ACC'09i2 Summit Clinical Trial Summary Slides

1
ACC.09/i2 SummitClinical Trial Summary Slides
2
ABOARD
Trial design This study evaluated a strategy of
immediate vs. next-day cardiac catheterization
and revascularization in patients with NSTE ACS.
Results
(p 0.70)

• Peak troponin-I 2.1 vs. 1.7 ng/ml, p 0.70
• No difference in death/MI/urgent
  revascularization at 30 days
• Length of hospital stay 55 vs. 77 hours, p lt 0.01

2.5
2.1
2
1.7
1.5
ng/ml
Conclusions
1

• A strategy of immediate PCI does not impact the
  incidence of death or MI in NSTE ACS
• Length of hospital stay was significantly reduced
  with an immediate PCI strategy

0.5
0
Peak troponin-I
Immediate PCI (n 175)
Next-day PCI (n 177)


Presented by Dr. Gilles Montalescot at ACC.09/i2,
Orlando, FL
3
ACTIVE A
Trial design This study evaluated treatment
with a combination of aspirin and clopidogrel
versus aspirin alone in patients with AF who were
not candidates for warfarin therapy.
Results
(p lt 0.001)
(p 0.08)

• Stroke/MI/systemic embolus/vascular death 6.8
  vs.7.6 per year, p 0.01
• Stroke 2.4 vs. 3.3 per year, p lt 0.001
• MI 0.7 vs. 0.9 per year, p 0.08
• Major hemorrhage 2.0 vs. 1.3 per year, p lt
  0.001

3.3
3.5
3
2.4
2.5
2
Percent per year
Conclusions
1.5

• Clopidogrel in addition to aspirin may reduce the
  risk of stroke in patients with AF who are
  unsuitable candidates for warfarin therapy
• The increased risk of major hemorrhage with
  aspirin clopidogrel somewhat attenuates this
  benefit

0.9
1
0.7
0.5
0
Stroke
MI
ACTIVE Investigators. N Engl J Med 2009Mar
31Epub
4
ARMYDA-RECAPTURE
Trial design This study evaluated the efficacy
of an atorvastatin reloading strategy in patients
on chronic statin therapy undergoing PCI for
stable angina or NSTEMI.
Results
(p 0.02)
(p 0.04)

• 30-day MACE 3.4 vs. 9.1, p 0.04
• CK-MB elevation 13 vs. 23, p 0.02
• Troponin-I elevation 36 vs. 47, p 0.03
• Peak CRP 2.1 6.7 vs. 3.0 9.5, p 0.12

23
25
20
13
15
Conclusions
Patients
9.1
10

• An 80 mg loading dose of atorvastatin followed by
  a 40 mg preprocedural dose may reduce the
  incidence of post-procedure MACE in patients on
  background statin therapy
• These data support a strategy of routine
  atorvastatin reloading prior to PCI in patients
  on background statin therapy

3.4
5
0
MACE
CK-MB
Presented by Dr. Germano DiSciascio at ACC.09/i2,
Orlando, FL
5
AURORA
Trial design This study evaluated treatment
with 10 mg rosuvastatin compared with standard
therapy in patients with end-stage renal disease
receiving hemodialysis.
Results
(p NS for all comparisons)

• Per 100 patient-years
• CV death 7.2 vs. 7.3, p 0.97
• Nonfatal MI 2.1 vs. 2.5, p 0.23
• Nonfatal stroke 1.2 vs. 1.1, p 0.42
• Composite endpoint 9.2 vs. 9.5, p 0.59

8
7.3
7.2
7
6
5
4
Events per 100 patient-years
Conclusions
2.5
3
2.1

• Low-dose rosuvastatin therapy does not reduce the
  rate of cardiovascular events in patients with
  ESRD receiving hemodialysis

2
1.2
1.1
1
0
CV death
MI
Stroke
Fellstrom B, et al. N Engl J Med 20093601395-407
6
EARLY ACS
Trial design Patients with NSTE ACS were
randomized to upstream eptifibatide and 18- to
24-hour infusion (n 4,722) versus upstream
placebo and provisional eptifibatide immediately
prior to PCI (n 4,684).
Results
(p 0.23)
(p 0.015)

• Death, MI, revascularization, or thrombotic
  bailout at 96 hours 9.3 with upstream
  eptifibatide vs. 10.0 with provisional
  eptifibatide (p 0.23)
• Death or MI at 30 days in 11.2 vs. 12.3 (p
  0.08), respectively
• TIMI major bleeding 2.6 vs. 1.8 (p 0.015),
  respectively

10.0
9.3

2.6
1.8
Conclusions

• Among patients with NSTE ACS treated with
  aspirin, clopidogrel, and heparin, there was no
  benefit to upstream eptifibatide compared with
  provisional use immediately prior to PCI
• Upstream use of eptifibatide increased major
  bleeding

Death, MI, revascularization, or thrombotic
bailout
TIMI major bleeding
Delayed provisional eptifibatide
Upstream eptifibatide


Giugliano RP, et al. N Engl J Med 2009Mar
30Epub
7
FIX-HF-5
Trial design Patients with NYHA III or IV heart
failure and narrow QRS were randomized to cardiac
contractility modulation plus optimal medical
therapy (n 215) vs. optimal medical therapy
alone (n 213).
Results
(p 0.093)

• Anaerobic threshold responder analysis 17.6
  with treatment vs. 11.7 with control (p 0.093)
• Peak VO2 improved by 0.65 ml/kg/min with
  treatment (p 0.024)
• Quality of life improved by -9.7 points with
  treatment (p lt 0.0001)

17.6

11.7
Conclusions

• Among patients with advanced heart failure, low
  ejection fraction, and narrow QRS, cardiac
  contractility modulation failed to improve the
  primary efficacy outcome, anaerobic threshold
• Cardiac contractility modulation did improve peak
  VO2 and quality of life

Anaerobic threshold responder analysis
Cardiac contractility modulation
Control


Presented by Dr. William Abraham at ACC.09/i2,
Orlando, FL
8
GENIUS-STEMI
Trial design Patients with STEMI were randomized
to the endothelial progenitor cell capture stent
(n 50) vs. a cobalt-chromium BMS (n 50).
Follow-up was 6 months.
Results

• MACE 24 with endothelial progenitor cell stent
  vs. 10 with bare-metal stent (p 0.03)
• TLR 14 vs. 4 (p 0.04), respectively
• Stent thrombosis 6 vs. 0 (p NS), respectively

(p 0.03)
(p NS)
24

Conclusions
10
6

• Among patients with STEMI, the endothelial
  progenitor cell capture stent was inferior to a
  cobalt-chromium bare-metal stent
• This experimental stent resulted in increased
  MACE, TLR, and stent thrombosis

0
MACE
Stent thrombosis
Endothelial progenitor cell capture stent
Placebo


Presented by Dr. Pavel Cervinka at ACC.09/i2,
Orlando, FL
9
IRIS
Trial design This study evaluated ICD
implantation early after MI in patients with low
ejection fraction or other high-risk criteria.
Results
(p 0.76)

• Index diagnosis was STEMI in 77
• PTCA in 63 no reperfusion in 25
• All-cause mortality 22.9 vs. 22.0, p 0.76
• Significant reduction in sudden cardiac death and
  significant increase in nonsudden cardiac death
  with ICD implantation

40
35
30
22.9
22.0
25
20
Percent
15
Conclusions
10

• ICD implantation within 31 days after MI did not
  improve mortality over 3-year follow-up
• Routine ICD implantation early after MI cannot be
  recommended at this time

5
0
All-cause mortality
ICD (n 445)
No ICD (n 453)


Presented by Dr. Gerhard Steinbeck at ACC.09/i2,
Orlando, FL
10
NAPLES II
Trial design This study evaluated the
effectiveness of an 80 mg loading dose of
atorvastatin vs. placebo in reducing
periprocedural MI in statin-naïve patients
undergoing elective PCI.
Results
(p 0.01)
(p lt 0.001)

• CK-MB gt3x ULN 9.5 vs. 15.8, p 0.01
• Troponin-I gt3x ULN 26.6 vs. 39.1, p lt 0.001
• Reduction in MI was greatest in patients with
  high CRP
• No difference in death, unplanned
  revascularization, or stent thrombosis

45
39.1
40
35
26.6
30
25
Patients
20
15.8
Conclusions
15
9.5

• Pretreatment with a loading dose of atorvastatin
  may reduce the incidence of postprocedure MI in
  statin-naïve patients undergoing PCI
• Whether a single loading dose of atorvastatin is
  superior to a more extended course prior to PCI
  remains unclear

10
5
0
CK-MB
Troponin-I
Cardiac enzyme elevation gt3x ULN
Presented by Dr. Carlo Briguori at ACC.09/i2,
Orlando, FL
11
OMEGA
Trial design Patients who were 3-14 days out
from an NSTEMI or STEMI were randomized to
omega-3 fatty acids and standard medical therapy
(n 1,940) vs. standard medical therapy alone.
Follow-up was 1 year.
Results
(p 0.84)

• Sudden cardiac death 1.5 for omega-3 fatty
  acids vs. 1.5 for control (p 0.84)
• All-cause mortality 4.6 vs. 3.7, respectively
• MI 4.5 vs. 4.1, respectively
• Arrhythmic events 1.1 vs. 0.7, respectively

1.5
1.5

Conclusions

• Among patients with NSTEMI or STEMI, omega-3
  fatty acids did not reduce the primary outcome,
  sudden cardiac death
• Omega-3 fatty acids also did not appear to change
  any of the secondary outcomes

Sudden cardiac death
?-3 fatty acids
Control


Presented by Dr. Jochen Senges at ACC.09/i2,
Orlando, FL
12
PRIMA
Trial design Patients admitted for worsening HF
and whose NT-proBNP decreased during admission
were randomized to NT-proBNP guided HF management
(n 174) vs. clinically guided management (n
171).
Results
(p 0.49)

• Number of days alive outside the hospital 685
  with NT-proBNP management vs. 664 with control (p
  0.49)
• Total mortality 26.5 vs. 33.0 (p 0.20),
  respectively

685
days
664
Conclusions

• Among patients admitted with decompensated HF,
  NT-proBNP guided therapy did not reduce the
  number of days alive outside the hospital or
  total mortality compared with clinically guided
  management

Days alive outside the hospital
NT-proBNP management
Clinical management


Presented by Dr. Luc Eurlings at ACC.09/i2,
Orlando, FL
13
PROTECT-AF
Trial design Patients with nonvalvular AF were
randomized to percutaneous LA appendage closure
with the Watchman device followed by
discontinuation of warfarin in 45 days (n 463)
vs. continued warfarin therapy (n 244).
Results
(p for non- inferiority lt 0.05)
(p for superiority lt 0.05)

• CV death, stroke, or systemic embolism 3.4
  events per 100 pt-yrs with closure vs. 5.0 events
  per 100 pt-yrs with control (p for
  non-inferiority lt 0.05)
• Hemorrhagic stroke 1 vs. 6 (p for superiority lt
  0.05), respectively
• Composite safety outcome 8.7 events per 100
  pt-yrs vs. 4.2 events per 100 pt-yrs (p for
  superiority lt 0.05), respectively

5.0
8.7
Events per 100 pt-years
4.2
3.4
Conclusions

• In patients with nonvalvular AF, use of Watchman
  for LA appendage closure is feasible
• Device demonstrated noninferior composite
  efficacy, although worse composite safety due to
  pericardial effusion

Composite efficacy
Composite safety
Watchman
Warfarin therapy


Presented by Dr. David Holmes at ACC09/i2,
Orlando, FL
14
REVIVAL-3
Trial design After primary angioplasty, STEMI
patients were randomized to intravenous
erythropoietin (n 68) vs. placebo (n 70).
Follow-up was 6 months.
Results
(p 0.91)

• LVEF at 6 months 52 with erythropoietin vs. 52
  with placebo (p 0.91)
• Death 1.5 vs. 2.9, respectively
• MI 2.9 vs. 1.4, respectively
• Stroke 1.5 vs. 0, respectively
• Stent thrombosis 2.9 vs. 2.9, respectively

52
52

Conclusions

• Among STEMI patients treated with primary PCI,
  the use of high-dose erythropoietin did not
  improve LVEF at 6 months
• Adverse cardiac outcomes were similar between the
  two groups

LVEF at 6 months
High-dose erythropoietin
Placebo


Presented by Dr. Ilka Ott at ACC.09/i2, Orlando,
FL
15
STICH
Trial design This study evaluated CABG with and
without SVR in patients with CAD and
anterior-apical regional ventricular dysfunction.
Results
(p 0.98)
(p 0.90)

• Death or CV hospitalization 58 vs. 59, p
  0.90
• No difference in quality of life, angina
  frequency, angina severity, or depression
• Increased cost with SVR CABG (70,717 vs.
  56,122, p 0.004)

70
59
58
60
50
40
Patients
28
28
30
Conclusions
20

• Routine SVR in addition to CABG does not improve
  cardiovascular morbidity and mortality or quality
  of life compared to CABG alone

10
0
Death
Death or CV
hospitalization
Presented by Drs. Robert Jones Daniel Mark at
ACC.09/i2
16
TIPS
Trial design This study evaluated the efficacy
of the Polycap in controlling cardiac risk
factors in patients at risk for CV disease.
Results
Systolic BP Diastolic BP

• LDL lowering -0.70 mmol/L
• Heart rate lowering -7.0 bpm
• Urinary 11-dehydrothromboxane B2 reduction
  -283.1 ng/mmol creatinine
• Blood pressure lowering -7.4/5.6 mm Hg

Conclusions

• The Polycap was well-tolerated and non-inferior
  to its individual components regarding blood
  pressure and heart rate lowering
• In terms of LDL cholesterol lowering and platelet
  inhibition, the Polycap did not achieve
  prespecified noninferiority criteria compared
  with simvastatin and aspirin alone

(p lt 0.0001 for noninferiority)
TIPS Investigators. Lancet 2009Mar 30Epub
before print
17
ZEST
Trial design Patients with CAD undergoing PCI
were randomized to ZES (n 883), SES (n 878),
or PES (n 884). Follow-up was 12 months.
Results

• Death, MI, or TVR 10.1 with ZES, 8.3 with SES,
  and 14.2 with PES (p 0.25 for ZES vs. SES, p lt
  0.0003 for ZES vs. PES)
• TLR 4.9 vs. 1.4 vs. 7.6 (p lt 0.001 for ZES
  vs. SES, p 0.005 for ZES vs. PES), respectively
  for ZES, SES, and PES

14.2

10.1
8.3
7.6
4.9
Conclusions
1.4

• Among patients with CAD, including a lot of ACS,
  zotarolimus resulted in similar adverse cardiac
  events compared with sirolimus, although less
  events compared with paclitaxel
• Lowest TLR observed with sirolimus intermediate
  with zotarolimus, and highest with paclitaxel

Death, MI, or TVR
TLR
ZES
SES
PES



Presented by Dr. Seung-Jung Park at ACC09/i2,
Orlando, FL