Enoxaparin in unstable angina patients who would have been excluded from randomized pivotal trials

J Am Coll Cardiol. 2003 Jan 1;41(1):8-14. doi: 10.1016/s0735-1097(02)02664-5.

Abstract

Objectives: In the present study, we describe the characteristics and examine the anticoagulation levels and safety of subcutaneous enoxaparin in unstable angina (UA)/non-ST-segment elevation myocardial infarction (NSTEMI) patients who would not have been eligible in the Efficacy Safety Subcutaneous Enoxaparin in Non-Q-wave Coronary Events (ESSENCE) and Thrombolysis In Myocardial Infarction (TIMI)-11B trials.

Background: It is not known whether the benefit shown with enoxaparin in the selected population of pivotal trials can be extended to the real world.

Methods: In our center, all patients with UA/NSTEMI are anticoagulated with subcutaneous enoxaparin adjusted to creatinine clearance. Among 515 consecutive patients, we identified 174 who would not have been eligible for ESSENCE or TIMI-11B ("EP" group for excluded patients). We evaluated cardiovascular death or non-fatal myocardial infarction (MI), as well as major and minor bleeding events, at 30 days in the EP group and in patients without any of the exclusion criteria ("NEP" group for non-excluded patients).

Results: This EP group was older, had a higher female/male ratio, and more frequently had a history of MI or a diagnosis of non-Q MI on admission than the NEP group. The distribution of the anti-Xa activity was similar in both groups. The bleeding rates (major and minor) at 30 days were similar in the EP and NEP groups (2.3% vs. 2.9%, respectively, P = NS). On multivariate analysis, the use of glycoprotein IIb/IIIa inhibitors and the presence of hypertension were the only independent predictors of bleeding found in the whole population. Compared with the NEP group, the EP group had a fourfold increased rate of death or MI at 30 days (15.5% vs. 4.1%, p < 0.01). On multivariate analysis, the independent predictors of death or MI at 30 days were NSTEMI on admission, creatinine clearance, and heart failure.

Conclusions: Patients who do not fit the enrollment criteria of ESSENCE/TIMI-11B have higher risk baseline characteristics for both bleeding and ischemic events. In these patients, enoxaparin with dose adjustment to creatinine clearance provides adequate anti-Xa levels and no excess of bleeding.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angina, Unstable / drug therapy*
  • Angina, Unstable / mortality
  • Anticoagulants / administration & dosage*
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use
  • Aspirin / therapeutic use
  • Creatinine / metabolism
  • Drug Monitoring
  • Enoxaparin / administration & dosage*
  • Enoxaparin / adverse effects
  • Enoxaparin / therapeutic use
  • Factor Xa / analysis
  • Female
  • Fibrinolytic Agents / therapeutic use
  • Hemorrhage / chemically induced
  • Hemorrhage / epidemiology
  • Humans
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / mortality
  • Myocardial Ischemia / epidemiology
  • Myocardial Ischemia / etiology
  • Patient Selection
  • Randomized Controlled Trials as Topic
  • Renal Insufficiency
  • Risk Assessment
  • Treatment Outcome

Substances

  • Anticoagulants
  • Enoxaparin
  • Fibrinolytic Agents
  • Creatinine
  • Factor Xa
  • Aspirin