CLINICAL STUDY: ACUTE CORONARY SYNDROMES
Reactivation of ischemic events in acute coronary syndromes: results from GUSTO-IIb
Maria Cecilia Bahit, MD*,
Eric J. Topol, MD, FACC ,
Robert M. Califf, MD, FACC*,
Paul W. Armstrong, MD, FACC ,
Douglas A. Criger, MPH*,
Vic Hasselblad, PhD*,
Amadeo Betriu, MD ,
Jack Hirsh, MD, FACC||,
Diego Ardissino, MD¶ and
Christopher B. Granger, MD, FACC*
* Duke Clinical Research Institute, Durham, North Carolina, USA
Cleveland Clinic Foundation, Cleveland, Ohio, USA
University of Alberta, Edmonton, Alberta, Canada
Hospital Clinic I, Barcelona, Spain
|| McMaster University, Hamilton, Ontario, Canada
¶ Ospedale Maggiore di Parma, Parma, Italy
Manuscript received July 10, 2000;
revised manuscript received November 9, 2000,
accepted December 13, 2000.
Reprint requests and correspondence: Dr. Maria Cecilia Bahit, Duke Clinical Research Institute, PO Box 17969, Durham, North Carolina 27715
bahit001{at}mc.duke.edu
OBJECTIVES
We sought to determine the incidence of and risk factors for thrombotic events early after discontinuing antithrombin therapy in patients with acute coronary syndromes.
BACKGROUND
Discontinuation of treatment with heparin and other thrombin inhibitors in patients with unstable coronary syndromes has related to clinical and biochemical evidence of early reactivation of thrombosis.
METHODS
We studied 8,943 of the 12,142 patients with acute coronary syndromes enrolled in the Global Use of Strategies To Open occluded arteries in acute coronary syndromes trial of hirudin versus heparin. We excluded patients who received no study drug, lacked timing data, died or had myocardial (re)infarction [(re)MI] during study-drug infusion, or began heparin treatment within 2 h after treatment with the study drug was stopped. We assessed the incidence and timing of (re)MI by type and timing of antithrombin treatment.
RESULTS
In all, 215 patients (2.4%) suffered (re)MI, 49 within 12 h of antithrombin therapy discontinuation and 166 between hour 12 and hospital discharge. The duration of infusion did not differ between the hirudin and heparin groups. The rate of early re(MI) after drug therapy discontinuation was significantly higher in patients given heparin versus hirudin (0.8% vs. 0.3%, p = 0.002). Patients with (re)MI had higher mortality at 30 days (23.6% vs. 2.4%, p = 0.001) and 1 year (35.2% vs. 6.7%, p = 0.001) compared with patients without (re)MI.
CONCLUSIONS
The incidence of (re)MI was clustered within 12 h of heparin therapy discontinuation, with the greatest risk within 4 h. There was no evidence of early reactivation of thrombotic events after hirudin. Patients who had (re)infarction had worse outcomes. Better understanding of the mechanism and possible prevention of recurrent thrombosis is needed.
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Abbreviations and Acronyms
| | aPTT | = activated partial thromboplastin time | | CK-MB | = creatine kinase (-MB) | | ECG | = electrocardiographic | | F1.2 | = prothrombin fragment 1.2 | | FRISC | = FRagmin during InStability in Coronary artery disease | | GUSTO-I | = Global Utilization of Streptokinase and TPA (alteplase) for Occluded coronary arteries | | GUSTO-IIb | = Global Use of Strategies To Open occluded arteries in acute coronary syndromes | | OASIS | = Organization to Assess Strategies for Ischemic Syndromes | | (re)MI | = myocardial (re)infarction | | TAT | = thrombin-antithrombin III complex | | TFPI | = tissue-factor pathway inhibitor | | TRIM | = ThRombin Inhibition in Myocardial ischemia |
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