hirudin and Death--Sudden--Cardiac

In ISAR-REACT 3, 30-day outcomes in 4570 biomarker negative patients undergoing percutaneous coronary intervention (PCI) > or =2 h after pre-treatment with 600 mg of clopidogrel revealed less bleeding with bivalirudin compared with unfractionated heparin, but no difference in 30-day net clinical benefit. The objective of the present analysis was to assess the impact of bivalirudin vs. heparin on 1-year outcomes in ISAR-REACT 3.. The primary outcome for this analysis was the composite of death, myocardial infarction, or target vessel revascularization 1 year after randomization. The composite of death or myocardial infarction was a secondary outcome. At 1 year, the primary outcome occurred in 17.1% of patients assigned to bivalirudin vs. 17.5% assigned to heparin [hazard ratio (HR), 0.98; 95% confidence interval (CI), 0.86-1.13; P = 0.816]. The combined incidence of death or myocardial infarction was 7.7% in the bivalirudin group vs. 6.7% in the heparin group (HR, 1.15; 95% CI, 0.93-1.43; P = 0.200). The mortality rate was 1.9% in the bivalirudin group and 1.7% in the heparin group (HR, 1.10; 95% CI, 0.71-1.70; P = 0.667). At 1 year, no significant differences in the primary outcome were observed with bivalirudin and heparin in any of the subgroups analysed.. Bivalirudin and unfractionated heparin during PCI provide comparable outcomes at 1 year in biomarker negative patients undergoing PCI after pre-treatment with 600 mg of clopidogrel.. URL www.clinicaltrials.gov; Unique identifier NCT00262054.

Topics: Angina Pectoris; Angioplasty; Anticoagulants; Death, Sudden, Cardiac; Double-Blind Method; Female; Heparin; Hirudins; Humans; Infusions, Intravenous; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Peptide Fragments; Recombinant Proteins; Treatment Outcome

Despite use of heparin and aspirin, 5-10% of patients with unstable angina develop myocardial infarction (MI) or refractory angina in the hospital. We tested the hypothesis that recombinant hirudin (lepirudin), a direct thrombin inhibitor, is superior to heparin, an indirect thrombin inhibitor, in patients with acute ischemic syndromes who were receiving aspirin. Patients (n = 10,141) with unstable angina or suspected acute MI without ST-segment elevation were randomly assigned heparin (5,000-U bolus, then 15-U/kg per hour infusion; n = 5,058) or hirudin (0.4-mg/kg bolus, then 0.15-mg/kg per hour infusion; n = 5,083) for 72 hours in a double-blind trial. The primary outcome measure was cardiovascular death or new MI at 7 days. Analysis was by intention to treat. At 7 days, 213 patients (4.2%) in the heparin group and 182 (3.6%) in the hirudin group had experienced cardiovascular death or new MI (relative risk = 0.84; 95% CI = 0.69-1.02; p = 0.077). The number of patients with cardiovascular death, new MI, or refractory angina at 7 days was 340 (6.7%) with heparin and 284 (5.6%) with hirudin (relative risk = 0.82; 95% CI = 0.70-0.96; p = 0.0125). These differences were primarily observed during the 72-hour treatment period (cardiovascular death or MI relative risk = 0.76; 95% CI = 0.59-0.99; p = 0.039; cardiovascular death, MI, or refractory angina relative risk = 0.78; 95% CI = 0.63-0.96; p = 0.019). Although there was an excess of major bleeding with hirudin requiring transfusion (59 [1.2%] vs 34 [0.7%] with heparin; p = 0.01), there was no excess in life-threatening episodes (20 in each group) or strokes (14 in each group). Data from the Organization to Assess Strategies for Ischemic Syndromes (OASIS)-2 trial suggest that a direct thrombin inhibitor, recombinant hirudin, is more effective than an indirect thrombin inhibitor, heparin, in preventing cardiovascular death, MI, or refractory angina. Recombinant hirudin also has an acceptable safety profile in patients with unstable angina or acute MI without ST-segment elevation.

Topics: Adult; Angina, Unstable; Anticoagulants; Aspirin; Death, Sudden, Cardiac; Double-Blind Method; Drug Administration Schedule; Female; Fibrinolytic Agents; Heparin; Hirudin Therapy; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Recombinant Proteins; Recurrence; Risk; Treatment Outcome

The objectives of the Organization to Assess Strategies for Ischemic Syndromes (OASIS) Pilot Study (phase 2) were (1) to compare the efficacy, safety, and feasibility of recombinant hirudin versus unfractionated heparin as short-term therapy in patients with acute coronary syndromes without ST elevation and (2) to compare the efficacy and safety of long-term therapy with warfarin and aspirin versus standard therapy with aspirin alone in the same patient population. Investigators at 31 Canadian centers randomized 909 patients to receive either medium-dose hirudin, low-dose hirudin, or unfractionated heparin. The incidence of the 7-day primary composite outcome of cardiovascular death, new myocardial infarction (MI), or refractory angina was significantly lower among patients who received hirudin than among those assigned to unfractionated heparin. A subset of these patients was subsequently randomized to long-term, low-intensity (international normalized ratio [INR] < 1.5) or moderate-intensity (INR 2-2.5) anticoagulant treatment with warfarin or to standard therapy. In this substudy, promising results were observed in favor of moderate-intensity warfarin. These findings provided the rationale for the design and conduct of the large-scale, phase III OASIS-2 trial.

Topics: Acute Disease; Aged; Angina, Unstable; Anticoagulants; Aspirin; Canada; Death, Sudden, Cardiac; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Electrocardiography; Feasibility Studies; Female; Fibrinolytic Agents; Heparin; Hirudin Therapy; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Pilot Projects; Recombinant Proteins; Recurrence; Registries; Treatment Outcome; Warfarin