Transcript reviparin - Clinical Trial Results

CREATE-ECLA - Reviparin
Impact of Low-molecular-weight Heparin (Reviparin)
on Mortality, Reinfarction, and Stroke in Patients
with Acute MI
Presented at:
American Heart Association
Scientific Sessions 2004
Presented by: Dr. S.D. Yusuf
CREATE-ECLA - Reviparin
15,570 acute MI patients presenting within 12 hours of symptom onset
Enrolled exclusively in India and China
6% received PCI, 73% thrombolytic therapy (primarily streptokinase and urokinase)
97% Aspirin, 72% ACE inhibitors, 66% beta-blockers, 66% lipid-lowering therapy, 55% clopidogrel
Also randomized to GIK or control – results presented separately
Reviparin
Placebo
(low-molecular-weight heparin)
Subcutaneous injections for 7 days
Weight-adjusted doses:
<50 kg
3436 IU
50-75 kg
5153 IU
>75 kg
6871 IU
 n=7,790
Mean onset-to-treatment = 4.8 hr
 n=7,780
Mean onset-to-treatment = 4.9 hr
Primary Endpoints: Death, MI, or stroke at 7 days; death, MI, stroke, or
recurrent ischemia with ECG changes at 7 days.
Secondary Endpoints: above endpoints at 30 days
www. Clinical trial results.org
Presented at AHA 2004
CREATE-ECLA –Reviparin: 7-day results
Death/MI/stroke and
Death/MI/stroke/ischemia at 7 days
• The primary composite
15
p=0.0039
p=0.0049
%
10
12.6
11.1
11.0
9.6
endpoints of 7-day
death/MI/stroke and
death/MI/stroke/ischemia
were significantly lower in
the Reviparin group
compared to the placebo
group
5
0
Death/MI/stroke
Death/MI/stroke/ischemia
Reviparin
www. Clinical trial results.org
Placebo
Presented at AHA 2004
CREATE-ECLA –Reviparin 7-day results
Treatment with Reviparin was associated with a significant reduction in the
individual primary endpoints of death and recurrent MI at 7 days. The two
treatments were not significantly different in the occurrence of stroke.
10
p=0.0357
8.9
8.0
8
p=0.018
%
6
p= NS
4
2.1
1.6
2
0.8
0.6
0
Death
MI
Reviparin
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Stroke
Placebo
Presented at AHA 2004
CREATE-ECLA –Reviparin: 30-day results
Death/MI/stroke and
Death/MI/stroke/ischemia at 30 days
20
p=0.0016
p=0.0014
15
15.6
13.8
13.6
11.8
10
• The secondary composite
endpoints of 30-day
death/MI/stroke and
death/MI/stroke/ischemia were
significantly lower in the
Reviparin group compared to
the placebo group.
%
• The individual endpoints of
Death and MI were also
significantly lower in the
Reviparin group at 30 days.
5
0
Death/MI/stroke
Death/MI/stroke/ischemia
Reviparin
www. Clinical trial results.org
Placebo
Presented at AHA 2004
CREATE-ECLA –Reviparin: Safety
Bleeding at 7 days
1
0.9 p=<0.001
p=<0.001
1
1
major bleeding and lifethreatening bleeding alone at
7 days were both significantly
higher with Reviparin
compared with placebo
0.7
1
1
1
0.4
%
0
• Life-threatening bleeding and
0.3
0
0
0
0
Life-threatening or major
bleeding
Life-threatening bleeding
Reviparin
www. Clinical trial results.org
Placebo
Presented at AHA 2004
CREATE-ECLA –Reviparin: Summary
• Among acute MI patients presenting within 12 hours of onset of symptoms, treatment with the lowmolecular-weight heparin reviparin was associated with a significant reduction in the primary composite
endpoints of 7-day death/MI/stroke and death/MI/stroke/ischemia compared with placebo. The results were
maintained at 30-days
• The reduced primary composite endpoints at both 7 and 30 days were due to lower individual endpoints of
death and recurrent MI in the reviparin group; the two treatments were not significantly different in incidence
of stroke
• Small but significant increases in 7-day life-threatening bleeding/major bleeding and life-threatening
bleeding alone occurred in the reviparin arm
• There was a significant association between time-to-treatment and efficacy, with no effect seen in patients
treated after 8 hours from symptom onset.
• Treatment occurred entirely in India and China and differed from standard Western practice in several
ways, including a reduced number of patients receiving primary PCI and reliance on thrombolytics not often
used in the US (streptokinase and urokinase)
• The study is the first large randomized trial to show a significant reduction in mortality with a low molecular
weight heparinoid drug when given in addition to reperfusion therapy and aspirin in patients with acute MI
•The ongoing EXTRACT trial is looking for a similar reduction in mortality in acute MI patients treated with
another low-molecular-weight heparin, enoxaparin
www. Clinical trial results.org