Reactivation of ischemic events in acute coronary syndromes: results from GUSTO-IIb. Gobal Use of Strategies To Open occluded arteries in acute coronary syndromes.
OBJECTIVE
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.
Bahit
M C
MC
Duke Clinical Research Institute, Durham, North Carolina 27715, USA. bahit001@mc.duke.edu
Topol
E J
EJ
Califf
R M
RM
Armstrong
P W
PW
Criger
D A
DA
Hasselblad
V
V
Betriu
A
A
Hirsh
J
J
Ardissino
D
D
Granger
C B
CB
D000368:Aged; D000991:Antithrombins / Q000627:therapeutic use; D003402:Creatine Kinase / Q000032:analysis; D052279:Creatine Kinase, MB Form; D004562:Electrocardiography; D005260:Female; D006493:Heparin / Q000627:therapeutic use; D024764:Hirudin Therapy; D006801:Humans; D007527:Isoenzymes / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence; D012307:Risk Factors; D015996:Survival Rate; D015912:Thrombolytic Therapy; D013927:Thrombosis / Q000209:etiology
D000991:Antithrombins; D007527:Isoenzymes; D011994:Recombinant Proteins; D006493:Heparin; D003402:Creatine Kinase; D052279:Creatine Kinase, MB Form