Some results from PROTECT. Generally looks quite good for I. Any views on whether or not this should lead to increased ER usage of I?
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New Data Reveal Clinical Differences Between INTEGRILIN (R) (Eptifibatide) Injection and Bivalirudin
prnews
NEW ORLEANS, Nov. 6 /PRNewswire-FirstCall/ -- Millennium Pharmaceuticals,
Inc. (Nasdaq: MLNM) announced results of the PROTECT trial, which was designed
to compare the glycoprotein (GP) IIb-IIIa inhibitor INTEGRILIN with the direct
thrombin inhibitor bivalirudin in high risk patients using clinical and
physiologic endpoints. On the physiologic primary endpoint of coronary flow
reserve (CFR), a measure of coronary artery flow, adjusted as pre-specified,
the primary endpoint favored bivalirudin but was not statistically significant
when imputed as pre-specified for abrupt closure, no reflow, and thrombotic
bail-out during percutaneous coronary intervention (PCI) (p=0.036 by
intent-to-treat; p=0.13 imputed, 1.43 bivalirudin versus 1.33 pooled
INTEGRILIN, respectively). However, INTEGRILIN showed a statistically
significant (p=0.048, adjusted for baseline as pre-specified) improvement in
myocardial perfusion (a measure of blood flow to the heart muscle) compared to
bivalirudin. Myocardial perfusion has been shown to correlate highly with
improved survival.(1)
"A key finding from this study is that better cardiac blood flow resulted
in better clinical outcomes. While the overwhelming majority of patients
(over 93%) left the cath lab with normal flow in the artery, INTEGRILIN
significantly improved flow downstream into the heart muscle itself, as
measured by TIMI Myocardial Perfusion Grade (TMPG)," said C. Michael Gibson,
MS, MD, principal investigator in the PROTECT study and Associate Chief of
Cardiology in the Cardiovascular Division of Beth Israel Hospital at Harvard
Medical School. "This study adds to the growing body of scientific literature
linking improved blood flow into the heart muscle with improved clinical
outcomes. Further, this study highlights the importance of arriving to the
cath lab with good flow to the muscle."
Previous studies have shown up to a seven-fold increase in 30-day
mortality following heart attack in patients whose flow in the artery was
normal but whose myocardial perfusion was rated TMPG 0 or 1, versus those who
demonstrated normal TMPG 3.(2) TMPG measurement shows how effectively blood
flow is restored to the heart muscle following therapeutic and mechanical
intervention. In the PROTECT study, when compared to those acute coronary
syndrome (ACS) patients who received bivalirudin, 13.8% more INTEGRILIN-
treated patients achieved normal perfusion TMPG 3, a statistically significant
benefit (p=0.048 adjusted for baseline as pre-specified).
In addition, in the PROTECT study, other endpoints showed that among
patients with ischemia, INTEGRILIN(R) (eptifibatide) Injection showed a
statistically significant reduction in median duration of ischemia in the
first 24 hours post-PCI versus bivalirudin (36 minutes versus 169 minutes,
p=0.013). Furthermore, measurement of troponin and CK-MB, important protein
and enzymatic markers of cardiac damage, directionally showed lower peak rises
among those patients who received INTEGRILIN. In the subset of the highest
risk ACS patients, those with inadequate blood flow to the heart muscle upon
arrival in the catheterization lab (TMPG 0, 1 or 2), high troponin levels at
baseline correlated significantly with impaired blood flow. Post-PCI,
patients who received INTEGRILIN in this sub-group had a significantly lower
elevation in troponin and CK-MB post-PCI versus those who received bivalirudin
(3.5 vs. 5.3, p=0.04, 2.7 vs. 10, p=0.009, respectively), signifying a
possible reduction in heart muscle damage with use of INTEGRILIN.
Across all patient groups, only 18 of the 857 patients (2%), experienced
any TIMI major or minor bleeding event. In the major safety endpoint for the
trial there was no reported TIMI major bleeding in the INTEGRILIN arm with UFH
or in the bivalirudin arm. There was a 1.5% incidence of TIMI major bleeding
in the INTEGRILIN arm with enoxaparin. TIMI minor bleeding was 2.5% in the
pooled INTEGRILIN arms compared to 0.4% in the bivalirudin arm (p=0.027).
"All clinical efficacy outcome measures in this trial favored INTEGRILIN
over bivalirudin," said Nancy Simonian, MD, senior vice president, clinical
development at Millennium Pharmaceuticals, Inc. "This study reinforces the
need for early and aggressive use of INTEGRILIN in ACS patients to preserve
the heart muscle and protect against future cardiac events."
About PROTECT
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