| acute coronary syndrome | All results are NS for efficacy | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ACUITY (sub groups PCI, bivalirudin alone) importé, 2007 | vs heparin + GP2b3a inhibitors | Major bleeding (non-CABG related) 0,52 [0,40; 0,66] TIMI major bleeding 0,55 [0,44; 0,69] TIMI minor bleeding 0,37 [0,23; 0,60] | | all cause death 1,19 [0,69; 2,06] Myocardial infarction 1,15 [0,93; 1,43] Death, MI, urgent revascularization 1,07 [0,90; 1,28] ischemic event + bleeding 0,87 [0,75; 1,00] | | BAT (Bittl), 1995 | vs heparin + GP2b3a inhibitors | Major bleeding 0,39 [0,30; 0,50] | | Death 2,23 [0,69; 7,22] coronary event 0,89 [0,68; 1,16] long term death 1,62 [0,96; 2,74] MI 0,80 [0,58; 1,11] long term CV event 0,98 [0,88; 1,09] | | ACUITY (biva+aGP2b3a vs hep+aGP2b3a), 2006 | vs heparin + GP2b3a inhibitors | | | all cause death 1,13 [0,80; 1,58] major bleeding 0,94 [0,84; 1,06] MI 1,01 [0,84; 1,21] death, MI, unplanned revascularization 1,07 [0,92; 1,23] major bleeding not related to CABG 0,93 [0,78; 1,10] ischemic events + bleeding 1,01 [0,90; 1,12] major bleeding TIMI 0,88 [0,65; 1,20] 1 yer MI 1,03 [0,89; 1,20] 1 year death from any cause 1,01 [0,82; 1,24] I year Unplanned revascularization for ischemia 1,09 [0,95; 1,24] 1 year composite ischemia 1,04 [0,95; 1,15] | | HERO, 1997 | vs heparin + GP2b3a inhibitors | Major bleeding 0,61 [0,42; 0,89] transfusion 0,51 [0,31; 0,85] | | Death 0,80 [0,36; 1,80] coronary event 0,74 [0,46; 1,18] hemorrhagic stroke +Infini [Non Numérique; +Infini] MI 0,60 [0,29; 1,26] Minor bleeding 1,02 [0,84; 1,23] | | PROTECT-TIMI 30, 2006 | vs heparin + GP2b3a inhibitors | | | | | ACUITY (sub groups PCI, bivalirudin +aGP2b3a) importé, 2007 | vs heparin + GP2b3a inhibitors | | | all cause death 1,28 [0,75; 2,20] Major bleeding (non-CABG related) 1,11 [0,91; 1,35] Myocardial infarction 1,17 [0,94; 1,45] Death, MI, urgent revascularization 1,14 [0,95; 1,36] ischemic event + bleeding 1,12 [0,98; 1,28] TIMI major bleeding 1,07 [0,75; 1,52] TIMI minor bleeding 1,08 [0,90; 1,31] | | ACUITY (biva alone vs hep+aGP2b3a), 2006 | vs heparin + GP2b3a inhibitors | major bleeding 0,77 [0,69; 0,87] major bleeding not related to CABG 0,53 [0,43; 0,65] ischemic events + bleeding 0,86 [0,77; 0,97] major bleeding TIMI 0,50 [0,35; 0,72] | | all cause death 1,19 [0,85; 1,67] MI 1,09 [0,92; 1,30] death, MI, unplanned revascularization 1,08 [0,93; 1,24] 1 yer MI 1,12 [0,97; 1,30] 1 year death from any cause 0,98 [0,80; 1,21] I year Unplanned revascularization for ischemia 1,04 [0,91; 1,20] 1 year composite ischemia 1,05 [0,96; 1,16] |
| Trial | Treatments | Patients | Method |
|---|
| ACUITY (sub groups PCI, bivalirudin alone) importé, 2007 | bivalirudin alone (n=2619) vs. heparin (either unfractionated or enoxaparin) plus glycoprotein IIb/IIIa inhibitors (n=2561) 2×2 factorial design with upstream
glycoprotein IIb/IIIa inhibitor initiation immediately after randomisation versus deferred glycoprotein
IIb/IIIa inhibitor initiation for selective use in the
catheterisation laboratory starting immediately before
percutaneous coronary intervention | patients with moderate and high-risk acute coronary syndromes undergoing percutaneous
coronary intervention after angiography (sub group). | open Factorial plan Sample size: 2619/2561 Primary endpoint: FU duration: 30 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 (n=2059) vs. UFH 175 IU/kg bolus; 15 IU mg /kg/h infusion (n=2039) | patients undergoing angioplasty for unstable or postinfarction angina | double blind Parallel groups Sample size: 2059/2039 Primary endpoint: death, MI, abrupt vessel closure, clinical deterioration FU duration: 6 months | | ACUITY (biva+aGP2b3a vs hep+aGP2b3a), 2006 | bivalirudin plus a glycoprotein IIb/IIIa inhibitor
(n=4604) vs. unfractionated heparin or enoxaparin plus a glycoprotein IIb/IIIa inhibitor
(n=4603) 3 arms: unfractionated heparin or enoxaparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin plus a glycoprotein IIb/IIIa inhibitor, or bivalirudin alone
| in patients with moderate- or high-risk acute coronary syndromes who were undergoing an early invasive strategy.
| double blind Sample size: 4604/4603 Primary endpoint: hierarchical endpoint testing FU duration: 30 days
| | HERO, 1997 | Bivalirudin 0.125–0.250 mg/kg bolus; 0.125–0.500 mg /kg/min infusion for 72h (n=272) vs. UFH 5000 IU bolus; 1000–1200 IU/h infusion (n=140) 3 arms: low-dose, high dose hirulog and heparin | AMI (patients presenting within 12 hours with ST-segment elevation) | double blind Parallel groups Sample size: 272/140 Primary endpoint: TIMI3 of the infarct-related artery at 90 to 120 minutes FU duration: 35 days dose-finding study | | PROTECT-TIMI 30, 2006 | bivalirudin alone (n=284) vs. eptifibatide plus either unfractionated heparin or enoxaparin (n=573) 3 arms trial: eptifibatide reduced dose unfractionated heparin (n=298), eptifibatide reduced-dose enoxaparin (n=275), or bivalirudin monotherapy (n=284) | non ST elevation ACS patients undergoing PCI | open Parallel groups Sample size: 284/573 Primary endpoint: Coronary flow reserve FU duration: hospital stay | | ACUITY (sub groups PCI, bivalirudin +aGP2b3a) importé, 2007 | bivalirudin +
(n=2609) vs. heparin (either unfractionated or
enoxaparin) plus glycoprotein
IIb/IIIa inhibitors
(n=2561) 2×2 factorial design with upstream
glycoprotein IIb/IIIa inhibitor initiation immediately after randomisation versus deferred glycoprotein
IIb/IIIa inhibitor initiation for selective use in the
catheterisation laboratory starting immediately before
percutaneous coronary intervention
| patients with moderate and high-risk acute coronary syndromes undergoing percutaneous
coronary intervention after angiography.
| open Sample size: 2609/2561 Primary endpoint: FU duration: 30 days
| | ACUITY (biva alone vs hep+aGP2b3a), 2006 | bivalirudin alone (n=4612) vs. unfractionated heparin or enoxaparin plus a glycoprotein IIb/IIIa inhibitor (n=4603) 3 arms: unfractionated heparin or enoxaparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin plus a glycoprotein IIb/IIIa inhibitor, or bivalirudin alone | in patients with moderate- or high-risk acute coronary syndromes who were undergoing an early invasive strategy. | double blind Parallel groups Sample size: 4612/4603 Primary endpoint: hierarchical endpoint testing FU duration: 30 days |
|
| percutaneous coronary intervention | All results are NS for efficacy | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ISAR-REACT 3, 2008 | vs UFH | | | | | REPLACE-1, 2004 | vs UFH | | | death, MI, urgent TVR, in-hospital major bleeding 0,77 [0,35; 1,69] All cause death 0,00 [0,00; Non Numérique] MI 0,95 [0,56; 1,60] death, MI, revascularization 0,82 [0,51; 1,31] Unplanned revascularisation for ischaemia 0,56 [0,17; 1,91] | | ACUITY (Stone) (bivalirudin alone), 2006 | vs UFH | | | | | ARMYDA BIVALVE | vs UFH | | | | | BAT (Bittl), 1995 | vs UFH | major bleeding 0,39 [0,30; 0,50] | | All cause death 2,23 [0,69; 7,22] Ischaemic complication 0,93 [0,79; 1,10] MI 0,80 [0,58; 1,11] Unplanned revascularisation for ischaemia 0,99 [0,62; 1,58] | | HORIZONS-AMI (Stone), 2008 | vs UFH | All cause death 0,66 [0,44; 1,00] safety criteria 0,60 [0,46; 0,77] major bleeding 0,61 [0,44; 0,84] minor bleeding 0,62 [0,44; 0,88] net benefit 0,76 [0,63; 0,92] | | Ischaemic complication 0,99 [0,76; 1,30] MI 1,14 [0,64; 2,01] death, MI, revascularization 0,99 [0,76; 1,30] Unplanned revascularisation for ischaemia 1,34 [0,87; 2,07] | | NAPLES (Tavano), 2009 | vs UFH | death, MI, urgent TVR, in-hospital major bleeding 0,57 [0,38; 0,84] minor bleeding 0,42 [0,23; 0,78] | | All cause death Non Numérique [Non Numérique; Non Numérique] major bleeding 0,25 [0,03; 2,23] Unplanned revascularisation for ischaemia Non Numérique [Non Numérique; Non Numérique] | | Kleiman, 2002 | vs UFH | | | | | REPLACE-2, 2003 | vs UFH | | | |
| Trial | Treatments | Patients | Method |
|---|
| ISAR-REACT 3, 2008 | UFH bolus of 140 U/kg (n=2289) vs. bivalirudin (bolus of 0.75 mg/kg, followed by infusion of 1.75 mg/kg/hr) (n=2281) | troponin-negative patients undergoing PCI | double blind Parallel groups Sample size: 2289/2281 Primary endpoint: death, MI, urgent TVR, in-hospital major bleeding, FU duration: 30 days (mean) | | REPLACE-1, 2004 | bivalirudin (0.75 mg/kg bolus, 1.75 mg/kg/h infusion during the procedure (n=532) vs. heparin (70 U/kg initial bolus) adjusted to ACT of 200 to 300s (n=524) | patients undergoing elective or urgent revascularization | Parallel groups Sample size: 532/524 Primary endpoint: death, MI, repeat revascularization FU duration: hospital stay (48h min) | | ACUITY (Stone) (bivalirudin alone), 2006 | bivalirudin alone (n=9216) vs. unfractionated heparin or enoxaparin plus a glycoprotein IIb/IIIa inhibitor (n=4603) | patients with acute coronary syndromes | open Parallel groups Sample size: 9216/4603 Primary endpoint: ischemia events and bleeding FU duration: 30 days | | ARMYDA BIVALVE | bivalirudin (0.75 mg/kg bolus followed by 1.75 mg/kg per hour during the procedure) (n=140) vs. unfractionated heparin (75 IU/kg) (n=0) | patients at high bleeding risk (over 75 years of age, diabetes, reduced renal function) scheduled for PCI | Parallel groups Sample size: 140/0 Primary endpoint: death, MI, target vessel revascularization, or stent thrombosis FU duration: | | BAT (Bittl), 1995 | bivalirudin immediately before angioplasty. (n=2059) vs. heparin immediately before angioplasty (n=2039) | patients undergoing urgent angioplasty for unstable or postinfarction angina | double blind Parallel groups Sample size: 2059/2039 Primary endpoint: death, MI, abrupt clossure, rapide deterioration FU duration: hospital stay Although two parallel studies were
specified to meet regulatory requirements, the protocol specified that scientific analysis and safety monitoring would
involve the combined cohort of 4000 patients | | HORIZONS-AMI (Stone), 2008 | Bivalirudin (n=1800) vs. Heparin plus GP IIb/IIIa inhibitor (n=1802) | patients with ST-segment elevation myocardial infarction
who presented within 12 hours after the onset of symptoms and who were
undergoing primary PCI | open Parallel groups Sample size: 1800/1802 Primary endpoint: MACE, major bleeding FU duration: 30 days | | NAPLES (Tavano), 2009 | bivalirudin monotherapy (n=167) vs. unfractionated heparin plus tirofiban (n=168) | patients with diabetes mellitus undergoing elective percutaneous coronary intervention | open Parallel groups Sample size: 167/168 Primary endpoint: MACE FU duration: 30 days | | Kleiman, 2002 | bivalirudin + eptifibatide (n=-9) vs. heparin + eptifibatide (n=-9) | patients who underwent elective percutaneous coronary intervention | open Parallel groups Sample size: -9/-9 Primary endpoint: none defined FU duration: | | REPLACE-2, 2003 | bivalirudin, with glycoprotein IIb/IIIa (Gp IIb/IIIa) inhibition on a provisional basis for complications during PCI (n=2994) vs. heparin plus planned Gp IIb/IIIa blockade (n=3008) | patients undergoing urgent or elective PCI | double blind Parallel groups Sample size: 2994/3008 Primary endpoint: death, MI, urgent revascularization, or in-hospital FU duration: 30 days |
|
