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GUSTO-V Trial: Global Utilization of Strategies to Open Occluded Coronary Arteries-V
| Study Design |
Prospective, multicenter, randomized, open-label
trial. |
| Sample Size |
n = 16,588 within 6 hours of onset of symptoms
of acute MI, STEMI, or new left bundle branch block (LBBB)
|
| Exclusion Criteria |
Patients with active bleeding, non-compressible
vascular puncture site, blood pressure > 180/110 mm Hg, on oral
anticoagulant therapy, stroke within the preceding 2 years, body weight >120
kg, or platelet count <100,000 cells/uL |
| Interventions |
- n = 8,328: reteplase 10 U x 2
doss (30 minutes apart)
- n = 8,328: abciximab 0.25 mg/kg bolus followed
by 0.125 ug/kg/min for 12 hours + reteplase 5 U x 2 doses (30 minutes apart)
|
| Other Treatments |
- All patients received aspirin
150 mg on enrollment and daily thereafter (75-325 mg/d), intravenous heparin
with a target aPTT of 50-70 seconds.
- Coronary angiography and PCI
or CABG were permitted.
- The use of nonstudy abciximab for patients in
the reteplase alone group was permitted if PCI was performed within 24 hours of
enrollment and recommended if performed >24 hours after enrollment.
|
| Primary Endpoint |
To compare the effects of reteplase alone with a
combination of a reduced dose of reteplase with abciximab in patients with ST segment
elevation acute MI (STEMI).
|
| Results |
- 24 hr-mortality was 2.3% in
the reteplase only group and 2.2% in the reteplase + abciximab group (RR 0.96;
95% CI=0.78-1.18).
- 7-day mortality was 4.5% and
4.3%, respectively (RR 0.97; 95% CI=0.83-1.12).
- 30-day mortality was 5.9% in
the reteplase group vs 5.6% in the reteplase + abciximab group (RR 0.95; 95% CI=0.84-1.08; p=0.37).
- Reinfarction occurred in 3.5%
of the patients in the reteplase group vs 2.3% in the combination group (p<0.0001).
- 20.6% retelplase only vs
16.2% of the patients in the combination group died, experienced reinfarction
or underwent urgent revascularization within the first 7 days (RR 0.75; 95%
CI=0.69-0.81; p<0.0001).
- Severe bleeding occurred in
0.5% in the reteplase group vs 1.1% in the combination group (p<0.0001),
moderate bleeding in 1.8% vs 3.5%, respectively (p<0.0001), and 4.0% vs 5.7%
of the patients, respectively, had transfusion (p<0.0001).
- Intracranial hemorrhage (ICH) occurred in 0.6%
of the patients in the combination group (OR 0.76; 95% CI=0.43-1.37; p=0.37). ICH occurred in 0.6% of the patients in each
group (and patients > 75 years old, intracranial hemorrhage occurred in 1.1%
of the patients in the reteplase group vs 2.1% in the combination group (OR
1.91; 95% CI=0.95-3.84; p=0.069), and in patients < 75 years of age, ICH
occurred in 0.5 % vs 0.4%, respectively (OR 0.76; 95% CI=0.46-1.24; p=0.27).
|
| NNT/NNH |
Severe bleeding with combination therapy was =
167
|
| Conclusions |
The combination of low-dose reteplase + a 12-hour
infusion of abciximab was not found to be superior to standard reteplase
regimen, but reduced secondary end points, including infarction. However, the combination
therapy was also associated higher nonintracranial bleeding complications and a
trend towards an increased risk for intracranial hemorrhage, mainly in patients
> 75 years. |
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