Context In unstable coronary syndromes, catheter intervention is frequently
preceded by antithrombotic treatment to reduce periprocedural risk; however,
evidence from clinical trials to support antithrombotic pretreatment is sparse.
Objective To test the hypothesis that prolonged antithrombotic pretreatment improves
the outcome of catheter intervention in patients with acute unstable coronary
syndromes compared with early intervention.
Design, Setting, and Patients Randomized controlled trial conducted from February 27, 2000, to April
8, 2002, and including patients admitted to 2 German tertiary care centers
with symptoms of unstable angina plus either ST-segment depression or elevation
of cardiac troponin T levels.
Interventions Patients were randomly allocated to antithrombotic pretreatment for
3 to 5 days or to early intervention after pretreatment for less than 6 hours.
In both groups, antithrombotic pretreatment consisted of intravenous unfractionated
heparin (60-U/kg bolus followed by infusion adjusted to maintain partial thromboplastin
time of 60 to 85 seconds), aspirin (500-mg intravenous bolus followed by 100-mg
twice-daily oral dose), oral clopidogrel (600-mg loading dose followed by
75-mg twice-daily dose), and intravenous tirofiban (10-µg/kg bolus followed
by continuous infusion of 0.10 µg/kg per min).
Main Outcome Measure Composite 30-day incidence of large nonfatal myocardial infarction or
death from any cause.
Results Of the 410 patients enrolled, 207 were allocated to receive prolonged
antithrombotic pretreatment and 203 to receive early intervention. Elevated
levels of cardiac troponin T were present in 274 patients (67%), while 268
(65%) had ST-segment depression. The antithrombotic pretreatment and the early
intervention groups were well matched with respect to major baseline characteristics
and definitive treatment (catheter revascularization: 133 [64.3%] vs 143 [70.4%],
respectively; coronary artery bypass graft surgery: 16 [7.7%] vs 16 [7.9%]).
The primary end point was reached in 11.6% (3 deaths, 21 infarctions) of the
group receiving prolonged antithrombotic pretreatment and in 5.9% (no deaths,
12 infarctions) of the group receiving early intervention (relative risk,
1.96 [95% confidence interval, 1.01-3.82]; P = .04).
This outcome was attributable to events occurring before catheterization;
after catheterization, both groups incurred 11 events each (P = .92).
Conclusion In patients with unstable coronary syndromes, deferral of intervention
for prolonged antithrombotic pretreatment does not improve the outcome compared
with immediate intervention accompanied by intense antiplatelet treatment.