Percutaneous Coronary Intervention Among Patients Treated With Enoxaparin Versus Unfractionated Heparin Following Fibrinolytic Administration for ST-Elevation MI - PCI-ExTRACT-TIMI 25

Sep 04, 2006
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Trial Sponsor:
Sanofi-Aventis
Date Presented:
01/01/2006
Date Published:
01/01/2007
Date Updated:
09/04/2006
Original Posted Date:
09/04/2006
References

Description:

The goal of the study was to evaluate treatment with enoxaparin compared with unfractionated heparin (UFH) among patients with ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) after initial treatment with fibrinolytic therapy.

Hypothesis:

To determine whether enoxaparin is superior to UFH as adjunctive therapy for patients undergoing PCI for STEMI who initially received fibrinolytic therapy.

Study Design

Study Design:

Patients Enrolled: 4,676
Mean Follow Up: 30 days
Mean Patient Age: Median age 57 years
Female: 18

Patient Populations:

PCI performed by 30 days and enrolled in the ExTRACT-TIMI 25 trial. Trial criteria included: Age ≥18 years; at least 20 minutes of ischemic symptoms at rest within 6 hours before randomization; ST-segment elevation ≥0.1 mV in two limb leads or 0.2 mV in ≥2 contiguous precordial leads or left bundle branch block; and planned administration of fibrinolysis with either streptokinase, tenecteplase, alteplase, or reteplase

Exclusions:

Cardiogenic shock, pericarditis, symptoms of aortic dissection, contraindications to fibrinolysis, administration of a low molecular weight heparin within the prior 8 hours, known renal insufficiency, or anticipated survival <12 months

Primary Endpoints:

Death or nonfatal recurrent MI through 30 days

Drug/Procedures Used:

Patients in the ExTRACT-TIMI 25 trial were randomized in a double-blind manner to enoxaparin throughout the index hospitalization or weight-based UFH for at least 48 hours. Patients in this study were those in the trial who underwent PCI by 30 days (n = 4,676 total; n = 2,272 with enoxaparin and n = 2,404 with UFH).

Principal Findings:

Fibrin-specific lytic was used in 79% of patients, with 21% receiving streptokinase. Anterior MI was present in 41% of patients, and 27% of patients had TIMI risk score of >3. PCI occurred less frequently in the enoxaparin group compared with the UFH group (22.8% vs. 24.2%, p = 0.027) and later after randomization (median 122 hours vs. 109 hours, p = 0.006).

The primary endpoint of death or nonfatal MI occurred in 10.7% of the enoxaparin group and 13.8% of the UFH group (relative risk [RR] 0.77, p = 0.001), driven by a reduction in nonfatal MI (7.8% vs. 10.9%, RR 0.72, p < 0.001). Results were similar in subgroup analysis by time to PCI, anterior MI, diabetes, and lytic used. Among the cohort of patients who underwent PCI on active double-blind study drug (n = 2,178), death or nonfatal MI occurred less frequently in the enoxaparin group (13.0% vs. 16.7%, RR 0.77, p = 0.013).

There was no difference in TIMI major bleeding (1.4% for enoxaparin vs. 1.6% for UFH, RR 0.87, p = 0.56), TIMI minor bleeding (3.3% vs. 2.4%, RR 1.34, p = 0.09), or intracranial hemorrhage (0.2% vs. 0.4%, p = 0.18). Stroke was lower in the enoxaparin group compared with the UFH group (0.3% vs. 0.9%, RR 0.30, p = 0.006).

Interpretation:

Among patients with STEMI treated with fibrinolytic therapy who undergo subsequent PCI, treatment with enoxaparin was associated with a reduction in the primary endpoint of death or nonfatal MI by 30 days compared with UFH.

Enoxaparin was associated with delayed onset of and occurrence of recurrent MI. In addition, there was no adverse safety hazard, with no difference in the frequency of TIMI major or minor bleeding, and actually lower rates of stroke associated with enoxaparin use. Results for both efficacy and safety were similar when the PCI was performed on active blinded study drug.

References:

Gibson CM, Murphy SA, Montalescot G, Morrow DA, Ardissino D, Cohen M, Gulba DC, Kracoff OH, Lewis BS, Roguin N, Antman EM, Braunwald E. Percutaneous coronary intervention in patients receiving enoxaparin or unfractionated heparin after fibrinolytic therapy for ST-segment elevation myocardial infarction in the ExTRACT-TIMI 25 trial. J Am Coll Cardiol 2007;49:2238-46.

Presented by C.M. Gibson, European Society of Cardiology Scientific Congress, September 2006.

Keywords: Thrombolytic Therapy, Risk, Myocardial Infarction, Stroke, Heparin, Fibrinolytic Agents, Percutaneous Coronary Intervention, Intracranial Hemorrhages, Streptokinase, Enoxaparin, Bundle-Branch Block, Tissue Plasminogen Activator, Diabetes Mellitus


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