Study Design

Study Design:

Patients Screened: Not given
Patients Enrolled: 12,142
Mean Follow Up: not given
Mean Patient Age: 65
Female: 30
Mean Ejection Fraction: not given

Patient Populations:

Chest discomfort within the previous 12 hours associated either with transient or persistent ST-segment elevation or depression of more than 0.5mm or with persistent, definite T-wave inversion of more than 1mm

Exclusions:

Warfarin at the time of enrollment
Active bleeding
History of stroke
Renal insufficiency (serum creatinine >2.0 mg/dL (177 æmol/L)
Relative contraindication to hirudin therapy
Systolic blood pressure >200 mmHg
Diastolic blood pressure >110 mmHg
Women of child-bearing potential
If a patient were enrolled and was subsequently found to have a serum concentration > 2.0 mg/dL at base line, the study-drug infusion was discontinued

Secondary Endpoints:

Composite endpoint of death, MI, or disability from stroke. Bleeding complications were classified as follows: severe or life-threatening bleeding was defined as intracranial hemorrhage or bleeding that caused hemodynamic compromise requiring intervention. Moderate was defined as bleeding that required transfusion, but was not associated with any hemodynamic compromise.

Drug/Procedures Used:

The study medication (hirudin or heparin) was infused for a minimum of three and a maximum of five days. Each patient received either heparin and hirudin placebo or hirudin and heparin placebo on a double-blind basis.
Desulfated form of recombant hirudin was initially given in a bolus dose of 0.1 mg/kg of body weight IV, followed by a continuous infusion of 0.1 mg/kg/h.
Heparin was initially given in a bolus dose of 5000 U IV, followed by a continuous infusion of 1000 U per hour.

The activated partial-thromboplastin time was determined before the study drug was infused, at 6 hours, 12 hours, and 24 hours. Then a minimum of once a day during its administration. The activated partial-thromboplastin time was adjusted by using a standard nomogram to maintain the value between 60 and 85 seconds. In patients undergoing coronary intervention during the administration of the study drug, specific guidelines allowed the use of a bolus infusion of heparin or placebo and hirudin or placebo to achieve an activated clotting time of at least 300 to 350 seconds and to preserve the double-blind nature of the study.

Concomitant Medications:

For patients with ST-segment elevation, thrombolytic therapy included either streptokinase (SK) or a regimen of accelerated tissue plasminogen activator (tPA) in which tPA is infused rapidly over a period of 1-1/2 hours so that two thirds of the dose is given in the first 30 minutes. Other adjunctive medications given and procedures performed during hospitalization included aspirin, nitrates (oral, topical, IV), calcium-channel blockers, beta blockers (oral, IV), angiotensin-converting enzyme (ACE) inhibitors, coronary arteriography, percutaneous transluminal coronary angioplasty (PTCA), and coronary-artery bypass grafting (CABG).

Coronary angiography, percutaneous coronary revascularization, and CABG were discouraged for the duration of the study-drug infusion unless there was evidence of recurrent ischemia. For patients undergoing elective CABG, it was recommended that the study drug be stopped six to eight hours before surgery, with heparin therapy initiated (if indicated) on an open basis. In cases of emergency CABG, unblinding of the study drug was permitted to avoid the inappropriate use of protamine and to facilitate the control of hemostasis.