Transcript OmniHeart Feeding Study - Clinical Trial Results

TOSCA-2 Trial
Total Occlusion Study of Canada (TOSCA-2) Trial
Presented at
The American Heart Association
Scientific Sessions 2006
Presented by Dr. Vladimir Dzavik
TOSCA-2 Trial: Background
• The goal of the trial was to evaluate late left ventricular (LV) function and artery
patency associated with percutaneous coronary intervention (PCI) compared
with medical therapy among stable, high-risk patients with persistent total
occlusion of the infarct-related artery post-myocardial infarction (MI).
• The TOSCA-2 study was a subgroup of patients in the larger Occluded Artery
Trial (OAT). In TOSCA-2, patients with persistent total occlusion of the infarctrelated artery 3-28 days post-MI were randomized to PCI with stenting (n=195)
or medical therapy (n=185).
• Follow-up angiography was performed 1 year after MI in 87% (n=332) of the 381
patients.
www. Clinical trial results.org
Presented at AHA 2006
TOSCA-2 Trial: Study Design
381 patients with angiography 3-28 days post-MI with evidence of total occlusion of the
infarct-related artery with poor or absent antegrade flow (TIMI flow grade 0 or 1); and
met a criterion for increased risk, defined as ejection fraction <50%, proximal occlusion
of a major epicardial vessel with a large risk region, or both
Exclusions: NYHA class III or IV heart failure, shock , serum creatinine concentration >2.5 mg/dl, angiographically
significant left main or three vessel coronary artery disease, angina at rest, or severe ischemia on stress testing.
Randomized.
17% female, mean age 58 years, mean follow-up 1 year
Concomitant medications: Aspirin, anticoagulation if indicated, ACE inhibitors, beta-blockers,
and lipid lowering therapy, unless contraindicated
PCI with stenting
n=195


Medical Therapy
n=186
Primary Endpoints: 1) Change in LVEF and 2) infarct-related artery patency
Secondary Endpoints: Change in LVEDVI, LVESVI, and regional wall motion
score
www. Clinical trial results.org
Presented at AHA 2006
TOSCA-2 Trial: Primary Endpoint
Change in LV Ejection Fraction at One Year
(% increase)
p=0.47
5%
4.2%
4%
3.5%
3%
2%
1%
• Change in LV
ejection fraction
(LVEF) at one year
did not differ
between the PCI
and medical
therapy group
(4.2% increase
with PCI vs. 3.5%
increase with
medical therapy,
p=0.47).
0%
PCI
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Medical Therapy
Presented at AHA 2006
TOSCA-2 Trial: Primary Endpoint (cont.)
Infarct-related Artery Patency at One Year (%)
p<0.001
83.0%
80%
60%
40%
25.0%
20%
0%
PCI
www. Clinical trial results.org
• The co-primary
endpoint of patency at
one year was higher in
the PCI group
compared with the
medical therapy group
(83% vs. 25%,
p<0.001).
• Percent diameter
stenosis at one year
averaged 52.5% in the
PCI group and 90.2%
in the medical therapy
group (p<0.001).
Medical Therapy
Presented at AHA 2006
TOSCA-2 Trial: Secondary Endpoint
Change in LV End Diastolic Volume Index (ml/m2)
P=0.07
8
6
4
5.3
3.2
2
0
PCI
www. Clinical trial results.org
Medical Therapy
• Change in the LV enddiastolic volume
index (LVEDVI)
trended lower in the
PCI group compared
to the medical therapy
group (3.2 ml/m2 vs
5.3 ml/m2, p=0.07)
• LV end systolic
volume index
(LVESVI) decreased
by a median of 0.5
ml/m2 in the PCI
group and increased
by 1.0 ml/m2 (p=0.10).
Presented at AHA 2006
TOSCA-2 Trial: Limitations
• In the overall OAT trial, the rate of nonfatal reinfarction trended higher in PCI
treated patients.
• It is unclear whether the tendency for PCI to reduce expansion of the left ventricle
(i.e. the ability of PCI to favorably impact LV remodeling) is of greater or lesser
importance than the trend to toward a higher risk of recurrent MI with PCI.
• It should be borne in mind that a totally occluded artery is obviously at low risk of
re-occlusion.
• The one-year follow-up in the TOSCA-2 study may not be long enough to fully
evaluate long term risks and benefits.
• Although the secondary endpoint of change in LVEDVI did trend toward statistical
significance, this was drawn from a subset of a subset since only 42% of the
TOSCA-2 cohort underwent volume determination studies. This subset of patients
is enriched by patients who survived for one year and may reflect a lower risk
population.
www. Clinical trial results.org
Presented at AHA 2006
TOSCA-2 Trial: Summary
• Among stable, high-risk patients with persistent total occlusion of the
infarct-related artery post-MI, performance of PCI 3-28 days post-MI
was not associated with a difference in LV function; however, higher
rates of patency at one year were observed as compared with
medical therapy.
• This angiographic difference in artery patency did not translate into a
clinical difference in the overall OAT trial, which showed no difference
in the composite of death, reinfarction, or severe heart failure with
PCI compared with medical therapy through a mean follow-up of
three years.
www. Clinical trial results.org
Presented at AHA 2006
TOSCA-2 Trial: Summary (cont.)
• The TOSCA-2 trial was based on the assumption that increased
patency with PCI would improve LV function and remodeling.
• However, the higher patency rate at one year with PCI compared with
medical therapy did not translate into improvements in LVEF. LVEF
actually improved from baseline to one year in both treatment groups.
• Early reperfusion therapy in ST elevation MI has been associated with
reductions in clinical events which has led to the development of the
early open artery hypothesis. However, data from the OAT and
TOSCA-2 studies do not support a late open artery hypothesis for
patients with stable but persistent total occlusion.
www. Clinical trial results.org
Presented at AHA 2006