Thrombolysis in Patients With Unstable Angina Improves the Angiographic but Not the Clinical Outcome - UNASEM

Description:

The goal of this multicenter, randomized, placebo-controlled trial was to evaluate the angiographic and clinical outcomes of treatment with the thrombolytic anistreplase among patients with unstable angina.

Hypothesis:

Thrombolytic therapy may improve clinical and angiographic outcomes among patients with unstable angina.

Study Design

Study Design:

Patients Enrolled: 159
Mean Patient Age: Mean of 57/59 in the intervention/placebo
Female: ~40

Patient Populations:

  • Age 30-70
  • Resting heart rate 50-100
  • Typical history of unstable angina by the Canadian Cardiovascular Society criteria
  • Last episode within 12 hours prior to admission
  • ST depression in two or more inferior leads or three or more precordial leads of at least 0.1 mV, or terminal negative T waves with minimal depth of 0.2 mV in two or more leads

Exclusions:

  • Previous myocardial infarction, percutaneous transluminal coronary angioplasty, or any cardiac surgery
  • Left bundle branch block or accessory bypass tract
  • Left ventricular hypertrophy
  • Use of digitalis with resulting ECG changes
  • Presence of a pacemaker
  • "One hour after admission in the absence of chest pain"
  • Arrhythmia-induced ST-T changes
  • Systolic pressure over 190 or diastolic pressure over 110 within six months of admission
  • Known renal insufficiency
  • Severe valvular disease
  • Class III or IV New York Heart Association heart failure
  • Cardiomyopathy or "any severe concomitant disease"
  • Treatment with streptokinase or anistreplase within one year of admission
  • Aspirin dosage above 1000 mg/day
  • Oral anticoagulant or IV heparin use
  • Recent major surgery, gastrointestinal ulcer bleeding, or genitourinary tract bleeding within three months of admission
  • History of cerebrovascular accident of any kind
  • Recent trauma or cardiac resuscitation
  • Intramuscular injection given within the past 72 hours
  • Bleeding diathesis
  • Diabetic retinopathy, pregnancy, or menstruation
  • Anticipated difficulty with regard to cardiac catheterizations

Primary Endpoints:

Change in coronary artery lesion diameter between the initial and repeat (after 12-28 hours) coronary angiograms

Secondary Endpoints:

  • Mortality, myocardial infarction, recurrent angina, angioplasty, or bypass surgery
  • Major bleeding requiring blood transfusion
  • Overall bleeding

Drug/Procedures Used:

  • 30 U anistreplase
  • Placebo
After randomization, anistreplase was not given if initial angiography demonstrated no coronary lesion greater than 50%, significant left main disease, or if there was interval development of myocardial infarction.

Concomitant Medications:

  • IV nitroglycerin
  • Heparin bolus of 5000 IU, followed by infusion 1000 IU/h titrate to partial thromboplastin time 1.5-2.5x control values
  • Beta-blockers or calcium blockers
  • Aspirin 300 mg/day

Principal Findings:

  • Administration of anistreplase was associated with an 11% decrease in percent diameter stenosis compared with a 3% decrease with placebo (p=0.002).
  • There was no significant difference in measured clinical outcomes.
  • Administration of anistreplase was significantly associated with higher rates of bleeding (26% vs. 9%, p=0.001) and with higher rates of major bleeding (9% vs. 1%).

Interpretation:

Among patients with unstable angina with no history of significant heart disease, the administration of 30 U anistreplase was associated with a significant improvement in percent diameter stenosis at the expense of higher rates of bleeding compared with placebo. There was no association between administration of anistreplase and improved clinical outcomes.

References:

Bar FW, Verheugt FW, Col J, et al. Thrombolysis in patients with unstable angina improves the angiographic but not the clinical outcome. Results of UNASEM, a multicenter, randomized, placebo-controlled, clinical trial with anistreplase. Circulation 1992;86:131-7.

Clinical Topics: Anticoagulation Management, Dyslipidemia, Lipid Metabolism, Novel Agents

Keywords: Thrombolytic Therapy, Myocardial Infarction, Heparin, Constriction, Pathologic, Fibrinolytic Agents, Heart Rate, Calcium, Partial Thromboplastin Time, Anistreplase, Nitroglycerin


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