Transcript Rimonabant in Obesity - Clinical Trial Results

SURVIVE-W
Survival of Patients with Acute Heart Failure in Need
of Intravenous Inotropic Support
Presented at
The American Heart Association Scientific
Sessions, November 2005
Presented by Dr. Alexandre Mebazaa
SURVIVE-W: Background
• Levosimendan, a calcium-sensitizing agent that has both
vasodilator and inotropic effects, has been proposed as an
alternative to the standard treatment of dobutamine
• Two small pilot trials, LIDO and CASINO, showed lower rates
of mortality with levosimendan compared with dobutamine and
placebo
• The goal of the trial is to compare treatment with levosimendan
to treatment with dobutamine in patients with acute heart failure
who are in need of intravenous inotropic support
• SURVIVE is the first prospective randomized mortality trial of
IV drug therapy in acute decompensated heart failure
www. Clinical trial results.org
SURVIVE-W: Design
1327 patients with acute decompensated heart failure, left ventricular
ejection fraction ≤ 30%, clinical need for inotropic therapy after
intravenous diuretics and/or vasodilators
Levosimendan
Dobutamine
(12 µg/kg bolus plus 0.1-0.2
µg/kg/min infusion for 24 hours)
(≥5 µg/kg/min infusion for ≥ 24
hours)
n=663
n=664
Endpoints:


Primary – All cause mortality at 6 months
Secondary – All-cause mortality at 31 days, BNP at 24 hours, days alive out of
hospital, change in patient dyspnea assessment, change in patient global
assessment
www. Clinical trial results.org
SURVIVE-W: Primary endpoint
35%
All-Cause Mortality at 6 months
(% of treatment arm)
p = 0.401
30%
27.9%
26.1%
25%
20%
15%
10%
• There was no
significant difference
in the primary
endpoint of all-cause
mortality between the
levosimendan and
dobutamine groups
5%
0%
Levosimendan
www. Clinical trial results.org
Dobutamine
ESC 2005
SURVIVE-W: Secondary Endpoint
All-cause mortality at 31 days (% of treatment arm)
15%
HR 0.85; p = NS
13.7%
11.9%
10%
5%
There was no
difference in allcause mortality
between
treatment
groups at 31
days
0%
Levosimendan
www. Clinical trial results.org
Dobutamine
ESC 2005
SURVIVE-W: Post-hoc Analysis
8%
All-cause mortality at 5 days (% of treatment arm)
p = NS
6.0%
6%
4.4%
4%
2%
In a post-hoc
analysis, allcause mortality
at 5 days was
not significantly
different
between
treatment
groups
0%
Levosimendan
www. Clinical trial results.org
Dobutamine
ESC 2005
SURVIVE-W: Limitations
• REVIVE-2, the complement trial to SURVIVE, compared
levosimendan against placebo and showed no mortality
benefit. Thus, although levosimendan is not associated with
increased mortality compared to dobutamine, it does not
improve mortality compared to placebo.
• There was a significant reduction in BNP in the
levosimendan group compared to the dobutamine group.
While BNP is a marker, this study raises questions as to
whether BNP is a surrogate endpoint given that the
treatment was not associated with reduced mortality.
www. Clinical trial results.org
SURVIVE-W: Summary
• Among patients with acute heart failure in need of intravenous inotropic
support, treatment with levosimendan did not significantly reduce all-cause
mortality compared with treatment with dobutamine
• There was no difference in all-cause mortality at 31 days or at 5 days
though in the subgroup of patients with a history of heart failure, mortality
did trend lower at 5 days
• BNP at 24 hours was significantly lower (p=<0.001) in the levosimendan
group compared with the dobutamine group. BNP dropped by almost 50%
after the infusion and stayed low for at least five days
• There were no differences in hypotension or ventricular tachycardia.
However, atrial fibrillation occurred more often in the levosimendan group
(9% vs 6%) while cardiac failure occurred less often in the levosimendan
group (12% vs 17%)
www. Clinical trial results.org
ESC 2005