| pathology | Demonstrated benefit and harm | k | | | |
|---|
| acute coronary syndrome | versus No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ACUITY (biva alone vs hep+aGP2b3a), 2006 | bivalirudin 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] | | ACUITY (biva+aGP2b3a vs hep+aGP2b3a), 2006 | bivalirudin + GP2b3a inhibitors 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] |
| Trial | Treatments | Patients | Method |
|---|
| 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 | | 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
|
|
| acute coronary syndrome | versus eptifibatide + heparin No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| PROTECT-TIMI 30, 2006 | bivalirudin vs eptifibatide + heparin | | | |
| Trial | Treatments | Patients | Method |
|---|
| 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 |
|
| acute coronary syndrome | versus heparin No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| HERO, 1997 | bivalirudin vs heparin | Major bleeding 0.61 [0.42; 0.89] transfusion 0.51 [0.31; 0.85] | | Death 0.80 [0.36; 1.80] MI 0.60 [0.29; 1.26] coronary event 0.74 [0.46; 1.18] Minor bleeding 1.02 [0.84; 1.23] hemorrhagic stroke ∞ [NaN; ∞] | | BAT (Bittl), 1995 | bivalirudin vs heparin | Major bleeding 0.39 [0.30; 0.50] | | Death 2.23 [0.69; 7.22] MI 0.80 [0.58; 1.11] coronary event 0.89 [0.68; 1.16] long term death 1.62 [0.96; 2.74] long term CV event 0.98 [0.88; 1.09] |
| Trial | Treatments | Patients | Method |
|---|
| 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 | | 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 |
|
| acute coronary syndrome | versus heparin+aGP2b3a No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ACUITY (sub groups PCI, bivalirudin +aGP2b3a) importé, 2007 | bivalirudin + GP2b3a inhibitors 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 (sub groups PCI, bivalirudin alone) importé, 2007 | bivalirudin 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] |
| Trial | Treatments | Patients | Method |
|---|
| 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 (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 |
|
| acute myocardial infarction | versus heparin No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| HERO, 1997 | bivalirudin vs heparin | Major bleeding 0.61 [0.42; 0.89] transfusion 0.51 [0.31; 0.85] | | Death 0.80 [0.36; 1.80] MI 0.60 [0.29; 1.26] coronary event 0.74 [0.46; 1.18] Minor bleeding 1.02 [0.84; 1.23] hemorrhagic stroke ∞ [NaN; ∞] |
| Trial | Treatments | Patients | Method |
|---|
| 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 |
|
| percutaneous coronary intervention | versus heparin No demonstrated result for efficacy | 4 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ISAR-REACT 3, 2008 | bivalirudin vs UFH | | | | | REPLACE-1, 2004 | bivalirudin vs UFH | | | death, MI, urgent TVR, in-hospital major bleeding 0.77 [0.35; 1.69] All cause death 0.00 [0.00; NaN] 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] | | BAT (Bittl), 1995 | bivalirudin 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] | | ARMYDA BIVALVE | bivalirudin 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) | | 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 | | 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: |
|
| percutaneous coronary intervention | versus heparin + anti Gp2b3a No demonstrated result for efficacy | 5 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| REPLACE-2, 2003 | bivalirudin vs heparin + GP2b3a inhibitors | | | | | HORIZONS-AMI (Stone), 2008 | bivalirudin vs heparin + GP2b3a inhibitors | 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] | | ACUITY (Stone) (bivalirudin alone), 2006 | bivalirudin vs heparin + GP2b3a inhibitors | | | | | Kleiman, 2002 | bivalirudin + eptifibatide vs heparin + GP2b3a inhibitors | | | | | NAPLES (Tavano), 2009 | bivalirudin vs UFH plus tirofiban | 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 NaN [NaN; NaN] major bleeding 0.25 [0.03; 2.23] Unplanned revascularisation for ischaemia NaN [NaN; NaN] |
| Trial | Treatments | Patients | Method |
|---|
| 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 | | 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 | | 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 | | 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: | | 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 |
|
