunits double bolus of reteplase (n=169) vs. front-loaded alteplase (n=155) | patients with acute myocardial infarction within 12h from onset of ischemic chest pain | open Parallel groups Sample size: 169/155 Primary endpoint: Patency at 90 min FU duration: 35 days |
|
| acute myocardial infarction | saruplase | not classified | versus other fibrinolytic No demonstrated result for efficacy | 4 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| COMPASS, 1998 | saruplase vs streptokinase | | | Mortalité à long terme 0.86 [0.69; 1.08] Hémorragies majeures précoces 0.84 [0.53; 1.34] Mortalité précoce 0.85 [0.64; 1.12] AVC précoce 1.00 [0.56; 1.80] | | PRIMI (vs SK), 1989 | saruplase vs streptokinase | | | | | SESAM, 1997 | saruplase vs t-PA | | | Hémorragies majeures précoces 1.10 [0.62; 1.97] Haemorraghic stroke 1.00 [0.14; 7.07] Mortalité précoce 1.23 [0.52; 2.91] AVC précoce 0.80 [0.22; 2.95] reinfarction 1.00 [0.43; 2.37] | | PRIMI (vs UK), 1989 | saruplase vs urokinase | | | |
| Trial | Treatments | Patients | Method |
|---|
| COMPASS, 1998 | saruplase 20-mg bolus and 60-mg infusion over 60 min (n=1542) vs. streptokinase 1.5-MU infusion over 60 min (n=1547) | patients with symptoms compatible with those of acute myocardial infarction for < 6 h | double blind Parallel groups Sample size: 1542/1547 Primary endpoint: death 30d FU duration: 1 y | | PRIMI (vs SK), 1989 | sarupalse 20 mg bolus followed by 60 mg infusion for 60 min (n=198) vs. 1.5 million IU streptokinase infused over 60 min (n=203) | patients with acute myocardial infarction were within 4 h of onset of symptoms | double blind Parallel groups Sample size: 198/203 Primary endpoint: patency FU duration: ND | | SESAM, 1997 | saruplase 80 mg/hour (n=236) vs. alteplase 100 mg every 3 hours (n=237) | patients with acute myocardial infarction | open Parallel groups Sample size: 236/237 Primary endpoint: patency FU duration: hospital stay | | PRIMI (vs UK), 1989 | 20 mg bolus followed by 60 mg infusion for 60 min (n=198) vs. 80 mg recombinant pro-urokinase (n=-9) | with a first acute myocardial infarction within 4 h of onset of symptoms | double blind Parallel groups Sample size: 198/-9 Primary endpoint: FU duration: |
|
| acute myocardial infarction | streptokinase | not classified | versus placebo or control No demonstrated result for efficacy streptokinase inferior to placebo in terms of Hémorragies majeures précoces in ISAM, 1986 streptokinase inferior to placebo in terms of Hémorragies majeures précoces in ISIS-2 (SK), 1988 streptokinase inferior to placebo in terms of Hémorragies majeures précoces in Western Washington Intravenous Trial, 1988 | 7 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ISAM, 1986 | streptokinase vs placebo | | Hémorragies majeures précoces 4.03 [2.21; 7.35] | Mortalité à long terme 0.98 [0.75; 1.29] Mortalité précoce 0.88 [0.62; 1.25] | | ISIS-2 (SK), 1988 | streptokinase vs placebo | Mortalité précoce 0.77 [0.70; 0.84] | Hémorragies majeures précoces 2.56 [1.48; 4.40] | AVC précoce 0.91 [0.64; 1.29] | | Western Washington Intravenous Trial, 1988 | streptokinase vs placebo | | Hémorragies majeures précoces 23.17 [3.17; 169.20] | Mortalité précoce 0.65 [0.32; 1.33] | | GISSI I, 1986 | streptokinase vs placebo | Mortalité à long terme 0.90 [0.83; 0.97] Mortalité précoce 0.83 [0.75; 0.91] | | | | EMERAS (all delay), 1993 | streptokinase vs placebo | | | Mortalité précoce 0.96 [0.82; 1.13] | | ISIS 2 pilot, 1987 | streptokinase vs placebo | | | | | EMERAS (7-12h), 1993 | streptokinase vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| ISAM, 1986 | 1.5 million IU of streptokinase over 1h (n=859) vs. Placebo (n=882) | patients within six hours after the onset of symptoms of myocardial infarction | double blind Parallel groups Sample size: 859/882 Primary endpoint: Mortality 21-day FU duration: 21 days | | ISIS-2 (SK), 1988 | 1-hour intravenous infusion of 1.5 MU of streptokinase (n=8592) vs. Placebo (n=8595) | patients within 24h of the onset of suspected acute myocardial infarction | double blind plan factoriel 2*2 Sample size: 8592/8595 Primary endpoint: CV Mortality 35-day FU duration: 15 mo | | Western Washington Intravenous Trial, 1988 | Streptokinase en IV, 1.5 M UI en 60 min après injection de benadryl 50 mg en IV et hydrocortisone 100 mg en IV; héparine en IV 1000 UI/h 2h après la streptokinase puis warfarine pendant au moins 3 mois (n=191) vs. Traitement standard, avec ou sans anticoagulant (décidé par le médecin) (n=177) | Hommes et femmes, < ou = 75 ans | Parallel groups Sample size: 191/177 Primary endpoint: death at 14 d FU duration: 1.4 y | | GISSI I, 1986 | Streptokinase 1.5 MU en perfusion IV en 1 heure (n=5860) vs. usual care (n=5852) | patients within 12 h after the onset of symptoms and with no contraindications to SK | open Parallel groups Sample size: 5860/5852 Primary endpoint: in hospital death FU duration: 1 y | | EMERAS (all delay), 1993 | streptokinase 1.5 MU (n=2257) vs. placebo (n=2277) | patients entering hospital up to 24 h after the onset of suspected acute myocardial infarction | double blind Parallel groups Sample size: 2257/2277 Primary endpoint: FU duration: | | ISIS 2 pilot, 1987 | streptokinase 1.5 MU (n=-9) vs. placebo (n=-9) 2nd factor heparin vs placebo | patients with suspected acute myocardial infarction | double blind Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: | | EMERAS (7-12h), 1993 | intravenous streptokinase 1.5 MU (n=2257) vs. placebo (n=2277) | patients presenting 7-12 h from symptom onset | double blind Parallel groups Sample size: 2257/2277 Primary endpoint: in hospital death FU duration: |
|
| acute myocardial infarction | streptokinase | not classified | versus other fibrinolytic No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| GUSTO tPA-SK Hiv, 1993 | t-PA + streptokinase vs streptokinase | | | Mortalité précoce 0.96 [0.88; 1.04] |
| Trial | Treatments | Patients | Method |
|---|
| GUSTO tPA-SK Hiv, 1993 | tPA en IV 1 mg/kg, sans dépasser 90 mg, dont 10 % en bolus + streptokinase 1 MU en 60 min + héparine en IV (5000 U en bolus, 1000 U/h (de préférence 1200 U/h si > 80 kg), poursuivi au moins 48 h) (n=10374) vs. Streptokinase 1.5 MU en 60 min + héparine SC (12500 U 2 fois/j commencée 4h après thrombolytique) combiné à streptokinase (1.5 MU en 60 min) + héparine en IV (5000 U en bolus, puis 1000 U/h (1200 U/h si > 80 kg) poursuivi au moins 48 h) (n=20251) | Hommes et femmes | Parallel groups Sample size: 10374/20251 Primary endpoint: Mortality 30-day FU duration: 30 d |
|
| acute myocardial infarction | t-pa | not classified | versus placebo or control No demonstrated result for efficacy t-PA inferior to placebo in terms of Hémorragies majeures précoces in ASSET, 1988 | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ASSET, 1988 | t-PA vs placebo | Mortalité à long terme 0.79 [0.68; 0.92] Mortalité précoce 0.74 [0.62; 0.89] | Hémorragies majeures précoces 2.89 [1.50; 5.56] | AVC précoce 1.11 [0.65; 1.90] | | LATE, 1993 | t-PA vs placebo | | | Mortalité précoce 0.91 [0.80; 1.03] | | TAMI 6, 1992 | t-PA vs placebo | | | Mortalité à long terme 1.26 [0.57; 2.79] Hémorragies majeures précoces 0.79 [0.18; 3.43] Mortalité précoce 1.05 [0.44; 2.54] reinfarction 0.63 [0.16; 2.57] |
| Trial | Treatments | Patients | Method |
|---|
| ASSET, 1988 | rt-PA 100 mg (n=2516) vs. Placebo (n=2495) | patient with suspected acute myocardial infarction | double blind Parallel groups Sample size: 2516/2495 Primary endpoint: death at 6 mo FU duration: 6 months | | LATE, 1993 | intravenous alteplase (100 mg over 3 h) (n=2836) vs. placebo (n=2875) | patients with symptoms and electrocardiographic criteria consistent with AMI between 6 and 24 h from symptom onset | double blind Parallel groups Sample size: 2836/2875 Primary endpoint: 35-day mortality FU duration: 6 mo | | TAMI 6, 1992 | tissue-type plasminogen activator 100 mg over 2 hours (n=96) vs. placebo (n=101) | patients with 6 to 24 hours of symptoms and ECG ST elevation | double blind Parallel groups Sample size: 96/101 Primary endpoint: FU duration: 6 months |
|
| acute myocardial infarction | t-pa | not classified | versus other fibrinolytic No demonstrated result for efficacy t-PA inferior to streptokinase in terms of total stroke in GISSI II, 1990 t-PA inferior to streptokinase in terms of AVC précoce in International Study Group, 1990 | 16 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| GUSTO tPA Hiv, 1993 | accelerated t-PA vs streptokinase | Mortalité précoce 0.86 [0.79; 0.94] | | | | GISSI II, 1990 | t-PA vs streptokinase | Hémorragies majeures précoces 0.56 [0.37; 0.85] | total stroke 1.41 [1.09; 1.82] | Mortalité précoce 1.04 [0.93; 1.16] AVC précoce 1.30 [0.91; 1.85] | | International Study Group, 1990 | t-PA vs streptokinase | Hémorragies majeures précoces 0.67 [0.49; 0.92] | AVC précoce 1.41 [1.09; 1.83] | Mortalité à long terme 1.05 [0.98; 1.13] Mortalité précoce 1.05 [0.96; 1.15] | | COBALT, 1997 | bolus t-PA vs accelerated t-PA | | | Hémorragies majeures précoces 1.09 [0.61; 1.94] Mortalité précoce 1.06 [0.90; 1.24] AVC précoce 1.25 [0.88; 1.78] | | ISIS III (SK/tPA), 1992 | t-PA vs streptokinase | AVC précoce 0.75 [0.60; 0.93] | | Mortalité à long terme 0.99 [0.94; 1.05] Hémorragies majeures précoces 1.08 [0.83; 1.40] Mortalité précoce 1.02 [0.96; 1.10] | | Centre Illinois, 1993 | t-PA vs streptokinase | | | | | Cherng, 1992 | t-PA vs streptokinase | | | reinfarction 0.46 [0.12; 1.69] | | ECSG, 1985 | t-PA vs streptokinase | | | total stroke 0.00 [0.00; NaN] | | PAIMS, 1989 | t-PA vs streptokinase | | | | | TIMI-1, 1987 | t-PA vs streptokinase | | | | | White, 1989 | t-PA vs streptokinase | | | | | KAMIT, 1991 | t-PA half dose vs t-PA | | | reinfarction 0.00 [0.00; NaN] | | TAMI 5 (t-PA vs uroK), 1991 | t-PA vs urokinase | | | | | TAPS, 1992 | accelerated t-PA vs APSAC | | | Mortalité précoce 0.29 [0.08; 1.15] | | RAAMI, 1992 | accelerated t-PA vs t-PA | | | | | TIMI 4, 1994 | accelerated t-PA vs APSAC | | | |
| Trial | Treatments | Patients | Method |
|---|
| GUSTO tPA Hiv, 1993 | tPA accéléré (15 mg en bolus, puis 0.75 mg/kg en 30 min sans dépasser 50 mg puis 0.5 mg/kg en 60 min sans dépasser 35 mg) + héparine en IV (5000 U en bolus, 1000 U/h (de préférence 1200 U/h si > 80 kg), poursuivi au moins 48 h) (n=10396) vs. Streptokinase 1.5 MU en 60 min + héparine SC (12500 U 2 fois/j commencée 4h après thrombolytique) combiné à streptokinase (1.5 MU en 60 min) + héparine en IV (5000 U en bolus, puis 1000 U/h (1200 U/h si > 80 kg) poursuivi au moins 48 h) (n=20251) | Hommes et femmes | Parallel groups Sample size: 10396/20251 Primary endpoint: Mortality 30-day FU duration: 30 d | | GISSI II, 1990 | alteplase 100 mg infused intravenously over 3 h (n=6182) vs. streptokinase 1.5 MU infused intravenously over 30-60 min (n=6199) | patients with acute myocardial infarction within 6 h from onset of symptoms | open Plan factoriel 2*2 Sample size: 6182/6199 Primary endpoint: Mortality in-hospital FU duration: 6 mo | | International Study Group, 1990 | tPA 100 mg en IV en 3 h (10 mg en bolus, puis 50 mg en 1 h, puis 20 mg/h pendant 2 h) (n=10372) vs. Streptokinase 1.5 MU en IV de 30 à 60 min (n=10396) | patients with suspected acute myocardial infarction of less than 6 h duration | double blind Plan factoriel 2*2 Sample size: 10372/10396 Primary endpoint: in hospital death FU duration: 6 mo | | COBALT, 1997 | of 50 mg of alteplase over a period of 1 to 3 minutes followed 30 minutes later by a second bolus of 50 mg (or 40 mg for patients who weighed less than 60 kg). (n=3585) vs. weight-adjusted, accelerated infusion of 100 mg of alteplase (n=3584) | patients with acute myocardial infarction | double blind Parallel groups Sample size: 3585/3584 Primary endpoint: death 30d FU duration: 30 days | | ISIS III (SK/tPA), 1992 | Streptokinase 1.5 MU en IV d'une heure (n=13780) vs. tPA 0.04 MU/kg en IV en bolus d'1 min, puis 0.36 MU/kg en 1 h, puis 0.067 MU/kg/h pendant 3 h (n=13746) | Hommes et femmes | double blind Plan factoriel 3 (ou 4) *2 Sample size: 13780/13746 Primary endpoint: Mortality 35-day FU duration: 6 mo | | Centre Illinois, 1993 | t-PA 10 mg bolus, followed by 50 mg in the first hour, and 20 mg/hour for the next 2 hours (n=123) vs. SK 375 000 IU bolus, followed by 1 125 000 IU/1 hage/pj (n=130) | patients with AMI within 3h from onset of chest pain | single blind Parallel groups Sample size: 123/130 Primary endpoint: Not stated FU duration: | | Cherng, 1992 | 100 mg of rTPA over 3 hours (with early heparinization) (n=59) vs. 1,500,000 units of streptokinase over 1 hour (n=63) | patients with acute myocardial infarction | open Parallel groups Sample size: 59/63 Primary endpoint: none defined FU duration: hospital stay | | ECSG, 1985 | 0.75 mg rt-PA/kg over 90 min (n=64) vs. 1 500 000 IU streptokinase over 60 min (n=65) | patients with acute myocardial infarction of less than 6 h duration | single-blind Parallel groups Sample size: 64/65 Primary endpoint: Not stated FU duration: | | PAIMS, 1989 | intravenous cumulative dose of 100 mg rt-PA (n=86) vs. .5 million units streptokinase (n=85) | patients with acute myocardial infarction less than 3 h old | open Parallel groups Sample size: 86/85 Primary endpoint: Thrombolytic efficacy and effects on LVF FU duration: | | TIMI-1, 1987 | rt-PA, 40, 20, and 20 mg in successive hours (n=157) vs. SK 1.5 million units over 1 hr (n=159) | patients with evolving acute myocardial infarction within 7 hr of the onset of symptoms | double blind Parallel groups Sample size: 157/159 Primary endpoint: Patency at 90 min FU duration: | | White, 1989 | rt-PA 100 mg over three hours (n=135) vs. streptokinase 1.5 million units over 30 minutes (n=135) | patients with AMI | double blind Parallel groups Sample size: 135/135 Primary endpoint: LVF FU duration: | | KAMIT, 1991 | half-dose (50 mg) t-PA with streptokinase (1.5 MU) during 1 hour (n=109) vs. t-PA (100 mg) during 3 hours (n=107) | patients within 6 hours of myocardial infarction | open Parallel groups Sample size: 109/107 Primary endpoint: Patency at 90 min FU duration: hospital stay | | TAMI 5 (t-PA vs uroK), 1991 | accelerated t-PA 100mg over 3h (n=191) vs. urokinase IV bolus 1.5 MU followed by 1.5 MU over 90min (n=190) | patient with acute myocardial infarction | open Sample size: 191/190 Primary endpoint: FU duration: | | TAPS, 1992 | front-loaded administration of rt-PA (n=199) vs. APSAC (n=202) | patients with acute myocardial infarction. | open Parallel groups Sample size: 199/202 Primary endpoint: FU duration: | | RAAMI, 1992 | 100 mg of rt-PA accelerated 90-min regimen (15-mg bolus followed by 50 mg over 30 min, then 35 mg over 60 min) (n=143) vs. 100 mg of rt-PA standard 3-h infusion regimen (an initial 10-mg bolus followed by 50 mg for the 1st h, then 20 mg/h for 2 h (n=138) | patients with acute myocardial infarction within 6h from onset of chest pain | open Parallel groups Sample size: 143/138 Primary endpoint: patency 90 min FU duration: hospital stay | | TIMI 4, 1994 | front-loaded rt-PA (n=-9) vs. APSAC (n=-9) | patients with acute myocardial infarction | double blind Sample size: -9/-9 Primary endpoint: unsatisfactory outcome FU duration: hospital stay |
|
| acute myocardial infarction | tenecteplase | not classified | versus other fibrinolytic No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ASSENT-2, 1999 | tenecteplase vs accelerated t-PA | Hémorragies majeures précoces 0.78 [0.69; 0.89] | | Mortalité précoce 1.01 [0.89; 1.13] AVC précoce 1.07 [0.86; 1.35] |
| Trial | Treatments | Patients | Method |
|---|
| ASSENT-2, 1999 | Tenecteplase en IV bolus (dose en fonction du poids: 30 mg si < 60 kg; 35 mg si poids entre 60 et 69.9 kg; 40 mg pour les 80-89.9 kg; 50 mg si > ou = 90 kg (n=8461) vs. Alteplase en IV, bolus de 15 mg, puis 0.75 mg/kg (sans dépasser 50 mg) en 30 min puis 0.50 mg/kg (sans dépasser 35 mg) en 60 min (n=8488) | patients with acute myocardial infarction of less than 6 h duration | double blind Parallel groups Sample size: 8461/8488 Primary endpoint: Mortality 30-day FU duration: 30d |
|
| acute myocardial infarction | urokinase | not classified | versus placebo or control No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| USIM, 1991 | urokinase vs control | | | |
| Trial | Treatments | Patients | Method |
|---|
| USIM, 1991 | urokinase bolus dose of 1 million U repeated after 60 minutes plus heparin (n=1128) vs. control (heparin alone) (n=1073) | patients with acute myocardial infarction within 4 hours of the onset of pain | open Parallel groups Sample size: 1128/1073 Primary endpoint: FU duration: in hospital |
|
| cardiac arrest | t-pa | not classified | versus placebo No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Abu-Laban, 2002 | t-PA vs placebo | | | death 0.99 [0.97; 1.01] Survival to hospital discharge ∞ [NaN; ∞] Return of spontaneous circulation 0.92 [0.57; 1.48] failure to return of spontaneous circulation 1.02 [0.89; 1.18] death before hospital discharge 0.99 [0.97; 1.01] |
| Trial | Treatments | Patients | Method |
|---|
| Abu-Laban, 2002 | t-PA 100mg over a 15-minute period (n=117) vs. placebo (n=116) | Victims of cardiac arrest with pulseless electrical activity for more than one minute and had had no palpable pulse for more than three minutes during resuscitative efforts and at the time of the initiation of the study drug | double blind Parallel groups Sample size: 117/116 Primary endpoint: survival to hospital FU duration: |
|
| cardiac arrest | tenecteplase | not classified | versus placebo No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| TROICA, 2008 | tenecteplase vs placebo | | | death 0.87 [0.66; 1.14] Ischemic stroke 0.87 [0.66; 1.14] Symptomatic intracranial hemorrhage 0.87 [0.66; 1.14] Survival to hospital discharge 0.87 [0.66; 1.14] Return of spontaneous circulation 0.87 [0.66; 1.14] failure to return of spontaneous circulation 1.03 [0.97; 1.08] death before hospital discharge 1.03 [0.97; 1.08] | | TICA, 2004 | tenecteplase vs placebo | | | death 0.95 [0.78; 1.17] |
| Trial | Treatments | Patients | Method |
|---|
| TROICA, 2008 | tenecteplase (dose according to estimated
body weight) (n=525) vs. placebo (n=525) | adults with witnessed out-of-hospital cardiac arrest of presumed cardiac origin and with initiation of basic or advanced life support within 10 minutes after collapse | doubel blind Parallel groups Sample size: 525/525 Primary endpoint: 30-day survival FU duration: 30 days | | TICA, 2004 | tenecteplase 50 mg (n=19) vs. placebo (n=16) | All victims of out of hospital cardiac arrest | double blind Parallel groups Sample size: 19/16 Primary endpoint: return of spontaneous circulation FU duration: |
|
| pulmonary embolism | candesartan | not classified | versus No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Tebbe, 2009 | desmoteplase vs alteplase | | | |
| Trial | Treatments | Patients | Method |
|---|
| Tebbe, 2009 | 125, 180, and 250 microg/kg bodyweight desmoteplase (n=34) vs. 100 mg alteplase (n=0) | acute massive pulmonary thromboembolism | NA Parallel groups Sample size: 34/0 Primary endpoint: FU duration: |
|
| pulmonary embolism | rt-PA | not classified | versus No demonstrated result for efficacy rt-PA inferior to placebo in terms of minor bleeding in Levine, 1990 | 5 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| PIOPED, 1990 | rt-PA vs placebo | | | All cause death ∞ [NaN; ∞] major bleeding ∞ [NaN; ∞] | | Levine, 1990 | rt-PA vs placebo | | minor bleeding 11.36 [1.61; 80.39] | All cause death ∞ [NaN; ∞] major bleeding NaN [NaN; NaN] recurrence of pulmonary embolism NaN [NaN; NaN] | | PAIMS 2, 1992 | rt-PA vs no fibrinolysis | | | All cause death 1.60 [0.16; 16.10] major bleeding 1.20 [0.23; 6.34] minor bleeding 2.20 [0.86; 5.61] recurrence of pulmonary embolism 0.40 [0.04; 4.02] | | Goldhaber, 1993 | rt-PA vs no fibrinolysis | | | All cause death 0.00 [0.00; NaN] major bleeding 3.59 [0.39; 33.33] recurrence of pulmonary embolism 0.00 [0.00; NaN] | | Konstantinides, 2002 | rt-PA vs placebo | | | All cause death 1.56 [0.36; 6.83] major bleeding 0.23 [0.03; 1.97] recurrence of pulmonary embolism 1.17 [0.30; 4.57] |
| Trial | Treatments | Patients | Method |
|---|
| PIOPED, 1990 | rt-PA 40–80 mg IV over 90 min plus heparin (n=9) vs. placebo+heparin (n=4) | patients with acute pulmonary embolism | double blind Parallel groups Sample size: 9/4 Primary endpoint: FU duration: 7 days | | Levine, 1990 | rt-PA 0.6 mg/kg IV over 2 min and heparin, initial bolus of 5000 U, then 30,000 U for first 24 hr continuous infusion,only interrupted for the duration of the study drug infusion (n=33) vs. placebo + heparin bolus of 5000 U, then 30,000 U for first 24 hr continuous infusion (n=25) | patients with objectively established acute symptomatic pulmonary embolism | double blind Parallel groups Sample size: 33/25 Primary endpoint: FU duration: 10 days | | PAIMS 2, 1992 | rt-PA 100 mg IV over 2 h and heparin (n=-9) vs. Heparin 1750 IU/hr i.v. for 7 to 10 days (n=-9) | patients with angiographically documented pulmonary embolism | open Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: 7 days | | Goldhaber, 1993 | rt-PA 100 mg IV over 2 h then 1000 U/hr heparin,when PTT or TT was < 2 times control. Subsequent heparin dose achieved PTT = 1.5 to 2.5 times the upperlimit of normal. (n=46) vs. heparin, initial dose 5000 U bolus followed by 1000 U/hr continuous i.v., 4 hr after the dose of heparin according to PTT. Target PTT = 1.5 to 2.5 times of normal (n=55) | haemodynamically stable patients with acute pulmonary embolism | open Parallel groups Sample size: 46/55 Primary endpoint: Right-ventricular wall motion FU duration: 14 days | | Konstantinides, 2002 | 100 mg alteplase given as 10 mg bolus followed by 90 mg i.v. infusion over 2 hours then i.v. heparin 1000 U/hr adjusted to maintain APTT of 2.0 to 2.5times the upper normal limit. Oral anticoagulation was started on day 3 (n=118) vs. placebo + i.v. heparin 1000 U/hr adjusted to maintain APTT of 2.0 to 2.5times the upper normal limit. Oral anticoagulation was started on day 3 (n=138) | patients with acute pulmonary embolism and pulmonary hypertensionor right ventricular dysfunction but withoutarterial hypotension or shock | double blind Parallel groups Sample size: 118/138 Primary endpoint: in-hospital death or clinical deterioration FU duration: <30 days |
|
| pulmonary embolism | streptokinase | not classified | versus No demonstrated result for efficacy | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Tibbutt, 1974 | streptokinase vs no fibrinolysis | | | All cause death 0.00 [0.00; NaN] major bleeding 1.31 [0.09; 19.00] minor bleeding 0.33 [0.04; 2.59] | | Ly, 1978 | streptokinase vs no fibrinolysis | | | All cause death 0.39 [0.04; 3.79] major bleeding 1.57 [0.35; 7.06] minor bleeding 0.98 [0.34; 2.81] | | Jerjes-Sanchez, 1995 | streptokinase vs no fibrinolysis | | | |
| Trial | Treatments | Patients | Method |
|---|
| Tibbutt, 1974 | intrapulmonary SK 600,000-U bolus, then 100,000 U/h for 72 h and intrapulmonary heparin (n=17) vs. 5000U heparin plus 100mg hydrocortisone infused over 30 mins through pulmonary artery catheter. Followed by 2500 U for 72 hr (n=13) | life-threatening pulmonary embolism | open Parallel groups Sample size: 17/13 Primary endpoint: FU duration: 3 days | | Ly, 1978 | streptokinase 250,000-U bolus, then 100,000 U/h for 72 h and heparin (n=14) vs. Heparin 15,000 IU initial dose i.v. followed by 30,000 IU/day continuous i.v., adjusted by TT (n=11) | patients with major pulmonary embolism verified by angiography | open Parallel groups Sample size: 14/11 Primary endpoint: FU duration: 10 days | | Jerjes-Sanchez, 1995 | streptokinase 1,500,000 U IV over 1 h and heparin (n=43) vs. heparin alone (n=5) | high clinical suspicion for massive pulmonary embolism | open Parallel groups Sample size: 43/5 Primary endpoint: FU duration: 3 days |
|
| pulmonary embolism | urokinase | not classified | versus No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| UPET, 1973 | urokinase vs placebo | | | All cause death 0.82 [0.29; 2.32] major bleeding 1.90 [0.99; 3.66] minor bleeding 1.43 [0.68; 2.98] recurrence of pulmonary embolism 0.76 [0.38; 1.52] | | Marini, 1988 | urokinase vs no fibrinolysis | | | |
| Trial | Treatments | Patients | Method |
|---|
| UPET, 1973 | urokinase 2,000-U/lb bolus, then 2,000 U/lb per h IV for 12 h and heparin (n=82) vs. placebo + Heparin (a loading dose of 75 U/pound, then 10 U/pound/hr for 12 hr infusion, then heparin for a minimum of 5 days, followed by heparin or warfarin therapy for a total of 14 days) (n=78) | patients with pulmonary embolism | double blind Parallel groups Sample size: 82/78 Primary endpoint: FU duration: <14 days | | Marini, 1988 | urokinase 800,000 U/d IV for 72 h, UK 3,300,000 U IV for 12 h and heparin (n=20) vs. heparin (n=10) | patients with pulmonary embolism | open Sample size: 20/10 Primary endpoint: FU duration: 7 days |
|
| venous thrombosis | heparin | not classified | versus No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Schweizer tPA, 1998 | tPA+heparin vs no fibrinolysis | | | Bleeding (early) ∞ [NaN; ∞] Complete clot lysis (late) 1.25 [0.61; 2.56] Post-thrombotic syndrome (late) 0.82 [0.56; 1.21] Leg ulceration (late) 2.00 [0.20; 20.49] Stroke/intracerebral bleeding (eraly) NaN [NaN; NaN] |
| Trial | Treatments | Patients | Method |
|---|
| Schweizer tPA, 1998 | tPA 20 mg IV into pedal vein over 4 hours each day for 7 days. Heparin IV given
concomitantly, with adjustment (n=-9) vs. heparin IV, adjusted for 7 days (n=-9) | patients with venographically confirmed DVT of leg duration < 7 days. | single blind Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: |
|
| venous thrombosis | streptokinase | not classified | versus No demonstrated result for efficacy streptokinase inferior to no fibrinolysis in terms of Any improvement in venous patency (early) in Arneson, 1978 streptokinase inferior to no fibrinolysis in terms of Normal venous function (late) in Elsharawy, 2002 streptokinase inferior to no fibrinolysis in terms of Complete clot lysis (late) in Elsharawy, 2002 | 7 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Arneson, 1978 | streptokinase vs no fibrinolysis | | Any improvement in venous patency (early) 3.00 [1.33; 6.75] | Mortality (early) 0.00 [0.00; NaN] Pulmonary embolism (early) 1.00 [0.07; 14.96] Bleeding (early) 1.00 [0.29; 3.48] Complete clot lysis (late) ∞ [NaN; ∞] Post-thrombotic syndrome (late) 0.47 [0.18; 1.25] Mortality (late) 1.33 [0.34; 5.24] Leg ulceration (late) 0.00 [0.00; NaN] Stroke/intracerebral bleeding (eraly) NaN [NaN; NaN] | | Common, 1976 | streptokinase vs no fibrinolysis | | | Complete clot lysis (early) 6.78 [0.88; 52.23] Mortality (early) ∞ [NaN; ∞] Bleeding (early) 1.58 [0.58; 4.31] Any improvement in venous patency (early) 1.35 [0.92; 1.98] Complete clot lysis (late) 4.80 [0.67; 34.64] Stroke/intracerebral bleeding (eraly) ∞ [NaN; ∞] | | Elsharawy, 2002 | streptokinase vs no fibrinolysis | | Normal venous function (late) 6.14 [1.62; 23.28] Complete clot lysis (late) 6.14 [1.62; 23.28] | Complete clot lysis (early) ∞ [NaN; ∞] Mortality (early) NaN [NaN; NaN] Pulmonary embolism (early) 0.00 [0.00; NaN] Bleeding (early) NaN [NaN; NaN] Any improvement in venous patency (early) ∞ [NaN; ∞] Stroke/intracerebral bleeding (eraly) NaN [NaN; NaN] | | Schulman, 1986 | streptokinase vs no fibrinolysis | | | Complete clot lysis (early) 1.24 [0.59; 2.60] Mortality (early) 1.12 [0.08; 16.52] Pulmonary embolism (early) NaN [NaN; NaN] Bleeding (early) 3.35 [0.38; 29.27] Normal venous function (late) 1.04 [0.59; 1.83] Complete clot lysis (late) 1.47 [0.77; 2.79] Leg ulceration (late) NaN [NaN; NaN] Stroke/intracerebral bleeding (eraly) NaN [NaN; NaN] | | Tsapogas, 1973 | streptokinase vs no fibrinolysis | | | Stroke/intracerebral bleeding (eraly) NaN [NaN; NaN] | | Kakkar (streptokinase), 1969 | streptokinase vs no fibrinolysis | | | Complete clot lysis (early) 3.00 [0.81; 11.08] Mortality (early) 1.00 [0.17; 5.77] Pulmonary embolism (early) 0.00 [0.00; NaN] Bleeding (early) 1.80 [0.43; 7.59] Any improvement in venous patency (early) 1.75 [0.78; 3.93] Stroke/intracerebral bleeding (eraly) NaN [NaN; NaN] | | Schweizer (systemic SK), 2000 | streptokinase vs no fibrinolysis | | | |
| Trial | Treatments | Patients | Method |
|---|
| Arneson, 1978 | streptokinase 250,000 U loading IV, then 100,000 IU/hour IV 72-96 hours
(n=43) vs. heparin 15,000 IU IV bolus, 30,000 IU infusion IV 72-90 hours¢ßl (n=0) | inpatients with venographically confirmed DVT extending proximally beyond the calf <5 days duration? | single blind Parallel groups Sample size: 43/0 Primary endpoint: FU duration: | | Common, 1976 | hydrocortisone 100 mg IV then streptokinase IV 250,000 U over 30 minutes, then 100,000
U/hour titrated for 72 hours. Followed by IV heparin titrated over 7 days (n=50) vs. IV heparin 150 U/kg loading dose then titrated for 10 days (n=0) | patients with venographically confirmed DVT duration < 14 days | single blind Parallel groups Sample size: 50/0 Primary endpoint: FU duration: | | Elsharawy, 2002 | catheter-directed thrombolysis with streptokinase using popliteal approach. (n=35) vs. heparin IV bolus 5000 U, then adjusted continuous infusion. Warfarin begun the same evening (n=0) | iliofemoral venous thrombosis confirmed by duplex or venography duration < 10 daysicatio | single blind Parallel groups Sample size: 35/0 Primary endpoint: FU duration: | | Schulman, 1986 | streptokinase 50,000 IU IV over 15 minutes then 100,000 IU over 12 hours for up to 7 days,
titrated. Given with 5000 IU heparin IV over 12 hours. Warfarin begun after streptokinase ended (n=38) vs. heparin 5000 IUIVbolus then 30,000 IUper day, titrated for 7 days.Warfarin begun simultaneously (n=0) | patients with venographically confirmed calf vein thrombosis of duration < 7 days. | single blind Parallel groups Sample size: 38/0 Primary endpoint: FU duration: | | Tsapogas, 1973 | titrated dose of streptokinase IV into ankle veinmage/pj (n=34) vs. heparin IV into affected limbitm (n=0) | patients with DVT confirmed by venogram of duration < 5 days. | open Parallel groups Sample size: 34/0 Primary endpoint: FU duration: | | Kakkar (streptokinase), 1969 | streptokinase 500,000 U IV over 30 minutes, 900,000 U every 6 hours for 5 days (n=-9) vs. heparin 10,000 U over 5 minutes, then 10,000 to 15,000 U every 6 hours for 5 dayslicatio (n=-9) | patients with venographically confirmed DVT of leg of duration < 4 days | single blind Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: | | Schweizer (systemic SK), 2000 | Systemic streptokinase 3,000,000 U/day over 6 hours in conjunction with heparin for up to 7 days. Premedication: hydrocortisone 100 mg, ranitidine 50 mg, clemastine 2 mg (n=-9) vs. heparin IV, adjusted (n=-9) | patients with thrombosis of popliteal or more proximal veins confirmed by venogram at more than one level of duration < 9 days | single blind Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: |
|
| venous thrombosis | t-pa | not classified | versus No demonstrated result for efficacy tPA inferior to no fibrinolysis in terms of Any improvement in venous patency (early) in Turpie, 1990 | 6 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Goldhaber (tPA alone), 1990 | tPA vs no fibrinolysis | | | Bleeding (early) ∞ [NaN; ∞] Any improvement in venous patency (early) 3.28 [0.90; 11.91] | | Schweizer (local tPA), 2000 | tPA vs no fibrinolysis | | | | | Turpie, 1990 | tPA vs no fibrinolysis | | Any improvement in venous patency (early) 2.57 [1.35; 4.88] | Bleeding (early) 2.56 [0.53; 12.46] Stroke/intracerebral bleeding (eraly) NaN [NaN; NaN] | | Verhaeghe (high dose), 1989 | tPA vs no fibrinolysis | | | | | Goldhaber (tPA+heparin), 1990 | tPA vs no fibrinolysis | | | | | Verhaeghe (low dose), 1989 | tPA vs no fibrinolysis | | | |
| Trial | Treatments | Patients | Method |
|---|
| Goldhaber (tPA alone), 1990 | tPA alone 0.05 mg/kg/hour IV over 24 hours, then heparin100U/kg bolus, then 1000 U/hour, adjusted (n=-9) vs. heparin alone 100 U/kg bolus, then 1000 U/hour (n=-9) | venographically documented DVT, in popliteal ormore proximal veins < 14 days duration | single blind Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: | | Schweizer (local tPA), 2000 | local tPA 20 mg/day, over 4 hours via pedal vein for 4-7 days. IV heparin given
simultaneously at 1000 IU/hour, adjusted (n=-9) vs. heparin IV, adjusted (n=-9) | patients with thrombosis of popliteal or more proximal veins confirmed by venogram at more than one level of duration < 9 days | single blind Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: | | Turpie, 1990 | tPA + IV heparin (n=83) vs. 5000 U bolus then 30,000 U/24 hours, adjusted for 7-10 days (+placebo) (n=0) | patients with venographically confirmed proximal DVT of lower limb of duration < 7 days | double blind Parallel groups Sample size: 83/0 Primary endpoint: FU duration: | | Verhaeghe (high dose), 1989 | IV tPA 100 mg on day 1, 50 mg tPA on day 2. 10% of dose given as bolus; heparin 5000 U IV bolus then continuous infusion of 1000 U per hour for up to 72 hours (n=-9) vs. heparin 5000 U IV bolus then continuous infusion of 1000 U per hour for up to 72 hours (+placebo) (n=-9) | hospitalised patients with DVT of popliteal or more proximal veins of the lower leg, confirmed by venography of duration < 10 days. | double blind Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: | | Goldhaber (tPA+heparin), 1990 | tPA 0.05 mg/kg/hour IV over 24 hours and heparin 100U/kg bolus, then 1000 U/hour, adjusted (n=-9) vs. heparin alone 100 U/kg bolus, then 1000 U/hour. (n=-9) | patients with venographically documented DVT, in popliteal ormore proximal veins < 14 days duration | single blind Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: | | Verhaeghe (low dose), 1989 | IV tPA 50 mg on day 1, repeated on day 2. 10% of dose given as bolus; heparin 5000 U IV bolus then continuous infusion of 1000 U per hour for up to 72 hours (n=-9) vs. heparin 5000 U IV bolus then continuous infusion of 1000 U per hour for up to 72 hours (+placebo) (n=-9) | hospitalised patients with DVT of popliteal or more proximal veins of the lower leg, confirmed by venography of duration < 10 days. | double blind Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: |
|
| venous thrombosis | urokinase | not classified | versus No demonstrated result for efficacy urokinase inferior to no fibrinolysis in terms of Complete clot lysis (late) in Schweizer (urokinase), 1998 | 4 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Kiil, 1981 | urokinase vs no fibrinolysis | | | Mortality (early) 0.00 [0.00; NaN] Bleeding (early) 0.61 [0.18; 2.06] Any improvement in venous patency (early) 0.73 [0.05; 9.97] Stroke/intracerebral bleeding (eraly) NaN [NaN; NaN] | | Schweizer (urokinase), 1998 | urokinase vs no fibrinolysis | | Complete clot lysis (late) 2.13 [1.17; 3.86] | Mortality (early) ∞ [NaN; ∞] Post-thrombotic syndrome (late) 0.65 [0.40; 1.04] Leg ulceration (late) 1.00 [0.07; 15.00] Stroke/intracerebral bleeding (eraly) NaN [NaN; NaN] | | Schweizer (local urokinase), 2000 | urokinase vs no fibrinolysis | | | | | Schweizer (systemic urokinase), 2000 | urokinase vs no fibrinolysis | | | |
| Trial | Treatments | Patients | Method |
|---|
| Kiil, 1981 | urokinase 200,000 U IV over 24 hours. After 18 hours, heparin loading dose of 15,000 units
then 40,000 U/day for 5 days (+placebo) (n=20) vs. heparin 40,000 U/day IV for 6 days (+placebo) (n=0) | patients with venographically confirmed DVT duration < 72 hours | Double blind Parallel groups Sample size: 20/0 Primary endpoint: FU duration: | | Schweizer (urokinase), 1998 | Urokinase 100,000 IU/hr IV into pedal vein continuously for 7 days. Heparin IV for 7 days. Plasminogen
monitored. Warfarin from day 7 to 12 monthsd=132 (n=-9) vs. heparin IV, adjusted for 7 days (n=-9) | patients with venographically confirmed DVT of leg duration < 7 days | single blind Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: | | Schweizer (local urokinase), 2000 | Local urokinase 100,000 IU/day infused continuously. Fibrinogen and plasminogen monitored. Heparin IV given concomitantly (n=-9) vs. heparin IV, adjusted (n=-9) | patients with thrombosis of popliteal or more proximal veins confirmed by venogram at more than one level of duration < 9 days | single blind Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: | | Schweizer (systemic urokinase), 2000 | Systemic urokinase 5,000,000 IU/day over 4 hours for up to 7 days. IV heparin given concomitantly (n=-9) vs. heparin IV, adjusted (n=-9) | patients with thrombosis of popliteal or more proximal veins confirmed by venogram at more than one level of duration < 9 days | single blind Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: |
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