Phase 3 trials of new anticoagulant for acute coronary syndrome and percutaneous coronary intervention
. | . | . | . | . | . | . | Results . | . | |
|---|---|---|---|---|---|---|---|---|---|
| Drug . | Study . | No. of patients . | Population . | Regimen . | Control . | Outcome measure . | Outcome measure . | Major bleeding . | |
| Hirudin | OASIS-262 | 10 141 | ACS non-ST | 0.4 mg/kg bolus and infusion 0.15 mg/kg/hr × 72 h | IV UFH × 72 h | Cardiovascular death, MI, or refractory angina at d 7 | Hirudin: 284/5083 (5.6%) | Hirudin: 59/5083 (1.2%) | |
| UFH: 340/5058 (6.7%) | UFH: 34/5058 (0.7%) | ||||||||
| P = .01 | P = .01 | ||||||||
| TIMI-9B69 | 3002 | STEMI-all received thrombolysis | 0.1 mg/kg bolus and infusion 0.1 mg/kg/h × 96 h | IV UFH × 96 h | Death, recurrent nonfatal MI, severe CCF, or cardiogenic shock at 30 d | Hirudin: 195/1511 (12.9%) | Hirudin: 68/1474 (4.6%) | ||
| UFH: 178/1491 (11.9%) | UFH: 77/1456 (5.3%) | ||||||||
| NS | NS | ||||||||
| GUSTO-2B69 | 12 142 | ACS* | 0.1 mg/kg bolus and infusion 0.1 mg/kg/h × 72 h IV infusion | IV UFH × 72 h | Death and nonfatal MI at 30 d | Hirudin: 8.9%* | Hirudin: 1.2%* | ||
| UFH: 9.8% | UFH: 1.1%† | ||||||||
| NS | NS | ||||||||
| HELVETICA70 | 1141 | PCI after ACS non-ST | IV bolus 40 mg then IV infusion 0.1 mg/kg/h × 24 h then either hirudin 40 mg SC bid or placebo × 3 d | IV UFH × 24 h then placebo × 3 d | Event-free survival at 7 mo | Hir IV: 242/381 (64%) | Hir IV: 18/381 (4.7%) | ||
| Hir IV/SC: 257/378 (68%) | Hir IV/SC: 28/378 (7.4%) | ||||||||
| UFH IV: 257/382 (67%) | UFH IV: 24/382 (6.2%) | ||||||||
| NS | NS | ||||||||
| Bivalirudin | Bittl et al74 | 4098 | PCA for unstable or postinfarct angina | IV bolus (1 mg/kg) then IV infusion × 24 h | IV UFH × 24 h | Death, MI, abrupt vessel closure, and cardiac clinical deterioration in-hospital | Biv: 235/2059 (11.4%) | Biv: 82/2161 (3.8%) | |
| UFH: 249/2039 (12.2%) | UFH: 210/2151 (9.8%) | ||||||||
| NS | P = .001 | ||||||||
| REPLACE-275 | 6010 | PCI | IV 0.75 mg/kg bolus then infusion 1.75 mg/kg/h +/- GPIIbIIIa inh‡ | IV UFH + GPIIbIIIa inh‡ | Death, MI, urgent revascularization or major bleeding at 30 d | Biv: 275/2975 (9.2%) | Biv: 71/2993 (2.4%) | ||
| UFH: 299/2991 (10%) | UFH: 123/3008 (4.1%) | ||||||||
| NS | P = .001 | ||||||||
| HERO-276 | 17 073 | STEMI-all received thrombolysis | IV 0.25 mg/kg bolus then infusion × 48 h | IV UFH × 48 h | Death at 30 d | Biv: 919/8516 (10.8%) | Biv: 58/8516 (0.7%) | ||
| UFH: 931/8557 (10.9%) | UFH: 40/8557 (0.5%)† | ||||||||
| NS | NS | ||||||||
. | . | . | . | . | . | . | Results . | . | |
|---|---|---|---|---|---|---|---|---|---|
| Drug . | Study . | No. of patients . | Population . | Regimen . | Control . | Outcome measure . | Outcome measure . | Major bleeding . | |
| Hirudin | OASIS-262 | 10 141 | ACS non-ST | 0.4 mg/kg bolus and infusion 0.15 mg/kg/hr × 72 h | IV UFH × 72 h | Cardiovascular death, MI, or refractory angina at d 7 | Hirudin: 284/5083 (5.6%) | Hirudin: 59/5083 (1.2%) | |
| UFH: 340/5058 (6.7%) | UFH: 34/5058 (0.7%) | ||||||||
| P = .01 | P = .01 | ||||||||
| TIMI-9B69 | 3002 | STEMI-all received thrombolysis | 0.1 mg/kg bolus and infusion 0.1 mg/kg/h × 96 h | IV UFH × 96 h | Death, recurrent nonfatal MI, severe CCF, or cardiogenic shock at 30 d | Hirudin: 195/1511 (12.9%) | Hirudin: 68/1474 (4.6%) | ||
| UFH: 178/1491 (11.9%) | UFH: 77/1456 (5.3%) | ||||||||
| NS | NS | ||||||||
| GUSTO-2B69 | 12 142 | ACS* | 0.1 mg/kg bolus and infusion 0.1 mg/kg/h × 72 h IV infusion | IV UFH × 72 h | Death and nonfatal MI at 30 d | Hirudin: 8.9%* | Hirudin: 1.2%* | ||
| UFH: 9.8% | UFH: 1.1%† | ||||||||
| NS | NS | ||||||||
| HELVETICA70 | 1141 | PCI after ACS non-ST | IV bolus 40 mg then IV infusion 0.1 mg/kg/h × 24 h then either hirudin 40 mg SC bid or placebo × 3 d | IV UFH × 24 h then placebo × 3 d | Event-free survival at 7 mo | Hir IV: 242/381 (64%) | Hir IV: 18/381 (4.7%) | ||
| Hir IV/SC: 257/378 (68%) | Hir IV/SC: 28/378 (7.4%) | ||||||||
| UFH IV: 257/382 (67%) | UFH IV: 24/382 (6.2%) | ||||||||
| NS | NS | ||||||||
| Bivalirudin | Bittl et al74 | 4098 | PCA for unstable or postinfarct angina | IV bolus (1 mg/kg) then IV infusion × 24 h | IV UFH × 24 h | Death, MI, abrupt vessel closure, and cardiac clinical deterioration in-hospital | Biv: 235/2059 (11.4%) | Biv: 82/2161 (3.8%) | |
| UFH: 249/2039 (12.2%) | UFH: 210/2151 (9.8%) | ||||||||
| NS | P = .001 | ||||||||
| REPLACE-275 | 6010 | PCI | IV 0.75 mg/kg bolus then infusion 1.75 mg/kg/h +/- GPIIbIIIa inh‡ | IV UFH + GPIIbIIIa inh‡ | Death, MI, urgent revascularization or major bleeding at 30 d | Biv: 275/2975 (9.2%) | Biv: 71/2993 (2.4%) | ||
| UFH: 299/2991 (10%) | UFH: 123/3008 (4.1%) | ||||||||
| NS | P = .001 | ||||||||
| HERO-276 | 17 073 | STEMI-all received thrombolysis | IV 0.25 mg/kg bolus then infusion × 48 h | IV UFH × 48 h | Death at 30 d | Biv: 919/8516 (10.8%) | Biv: 58/8516 (0.7%) | ||
| UFH: 931/8557 (10.9%) | UFH: 40/8557 (0.5%)† | ||||||||
| NS | NS | ||||||||
ACS indicates acute coronary syndrome; STEMI, ST-elevation MI; CCF, congestive cardiac failure; PCA, percutaneous coronary angioplasty inh, inhibitor.
Included STEMI and ACS non-ST elevation.
Defined as severe bleeding, does not include intracranial hemorrhage.
Administered for duration of procedure.