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2008 Clinical Trial Summary Slides. ACC Annual Scientific Session AHA Scientific Sessions ESC Congress. ACC.08/SCAI-ACCi2 Clinical Trial Summary Slides. ACCOMPLISH. Systolic blood pressure ↓ by amlodipine/benazapril, compared with HCTZ/benazapril by 0.7 mm Hg (p < 0.05)

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Acc annual scientific session aha scientific sessions esc congress l.jpg

2008 Clinical Trial Summary Slides

ACC Annual Scientific Session

AHA Scientific Sessions

ESC Congress


Acc 08 scai acci2 clinical trial summary slides l.jpg

ACC.08/SCAI-ACCi2 Clinical Trial Summary Slides


Accomplish l.jpg

ACCOMPLISH

Systolic blood pressure ↓ by amlodipine/benazapril, compared with HCTZ/benazapril by 0.7 mm Hg (p < 0.05)

Primary endpoint : CV mortality, stroke, MI, revascularization, unstable angina, resuscitation from death 9.2% in amlodipine/benazapril arm, compared with 11.4% in HCTZ/benazapril arm (p = 0.0002)

(p = 0.0002)

Trial design:Patients with hypertension were randomized to fixed dose amlodipine/benazapril or hydrochlorothiazide (HCTZ)/benazapril. Patients were followed for 3 years.

Results

11.4

9.2

12

8

%

Conclusions

4

  • Fixed dose combination of amlodipine/benazapril is better than HCTZ/benazapril in reduction in blood pressure as well as cardiovascular endpoints in patients with high-risk hypertension

0

Primary endpoint

HCTZ/benazapril

(n = 5,721)

Amlodipine/benazapril

(n = 5,741)

Presented by Dr. Kenneth Jamersonat SCAI-ACC i2 Summit/ACC 2008


Slide4 l.jpg

Adjusted Clopidogrel Loading Doses According to VASP Phosphorylation Index Decrease Rate of Major Adverse Cardiovascular Events in Patients With Clopidogrel Resistance

86% of VASP-guided patients overcame resistance with 1-3 extra clopidogrel doses

MACE: 0% for VASP-guided vs. 9.5% for control (p =0.007)

Total bleeding: 3.9% vs. 4.8%, respectively (p = 1.0)

(p = 0.007)

(p = 1.0)

0

9.5

%

3.9

4.8

MACE

Total bleeding

VASP-guided extra clopidogrel

(n = 78)

No extra clopidogrel

(n = 84)

Trial design:Patients with clopidogrel resistance (VASP index >50%) randomized to VASP-guided extra clopidogrel dosing (n = 78) or PCI without add’l clopidogrel (n = 84).

Results

Conclusions

  • Clopidogrel resistance was reversed with VASP-guided additional clopidogrel dosing

  • Effective response to clopidogrel resulted in less MACE and similar bleeding

Bonello L, et al. J Am Coll Cardiol 2008;51: [Published online 29 March 2008]


Slide5 l.jpg

A-F

In-hospital MACE: 11.7% with FilterWire vs. 9.5% with standard PCI (p = ns)

30-day MACE: 12% vs. 11% (p = ns), respectively

TIMI 3 flow post-PCI: 94% vs. 94% (p = ns), respectively

Trial design: NSTEMI patients were randomized to PCI plus FilterWire EZ embolic protection (n = 77) or standard PCI without embolic protection (n = 74).

Results

(p = ns)

(p = ns)

94

94

%

11.7

9.5

Conclusions

In-hospital MACE

TIMI 3 flow post-PCI

  • FilterWire EZ embolic protection is not beneficial in NSTEMI

  • PCI plus FilterWire results in similar in-hospital MACE, 30-day MACE, and TIMI 3 flow post-PCI compared with standard PCI

PCI plus embolic protection

Standard PCI

Presented by Dr. Mark Webster at SCAI-ACC i2 Summit/ACC 2008


Allay l.jpg

ALLAY

Change in LV mass index 4.9 ± 1, 4.8 ± 1, and 5.8 ± 0.9 with aliskiren, losartan, and combination, respectively (all p < 0.0001 compared with baseline)

Aliskiren was noninferior to losartan (p < 0.0001), but combination not superior to losartan alone (p = 0.52)

Incidence of serious side effects was similar (p = 0.77)

Trial design: Overweight hypertensive patients with evidence of left ventricular (LV) hypertrophy were randomized to aliskiren, losartan, or the combination. Patients were followed for 36 weeks to assess the change in LV mass index on cardiac MRI.

Results

(p < 0.0001*)

(p = 0.52**)

4.9

4.8

5.8

6

4

g/m2

Conclusions

2

  • Aliskiren was noninferior to losartan in reducing LV mass index, but the combination was not superior to losartan alone

  • Clinical outcomes studies are awaited

0

Primary endpoint

Aliskiren

(n = 154)

Losartan

(n = 152)

Combination

(n = 154)

* Aliskiren vs. losartan for noninferiority

** Combination vs. losartan

Presented by Dr. Scott Solomonat SCAI-ACC i2 Summit/ACC 2008


Armyda reload l.jpg

ARMYDA-RELOAD

Approximately one-third had unstable angina

MACE in entire study: 7% in reload group vs. 9% in placebo group (p = 0.70)

MACE in ACS patients: 7% vs. 18% respectively, (p = 0.035)

No major bleeds in either group

Trial design:Patients on chronic clopidogrel therapy (>10 days) undergoing PCI were randomized to an additional 600 mg clopidogrel dose (n = 285) or placebo (n = 283) and followed for 30 days.

Results

(p = 0.70)

(p = 0.035)

7

18

7

9

%

Conclusions

MACE in entire study population

MACE in ACS patients

  • Among unselected patients on chronic clopidogrel, no benefit with reloading

  • Clopidogrel reloading may be of benefit in unstable patients

  • Favorable bleeding profile with reloading

Clopidogrel reload

No reload

Presented by Dr. Germano Di Sciascio at

SCAI-ACC i2 Summit/ACC 2008


Astral l.jpg

ASTRAL

Baseline creatinine, 2.02 mg/dl; glomerular filtration rate, 40 ml/min; mean stenosis, 76%; anti-hypertensive medications, 2.8 per patient

93% of revascularized patients received a stent

At follow-up, no difference in creatinine, blood pressure, time to first renal event, or mortality (p = ns for all outcomes)

Trial design:Patients with significant renal artery stenosis were randomized to angioplasty and/or stenting plus medical therapy (n = 403) or medical therapy alone (n = 403) and followed for 27 months.

Results

(p = ns)

(p = ns)

12

14

7.4

8.2

%

Conclusions

Cardiovascular mortality

Hospitalization for fluid overload or heart failure

  • Renal artery revascularization is not superior to medical therapy alone

  • Renal artery stenting does not reduce creatinine, blood pressure, time to first renal event, adverse cardiac events, or mortality

Renal stenting

Medical therapy

Presented by Dr. Philip Kalra at SCAI-ACC i2 Summit/ACC 2008


Atheroma l.jpg

ATHEROMA

Significant reduction from baseline in USPIO-defined signal intensity was observed in 80 mg group at 6 and 12 weeks; no difference was observed in low-dose arm at 6 and 12 weeks

Mean signal difference at 12 weeks between the two groups was 0.24 (p < 0.0001)

(p < 0.0001)

Trial design:Patients with carotid stenosis >40% and who demonstrated intraplaque accumulation of ultra small super-paramagnetic iron oxide (USPIO) on MRI at baseline were randomized to either 10 mg or 80 mg atorvastatin daily for 12 weeks.

Results

0.5

0.20

0.038

0.4

0.3

Units

Conclusions

0.2

  • Aggressive lipid-lowering therapy with 80 mg of atorvastatin daily is associated with significant reduction in USPIO-defined inflammation in carotid plaques

  • USPIO-defined inflammation represents a novel imaging biomarker

0.1

0

Signal intensity at 12 weeks

Atorvastatin 10 mg

(n = 20)

Atorvastatin 80 mg

(n = 20)

Presented by Dr. Tjun Tangat SCAI-ACC i2 Summit/ACC 2008


Brave 3 l.jpg

BRAVE 3

Mean final infarct size: 15.7% vs. 16.5% in the abciximab and control groups (p = 0.47)

Death, MI, stroke or urgent revascularization: 5.0% vs. 3.8% in the abciximab and control groups (p = 0.39)

(p = 0.47)

Abciximab

(n = 401)

Placebo

(n = 399)

Trial design:Patients with STEMI undergoing PCI were randomized to either abciximab or unfractionated heparin (UFH), after pretreatment with 600 mg of clopidogrel. LV infarct size was evaluated at 5-7 days.

Results

20

15.7

16.5

18

16

%

Conclusions

14

  • No difference in infarct size or clinical outcomes with abciximab in patients with STEMI undergoing PCI following pretreatment with 600 mg of clopidogrel

12

10

Final infarct size

Presented by Dr. Julinda Mehilli at SCAI-ACC i2 Summit/ACC 2008


Eclipse l.jpg

ECLIPSE

50% interventional procedures; 89% device success

Time to hemostasis: 4.4 min for closure device and 20.1 min for manual pressure (p < 0.0001)

Hematoma >6 cm: 1.9% vs. 0.7% (p = 0.67), respectively

Trial design:Patients with diagnostic and interventional coronary/peripheral procedures were randomized to the ExoSeal closure device (n = 267) or manual pressure (n = 134).

Results

(p < 0.0001)

(p = 0.67)

4.4

20.1

1.9

0.7

min

%

Conclusions

Time to hemostasis

Large (>6 cm) hematoma

  • The ExoSeal closure device reduces time to hemostasis compared with manual pressure

  • No adverse events in either group

  • Nonsignificant increase in large hematomas with ExoSeal closure device

Closure device

Manual pressure

Presented by Dr. Shing-Chiu Wong at

SCAI-ACC i2 Summit/ACC 2008


Enhance l.jpg

ENHANCE

Mean carotid IMT 0.0058 ± 0.0037 mm in the simvastatin arm vs. 0.0111 ± 0.0038 mm in the ezetimibe/simvastatin arm (p = 0.29)

Mean LDL levels 192.7 mg/dl (39% ↓) in simvastatin arm, 141.3 mg/dl in the ezetimibe/simvastatin arm (56% ↓) (p < 0.01)

(p = 0.20)

(p < 0.01)

Ezetimibe/ Simvastatin

(n = 357)

Simvastatin

(n = 363)

Trial design:Patients with heterozygous familial hypercholesterolemia were randomized to treatment with ezetimibe/simvastatin 10/80 mg or simvastatin 80 mg alone. Mean change in intima-media thickness (IMT) was measured in the carotid arteries over 2 years.

Results

4.7

5

193

4

200

2.8

141

3

150

%

mg/dl

2

Conclusions

100

  • No additional benefit in carotid IMT reduction at 2 years with ezetimibe/simvastatin compared with high-dose simvastatin alone

  • LDL lowering greater with ezetimibe/simvastatin

  • Clinical outcomes and adverse events similar

1

50

0

0

LDL cholesterol

New plaque formation

Kastelein JJ, et al. N Engl J Med 2008;358:1431-43


Genesis l.jpg

GENESIS

In-stent late loss: 1.40 ± 0.67 mm, 0.96 ± 0.73 mm, and 0.58 ± 0.58 mm in CORIO, SYMBIO, and CoStar arms, respectively

6-month MACE: 39.0% vs. 14.4% vs. 2.0% for CORIO, SYMBIO, and CoStar arms

Trial design: In this single-blinded study, patients were randomized 2:2:1 to CORIO (pimecrolimus-eluting), SYMBIO (pimecrolimus- and paclitaxel-eluting), or CoStar (paclitaxel-eluting) control arm.

Results

39.8

20.4

7.1

40

30

Conclusions

  • First trial to successfully demonstrate dual drug delivery in patients with CAD undergoing PCI

  • Pimecrolimus ± paclitaxel is associated with higher incidence of in-stent restenosis and MACE compared with paclitaxel alone

20

%

10

0

In-stent restenosis

CORIO

(n = 100)

SYMBIO

(n = 101)

CoStar

(n = 49)

Presented by Dr. Stefan Verheyeat SCAI-ACC i2 Summit/ACC 2008


Slide14 l.jpg

HAT

All-cause mortality: 6.4% for AED and CPR vs. 6.5% for CPR alone (p = 0.77)

37.6% of deaths were due to tachyarrhythmia, with remainder due to heart failure or noncardiac causes

Only 8 patients in each group were resuscitated at home

Trial design:Intermediate-risk patients after an anterior myocardial infarction were randomized to automated external defibrillator (AED) and cardiopulmonary resuscitation (CPR) (n = 3,495) versus CPR alone (n = 3,506) and followed for 37 months.

Results

(p = 0.77)

6.4

6.5

%

Conclusions

All-cause mortality

  • AED and CPR are not superior to CPR alone in intermediate-risk patients after an MI

  • Relatively few deaths in this population are due to tachyarrhythmia

AED and CPR

CPR alone

Bardy GH, et al. N Engl J Med 2008;358:1793-804.


Horizon hf l.jpg

HORIZON-HF

Systolic blood pressure: ↑ 10 mm Hg with 1.5 mcg/kg/min Istaroxime and ↑ 0.6 mm Hg with placebo (p < 0.001)

Cardiac index: +0.3 L/min/m2 vs. -0.01 L/min/m2 (p = 0.04), respectively

LV end-diastolic volume: -14.1 ml vs. +3.9 ml (p = 0.02), respectively

Trial design:Decompensated heart failure patients were randomized to Istaroxime, an inotropic and lusitropic agent (n = 29 for 0.5 mcg/kg/min; n = 30 for 1.0 mcg/kg/min; n = 30 for 1.5 mcg/kg/min) or placebo (n = 31).

Results

(p = 0.04)

(p = 0.02)

+0.3

-0.01

-14.1

+3.9

L/min/m2

ml

Conclusions

  • In this dose-finding study, Istaroxime 1.5 mcg/kg/min may be beneficial in improving hemodynamics and diastolic function in patients with decompensated heart failure

Cardiac index

Left ventricular end-diastolic volume

Istaroxime, 1.5 mcg/kg/min

Placebo

Presented by Dr. Mihai Gheorghiade at the SCAI-ACC i2 Summit/ACC 2008


Hyvet l.jpg

HYVET

Trial was terminated early

Stroke ↓ 30% (p = 0.06), mortality ↓ 21% (p = 0.02), heart failure ↓ 64% (p < 0.001) in indapamide arm compared with placebo

Number needed to treat at 2 years: 94 for stroke, 40 for mortality

(p = 0.02)

(p = 0.06)

Indapamide

(n = 1,933)

Placebo

(n = 1,912)

Trial design: Hypertensive geriatric (age >80 years) patients were randomized to indapamide SR 1.5 mg or to placebo. Clinical outcomes were evaluated at 2 years.

Results

15

5

2.6

3.6

10.1

12.3

4

10

3

%

%

2

Conclusions

5

  • Significant mortality benefit with treatment of BP >160 mm Hg in patients older than 80 years

  • Newer guidelines will need to consider this group of patients specifically

1

0

0

Strokes

Mortality

Presented by Dr. Nigel Beckett at SCAI-ACC i2 Summit/ACC 2008


Isar react 3 l.jpg

ISAR-REACT 3

Primary endpoint: death, MI, urgent target vessel revascularization, or in-hospital major bleeding was similar between the bivalirudin (8.3%) and UFH (8.7%) arms (p = 0.57)

Bleeding significantly ↓ with bivalirudin compared with UFH: major (33%), minor (31%)

(p = 0.57)

(p = 0.008)

8.3

8.7

3.1

4.6

10

5

8

4

7

6

3

%

%

5

2

4

3

2

1

0

0

Bivalirudin

(n = 2,289)

UFH

(n = 2,281)

Trial design:Troponin-negative patients undergoing PCI were randomized to either bivalirudin or unfractionated heparin (UFH), after pretreatment with 600 mg of clopidogrel. Clinical outcomes were evaluated at 30 days.

Results

9

Conclusions

  • Bivalirudin is not superior to UFH as adjunct anticoagulation therapy for troponin-negative patients undergoing PCI, who were pretreated with 600 mg of clopidogrel

  • Bleeding was significantly reduced with bivalirudin compared with UFH

1

Composite endpoint

Major bleeding

Presented by Dr. Adnan Kastrati at SCAI-ACC i2 Summit/ACC 2008


Mend cabg ii l.jpg

MEND-CABG II

Median aortic cross-clamp time of 1.0 hour, internal mammary artery graft used in 90%

Death or nonfatal MI: 9.3% in MC-1 group and 9.0% in control (p = 0.76)

All-cause mortality: 1.0% vs. 0.3% at 4 days (p = 0.03) and 1.9% vs. 1.5% at 30 days (p = 0.44), respectively

Trial design:Intermediate-risk patients undergoing CABG were randomized to MC-1 (n = 1,519) or placebo (n = 1,504) and followed for 30 days after surgery.

Results

(p = 0.03)

(p = 0.44)

1.9

1.5

1

0.3

%

Conclusions

  • In intermediate-risk patients undergoing CABG, MC-1 is not superior to placebo

  • MC-1 does not reduce death or MI at 30 days

  • MC-1 increased 4-day mortality; however, no difference at 30 days

4-day mortality

30-day mortality

MC-1

Placebo

Alexander JH, et al. JAMA 2008;299:1777-87


Momentum l.jpg

MOMENTUM

Cardiac index: increased to more than 2.4 L/min/m2 (p < 0.0001) with the device

Death or heart failure hospitalization at 65 days: similar between the two groups (p = ns)

Major bleeding: 16.5% vs. 5.1% (p = 0.05), respectively

Trial design:Patients with refractory heart failure symptoms were randomized to the Orqis continuous aortic flow augmentation device for 4 days (superimposing low-level continuous flow on pulsatile flow) (n = 109) or continued medical management (n = 59).

Results

(p = 0.005)

(p = 0.005)

16.5

5.1

26.6

8.5

%

Conclusions

  • Continuous aortic flow augmentation for 4 days increases cardiac index, although death or heart failure hospitalization is similar

  • Major and minor bleeding are increased with the device

Major bleeding

Minor bleeding

Continuous aortic flow augmentation

Medical management

Presented by Dr. Barry Greenberg at SCAI-ACC i2 Summit/ACC 2008


Ontarget l.jpg

ONTARGET

Telmisartan (16.7%) noninferior; combination (16.3%) not superior to ramipril (16.5%) for primary endpoint (CV death, MI, stroke, heart failure)

Greater incidence of hypotension in combination (4.8%) and telmisartan (2.7%) groups, compared with ramipril group (1.7%) (p < 0.001)

(p < 0.004*)

(p = ns)

Trial design:Patients at high risk for cardiovascular events, but without heart failure, were randomized to telmisartan, ramipril, or the combination. Patients were followed for a median of 56 months.

Results

16.7

16.3

16.5

11.6

12.5

11.8

15

20

%

10

10

%

5

Conclusions

  • Either telmisartan or ramipril, but not both, can be used in hypertensive patients at high risk for cardiovascular events

  • Side effects greater with combination therapy

0

0

Primary endpoint

Mortality

Telmisartan

(n = 8,542)

Combination

(n = 8,502)

Ramipril

(n = 8,576)

* Telmisartan vs. ramipril for noninferiority

The ONTARGET investigators. N Engl J Med 2008;358:1547-59


On time 2 l.jpg

ON-TIME 2

Mean transportation distance: 25 km

>3 mm ST-elevation post-PCI: 36.6% with tirofiban and 44.3% with placebo (p = 0.026)

Mortality: 2.3% vs. 4.0% (p = 0.14), respectively

Major bleeding: 4.0% vs. 2.9% (p = 0.36), respectively

Trial design:STEMI patients who presented to a non-PCI center were randomized to tirofiban prior to transfer for primary PCI (n = 491) or placebo with provisional tirofiban in the catheterization laboratory(n = 493) and followed for 30 days.

Results

(p = 0.026)

(p = 0.14)

36.6

44.3

%

2.8

4.0

Conclusions

  • In STEMI patients, tirofiban prior to transfer for PCI is beneficial

  • Upstream tirofiban reduces ST-elevation post-PCI and nonsignificantly decreases mortality

  • Potential for increased bleeding with upstream tirofiban

>3 mm ST-elevation post-PCI

Mortality

Upstream tirofiban

Provisional tirofiban

Presented by Dr. Christian Hamm at SCAI-ACC i2 Summit/ACC 2008


Periscope l.jpg

PERISCOPE

Least square mean change in % atheroma volume from baseline ↑ 0.73% in the glimepiride arm while it ↓ 0.16% in the pioglitazone arm (p = 0.002)

Composite endpoint: CV death, nonfatal MI, or stroke was similar between the glimepiride (2.2%) and pioglitazone (1.9%) arms (p = 0.78).

CRP, triglycerides ↓, HDL ↑ with pioglitazone

(p = 0.37)

(p = 0.002)

Trial design:Patients with CAD and diabetes were randomized to receive either glimepiride or pioglitazone. Baseline and 18-month IVUS measurements were performed.

Results

0.73

-0.16

0.36

1.1

0.8

1.2

0.6

0.4

0.8

% change in atheroma volume

0.2

Conclusions

%

  • Pioglitazone is better than glimepiride in reducing the progression of CAD in diabetic patients, in the background of optimal medical therapy

  • Pioglitazone has a favorable impact on biochemical parameters, with increased side effects

0.4

0

-0.2

0

Primary endpoint

CV mortality

glimepiride

(n = 273)

Pioglitazone

(n = 270)

Nissen S, et al. JAMA 2008;299:1561-73


Protect pilot l.jpg

PROTECT Pilot

Fewer patients with rolofylline 30 mg experienced >0.3 mg/dl increase in serum creatinine compared with placebo (p < 0.05)

Death or rehospitalization for heart failure: 19% with rolofylline 30 mg and 33% for placebo (p = ns)

No seizures in either group

Trial design:Decompensated heart failure patients were randomized to rolofylline, an adenosine A1 receptor antagonist (30 mg, n = 74; 20 mg, n = 75; 10 mg, n = 74), or placebo (n = 78).

Results

(p = ns)

19

33

%

Conclusions

  • Acute decompensated heart failure patients: less renal dysfunctionwith rolofylline 30 mg

  • Possible reduction in death or rehospitalization for heart failure with rolofylline

Death or rehospitalization for heart failure

Rolofylline

Placebo

Presented by Dr. Barry Massie at the SCAI-ACC i2 Summit/ACC 2008


Reverse l.jpg

REVERSE

Patients worsened: 16% with CRT vs. 21% with optimal medical therapy (p = 0.1)

LV end-systolic volume index: decreased 18.4 ml/m2 vs. 1.3 ml/m2 (p < 0.0001), respectively

Risk of heart failure hospitalization reduced with CRT (p = 0.03)

Trial design:Patients with LV dysfunction (NYHA class I-II) and wide QRS were randomized to cardiac resynchronization therapy (CRT) (n = 419) or optimal medical therapy (n = 191).

Results

(p = 0.1)

16

21

%

Conclusions

  • CRT for mild heart failure does not reduce the percentage of patients that clinically worsen

  • CRT improves LV end-systolic volume index and reduces the risk of hospitalization compared with optimal medical therapy

Percentage worsened

Medical therapy

CRT

Presented Dr. Cecilia Linde at SCAI-ACC i2 Summit/ACC 2008


Seismic l.jpg

SEISMIC

In treatment group, 8.3 years since MI and 31% ejection fraction

Percentage with serious adverse event: 50% in myoblast group and 36% in control (p = ns)

Change in ejection fraction: ↑ 0.3% vs. ↓ 0.1% (p = ns), respectively

Trial design:Patients with myocardial scar were randomized to autologous skeletal myoblast cells (n = 31) or medical therapy (n = 16) and followed for 6 months.

Results

p = ns

p = ns

50

36

+0.3

-0.1

%

%

Serious adverse events

Conclusions

Change in ejection fraction

  • In this small study, implantation of autologous skeletal myoblast cells after MI is feasible

  • No apparent excess in serious adverse events

  • Potential small increase in ejection fraction with myoblast cells at 6 months follow-up

Autologous skeletal myoblast cells

Medical therapy

Presented by Dr. Patrick Serruys at SCAI-ACC i2 Summit/ACC 2008


Spirit ii l.jpg

SPIRIT II

In-stent late loss 0.11 mm (everolimus) and 0.36 mm (paclitaxel) at 6 months (p < 0.001). Similar at 2 years (0.33 mm vs. 0.34 mm, p = 0.61)

MACE at 2 years: 6.6% vs. 11.0% (p = 0.31)

Stent thrombosis at 2 years: 0.9% vs. 1.4% (p = ns)

(p = ns)

(p = 0.61)

Trial design: This was a randomized study designed to evaluate the safety and efficacy of the XIENCE V everolimus-eluting stent compared with the TAXUS paclitaxel-eluting stent among patients with de novo coronary lesions.

Results

0.33

0.34

0.36

1.1

0.5

1.6

0.4

1.2

0.3

Conclusions

%

mm

0.8

  • Benefit in in-stent late lumen loss was seen with everolimus compared with paclitaxel at 6 months, but not seen at 2 years

  • Clinical outcomes were similar to paclitaxel-eluting stents at 2 years

  • Long-term data on stent performance necessary

0.2

0.4

0.1

0

0

In-stent late loss

Stent thrombosis

XIENCE V

(n = 223)

TAXUS

(n = 77)

Presented by Dr. Patrick Serruysat SCAI-ACC i2 Summit/ACC.08


Stradivarius l.jpg

STRADIVARIUS

Percent atheroma volume: +0.25% for rimonabant vs. +0.51% for placebo (p = 0.22)

Psychiatric symptoms: 43% vs. 28% (p < 0.001), respectively

Gastrointestinal track symptoms: 34% vs. 18% (p < 0.001), respectively

Trial design:Obese patients with metabolic syndrome were randomized to the cannabinoid type 1 receptor inhibitor rimonabant 20 mg daily (n = 422) or placebo (n = 417) and underwent IVUS examination after 18 months of treatment.

Results

(p = 0.22)

(p < 0.001)

0.25

0.51

43

28

%

%

Conclusions

  • Rimonabant is not superior to placebo in reducing percent atheroma volume in obese patients with metabolic syndrome

  • Rimonabant results in more psychiatric and gastrointestinal track symptoms compared with placebo

Percent atheroma volume

Psychiatric symptoms

Rimonabant

Placebo

Nissen SE, et al. JAMA 2008;299:1547-60


Tapas l.jpg

TAPAS

Good myocardial blush: 46% with aspiration and 32% with standard PCI (p < 0.001)

ST-segment resolution: 57% and 44%, respectively (p < 0.001)

Death: 2.1% and 4.0%, respectively (p = 0.07)

(p < 0.001)

(p = 0.07)

60

46

32

%

30

4

2.1

0

Good myocardial blush

Mortality

Trial design:Patients with STEMI were randomized to thrombus aspiration prior to PCI (n = 535) or standard PCI without aspiration (n = 536).

Results

Conclusions

  • In STEMI, thrombus aspiration prior to PCI is superior to standard PCI without aspiration

  • Thrombus aspiration improves myocardial blush and ST-segment resolution

  • Thrombus aspiration may improve adverse events including survival

PCI alone

(n = 536)

Thrombus aspiration and PCI (n = 535)

Svilaas T, et al. N Engl J Med 2008;358:557-67


Transfer ami l.jpg

TRANSFER-AMI

Primary endpoint: death, MI, heart failure, severe recurrent ischemia, or shock 10.5% in pharmacoinvasive arm vs. 16.5% in standard treatment arm (p = 0.0013)

Reinfarction: 3.3% vs. 6.0% (p = 0.044)

Recurrent ischemia: 0.2% vs. 2.2% (p = 0.02)

(p = 0.0013)

(p = 0.94)

Pharmacoinvasive arm

(n = 522)

Standard therapy

(n = 508)

Trial design:Patients with STEMI who presented to centers where timely primary PCI was not feasible were randomized to a pharmacoinvasive strategy (emergent transfer for PCI within 6 hours of fibrinolysis) or to standard treatment after fibrinolysis.

Results

20

5

16.5

4

3.7

3.6

%

3

10.5

10

%

2

Conclusions

1

  • Pharmacoinvasive approach safe and efficacious compared with treatment with thrombolytics and transfer for rescue PCI only

  • Optimal window: 6 hours

0

0

Primary endpoint

Mortality

Presented by Dr. Warren Cantor at SCAI-ACC i2 Summit/ACC.08


Victory l.jpg

VICTORY

Years since CABG: 3.9 in rosiglitazone group and 3.7 in placebo group

Saphenous vein graft plaque volume: +0.9% vs. +2.8% (p = 0.22), respectively

Mortality: no deaths in either group

MI: 0 vs. 1, respectively

Trial design:Type 2 diabetic patients with prior CABG were randomized to rosiglitazone (n = 98) or placebo (n = 95) after baseline coronary angiography and IVUS.

Results

(p = 0.22)

0.9

2.8

%

Conclusions

Change in saphenous vein graft plaque volume

  • Rosiglitazone does not change saphenous vein graft plaque volume in type 2 diabetic patients after CABG

  • The incidence of mortality and MI is similar between rosiglitazone and placebo

Rosiglitazone

Placebo

Presented by Dr. Olivier Bertrand at SCAI-ACC i2 Summit/ACC 2008


Vision 302 l.jpg

VISION 302

Binodenoson was noninferior to adenosine. The mean paired summed difference scores difference of binodenoson vs. adenosine images was -0.09 (95% CI -0.44 to 0.27)

2nd or 3rd degree AV block was 0% with binodenoson and 3% with adenosine (p = 0.004)

(p < 0.05)

(p = 0.004)

Trial design: Patients with known or suspected CAD undergoing a pharmacologic stress test with SPECT imaging were stratified and randomized to binodenoson or adenosine for the determination of the magnitude of ischemia.

Results

30

50

0

3

3

50

40

2

30

%

%

Conclusions

20

  • Binodenoson (selective A2A receptor agonist) is as effective as adenosine (nonselective agonist) as agent for detection of ischemia in pharmacologic stress tests in suspected/known CAD patients

  • Side effects are fewer and less intense with binodenoson compared with adenosine

1

10

0

0

2nd or 3rd degree AV block

Flushing

Binodenoson

(n = 402)

Adenosine

(n = 404)

Presented by Dr. James Udelson at SCAI-ACC i2 Summit/ACC 2008


Esc congress 2008 clinical trial summary slides l.jpg

ESC Congress 2008 Clinical Trial Summary Slides


3t 2r l.jpg

3T/2R

Troponin I or T >3x ULN at 48 hours: 20% for tirofiban vs. 35% for placebo (p = 0.009)

MACE at 30 days: 21% vs. 37% (0.006), respectively

TIMI major bleeding at 30 days: 0 vs. 0

Trial design:Patients undergoing PCI were screened for poor response to aspirin and/or clopidogrel. Poor responders were then randomized to tirofiban (n = 132) or placebo (n = 131). Follow-up was 30 days.

Results

(p = 0.009)

(p = 0.006)

37

35

%

20

21

Conclusions

  • Tirofiban is beneficial at reducing MI within 48 hours after PCI among poor responders to aspirin and/or clopidogrel

  • Tirofiban also reduced MACE at 30 days

  • There were no major bleeds in either group

Troponin I or T >3x ULN at 48 hours

MACE at 30 days

Tirofiban

Placebo

Presented by Dr. Marco Valgimigli at ESC 2008


Appraise 1 l.jpg

APPRAISE-1

ISTH major or CRNM bleeding: 7.9% for 10 mg apixaban, 5.7% for 5 mg apixaban, 3% for placebo (p = 0.005 for high-dose vs. placebo and p = 0.09 for low-dose vs. placebo)

Death, MI, recurrent ischemia, or stroke: 6.0%, 7.6%, 8.7% (p = 0.07 for high-dose vs. placebo and p = 0.21 for low-dose vs. placebo), respectively

Trial design:Patients recovering from an ACS were randomized to apixaban 10 mg daily (n = 318), apixaban 2.5 mg twice daily (n = 317), or placebo (n = 611). Study medications were administered for 6 months.

Results

p = 0.005 for high-dose vs. placebo

p = 0.09 for low-dose vs. placebo

7.9

5.7

%

Conclusions

3

  • This dose-finding study reveals that bleeding is increased among patients with a recent ACS with higher doses of apixaban compared with placebo

  • Although this study was not powered for efficacy, adverse events appeared to be lowest with 10 mg apixaban

ISTH major or clinically relevant nonmajor bleeding

Apixaban 5 mg

Apixaban 10 mg

Placebo

Presented by Dr. John Alexander at ESC 2008


Athena l.jpg

ATHENA

Dronedarone associated with a 24% ↓ in cardiac hospitalizations or death vs. placebo (p<0.001)

Overall mortality similar (p = 0.18), cardiovascular mortality lower with dronedarone (p = 0.03)

Higher GI side-effects and increased creatinine with dronedarone, other side-effects similar

(p = 0.18)

(p = 0.027)

Trial design: High-risk patients with paroxysmal or persistent atrial fibrillation or flutter were randomized to dronedarone 400 mg twice daily or placebo. Patients were followed for a mean of 21 months.

Results

10

10

6.0

5.0

Conclusions

5

5

%

  • Dronedarone is safe and effective in the chronic management of atrial fibrillation in high-risk patients

  • Head-to-head comparison with amiodarone awaited

%

1.8

1.2

0

0

Mortality

Stroke

Dronedarone

(n = 2301)

Placebo

(n = 2327)

Presented by Dr. Stefan Hohnloser at the Heart Rhythm Society 2008


Beautiful l.jpg

BEAUTIFUL

Difference in heart rate at 24 months: 5.6 bpm lower with ivabradine

CV death, MI, or HF: 15.4% for ivabradine vs. 15.3% for placebo (p = 0.94)

All-cause mortality:10.4% vs.10.1% (p=0.55)

HF admission: 7.8% vs. 7.9% (p = 0.85)

Trial design:Patients with stable CAD and moderate LV dysfunction were randomized to the sinoatrial node inhibitor, ivabradine (n = 5,479), or placebo (n = 5,438). Median follow-up was 19 months.

Results

(p = 0.94)

(p = 0.55)

15.4

15.3

10.4

10.1

%

Conclusions

  • Ivabradine produces a sustained reduction in heart rate over long-term follow-up

  • Among patients with stable coronary disease and moderate LV dysfunction, ivabradine does not improve mortality, MI, or HF admissions

CV death, MI, HF admission

All-cause mortality

Ivabradine

Placebo

Fox K, et al. Lancet 2008;Aug 31:[Epub before print]


Cardia l.jpg

CARDia

Primary endpoint (death, MI, stroke) was similar between CABG and PCI (10.2% vs. 11.6%, p = 0.63)

Significant ↓ in repeat revascularization in CABG arm (2% vs. 9.9%, p = 0.001). True in drug-eluting stent subset also

Trend toward increased CVA in CABG arm (p = 0.09)

(p = 0.63)

(p = 0.001)

CABG

(n = 254)

PCI

(n = 256)

Trial design: Diabetic patients with multi-vessel disease or complex single-vessel disease, but not left main disease, were randomized to either CABG or PCI. Clinical outcomes were compared at 12 months.

Results

20

20

15

15

11.6

%

%

Conclusions

10.2

9.9

10

10

  • Similar incidence of death, MI, or stroke in diabetics with CABG or PCI

  • CABG was associated with fewer repeat revascularizations compared with PCI

  • No difference in death, MI, but trend toward increased stroke with CABG, as suggested by other studies

5

5

2.0

0

0

Repeat revascularization

Primary endpoint

Presented by Dr. Akhil Kapur at ESC 2008


Caress in ami l.jpg

CARESS-in-AMI

86% of the immediate PCI group underwent PCI vs. 30% of the standard care group

Death, MI, or refractory ischemia at 30 days (4.4% vs. 10.7%, p = 0.005)

Refractory ischemia (0.3% vs. 4.0%, p = 0.003)

Trial design:STEMI patients admitted to non-PCI hospitals and initially treated with heparin, half-dose reteplase, and abciximab were randomized to immediate transfer for urgent PCI (n = 299) or standard therapy with rescue PCI if needed (n = 301).

Results

(p = 0.005)

(p = 0.47)

10.7

%

4.4

3.4

Conclusions

2.3

  • STEMI patients treated with half-dose lytics and abciximab did better with immediate transfer for PCI

  • This approach reduced death, MI, or refractory ischemia at 30 days

  • Benefit driven by reduction in refractory ischemia

MACE

Major bleeding

Transfer for PCI

(n = 299)

Standard therapy

(n = 301)

Di Mario C, et al. Lancet 2008;371:559-68


Decrease iii l.jpg

DECREASE III

Myocardial ischemia was significantly reduced with statin (OR 0.53; 95% CI 0.32-0.88, p = 0.016)

LDL (p < 0.001) and hs-CRP (p  0.001) were lower in statin arm

Incidence of adverse events was similar

(p = 0.016)

(p = 0.039)

Fluvastatin XL

(n = 250)

Placebo

(n = 247)

Trial design: Patients undergoing noncardiac vascular surgery were randomized to fluvastatin XL or placebo, in addition to beta-blockers. Clinical outcomes were compared at 1 month.

Results

19.0

20

20

15

15

Conclusions

10.9

%

%

10.1

10

10

  • Perioperative statin therapy was associated with improved outcomes in high-risk patients undergoing noncardiac vascular surgery

  • Results add to current literature on the benefit of statins in the perioperative period

4.8

5

5

0

0

Myocardial ischemia

CV death or MI

Presented by Dr. Don Poldermans at ESC 2008


Slide40 l.jpg

FIRE

Total late enhancement zone at 5 days: 21.7 g for FX06 vs. 27.3 g for placebo (p = 0.21) and at 4 months: 15.4 g vs. 19.3 g (p = 0.36), respectively

LVEF at 4 months: 49% vs. 49%, respectively

Serious adverse events: 18% vs. 24%, respectively

Trial design:STEMI patients were randomized to the fibrin-derived peptide FX04 400 mg intravenously (n = 114) versus placebo (n = 120).

Results

(p = 0.36)

19.3

15.4

(g)

Conclusions

Total late enhancement zone at 4 months

  • This study failed to meet its endpoint of a reduction in total late enhancement

  • There was no difference in LVEF at follow-up

  • There were no important safety signals with the use of this agent

FX04

Placebo

Presented by Dr. Dan Atar at ESC 2008


Gissi hf n 3 pufa study l.jpg

GISSI-HF: n-3 PUFA Study

No difference between the two arms for primary endpoint (death), but significant difference noted on multivariate analysis (HR 0.91, 95.5% CI 0.83-1.0; p = 0.041)

No difference in the incidence of first admission for heart failure, but fewer admissions for arrhythmia related issues (p = 0.013)

(p = 0.12)

(p = 0.013)

n-3 PUFA

(n = 3,494)

Placebo

(n = 3,481)

Trial design: Patients with symptomatic CHF were randomized to 1 g n-3 PUFA daily or placebo, in addition to optimal medical treatment. Clinical outcomes were compared at 12 months.

Results

29.1

30

20

27.3

15

20

%

%

Conclusions

10

  • No significant difference in mortality in the n-3 PUFA arm, compared with placebo in patients with symptomatic heart failure, on optimal treatment

  • However, multivariate analysis showed n-3 PUFA was associated with small reduction in mortality (absolute RR 1.8%) compared with placebo

  • Exact mechanism is unclear, although reduction in readmission for arrhythmias was noted

10

4.0

5

3.0

0

0

Arrhythmia related hospitalization

Mortality

GISSI-HF Investigators. Lancet 2008;Aug 31:[Epub]


Gissi hf rosuvastatin study l.jpg

GISSI-HF: Rosuvastatin Study

All-cause mortality: 29% with rosuvastatin vs. 28% with placebo (p = 0.94)

Death or hospital admission for cardiovascular reasons: 57% vs. 56% (p = 0.90), respectively

Sudden cardiac death: 9.6% vs. 8.6% (p = 0.26), respectively

Trial design:Patients with chronic symptomatic HF were randomized to rosuvastatin 10 mg daily (n = 2,285) or placebo (n = 2,289). Median follow-up, 3.9 years.

Results

(p = 0.94)

(p = 0.90)

57

56

%

29

28

Conclusions

All-cause mortality

Death or hospital admission for CV reasons

  • Rosuvastatin 10 mg daily is not beneficial at reducing cardiac outcomes among patients with chronic symptomatic HF

  • This study should not temper enthusiasm for statins in indicated situations like ACS

Rosuvastatin

Placebo

GISSI-HF Investigators. Lancet 2008;Aug 31:[Epub]


Ibis 2 l.jpg

IBIS-2

Lp-PLA2 reduced 59% by darapladib (p < 0.001)

Plaque deformability: similar between the groups at follow-up (p = 0.22)

Necrotic core volume: -0.5 mm3 with darapladib (p = 0.71); +4.5 mm3 with placebo (p = 0.009)

MACE: 17% vs. 19% (p = ns), respectively

Trial design:Patients with CAD were randomized to darapladib 160 mg daily (n = 175) vs. placebo (n = 155). Patients underwent IVUS of a nonintervened segment at baseline and at 12 months.

Results

p = 0.71, change with darapladib

p = 0.009, change with placebo

4.5

mm3

Conclusions

-0.5

  • Treatment with the Lp-PLA2 inhibitor darapladib does not affect plaque deformability

  • Darapladib appears to stabilize the necrotic lipid core

  • Similar adverse events between the groups

Change in necrotic core volume at follow-up

Darapladib

Placebo

Serruys PW, et al. Circulation 2008;Sep 1:[Epub]


Leaders l.jpg

LEADERS

Successful stent implantation: 97.5% for biolimus vs. 95.7% for sirolimus (p = 0.05)

Death, MI, or TVR: 9.2% vs. 10.5% (p = 0.003 for non-inferiority), respectively

Stent thrombosis: 1.9% vs. 2.0% (p = 0.84), respectively

Trial design:Patients with stable coronary disease or ACS were randomized to the biolimus-eluting stent with a biodegradable polymer (n = 857) or the sirolimus-eluting stent with a durable polymer (n = 850). Follow-up was for 9 months.

Results

(p = 0.003 for non-inferiority)

(p = 0.84)

10.5

9.2

%

Conclusions

2.0

1.9

  • Biolimus-eluting stent is non-inferior to sirolimus-eluting stent for death, MI, or TVR

  • Higher rate of successful implantation with the biolimus-eluting stent

  • Theoretically, a biodegradable polymer could decrease late stent thrombosis; however, longer-term follow-up is needed

Stent thrombosis

Death, MI, urgent revascularization

Biolimus-eluting stent

Sirolimus-eluting stent

Windecker S, et al. Lancet 2008;Sept 1:[Epub before print].


Pihrate l.jpg

PIHRATE

ST-resolution at 60 minutes: 50% with thrombectomy vs. 41% with primary PCI (p = 0.28)

Myocardial blush grade of 3: 76% vs. 59% (p = 0.023), respectively

6-month mortality: 4.0% vs. 3.1% (p = 0.74), respectively

Trial design:Patients with STEMI were randomized to aspiration thrombectomy plus PCI (n = 102) versus primary PCI alone (n = 94). Follow-up was 6 months.

Results

(p = 0.28)

(p = 0.74)

50

4.0

41

%

%

3.1

Conclusions

ST-segment resolution at 60 minutes

6-month mortality

  • Among STEMI patients, a strategy of aspiration thrombectomy compared with primary PCI failed to improve ST-resolution after PCI, although it did enhance myocardial blush grade of 3

  • Mortality was similar between the groups

Aspiration thrombectomy

Primary PCI

Presented by Dr. Dariusz Dudek at ESC 2008


Regent l.jpg

REGENT

EF change: +3% selected cells (p = 0.04), +3% unselected cells (p = 0.01), 0% control (p = 0.73) (p = ns between groups)

Death: 1.3%, vs. 1.3%, vs. 2.5% (p = 0.92), respectively

Myocardial infarction: 5.0%, vs. 1.3%, vs. 5.0% (p = 0.61), respectively

Trial design:Patients with acute MI and LV dysfunction (EF ≤40%) were randomized to selected CD34+ CXCR4+ bone marrow cells (n = 80), unselected bone marrow cells (n = 80), or control (n = 40). Follow-up was 6 months.

Results

p = ns for stem cell LVEF change compared with control

3

3

20

35

37

21

%

0

Conclusions

  • In patients with acute MI and LV dysfunction, both selected and unselected bone marrow derived stem cells minimally increased LVEF at 6 months

  • This did not translate into a difference in LVEF at follow-up between the groups

  • Similar adverse events between the groups

Change in LVEF at 6 months

Unselected stem cells

Selected stem cells

Control

Presented by Dr. Michal Tendera at ESC 2008


Reverse47 l.jpg

REVERSE

Patients worsened: 16% with CRT vs. 21% with optimal medical therapy (p = 0.1)

LV end-systolic volume index: decreased 18.4 ml/m2 vs. 1.3 ml/m2 (p < 0.0001), respectively

Risk of heart failure hospitalization reduced with CRT (p = 0.03)

Trial design:Patients with LV dysfunction (NYHA class I-II) and wide QRS were randomized to cardiac resynchronization therapy (CRT) (n = 419) or optimal medical therapy (n = 191).

Results

(p = 0.1)

16

21

%

Conclusions

  • CRT for mild heart failure does not reduce the percentage of patients that clinically worsen

  • CRT improves LV end-systolic volume index and reduces the risk of hospitalization compared with optimal medical therapy

Percentage worsened

Medical therapy

CRT

Presented Dr. Cecilia Linde at SCAI-ACC i2 Summit/ACC 2008


Slide48 l.jpg

61% ↓ in LDL in ezetimibe/simvastatin arm

No difference in the composite endpoint between the two groups (HR 0.96, 95% CI 0.83-1.12)

Increased incidence of cancer (9.9% vs. 7.0%, p = 0.03) and cancer deaths (4.1% vs. 2.5%, p = 0.05) with ezetimibe/simvastatin

SEAS

(p = NS)

(p = 0.05)

Ezetimibe/ Simvastatin

(n = 943)

Placebo

(n = 930)

Trial design:Patients with asymptomatic mild to moderate calcific AS were randomized to treatment with ezetimibe/simvastatin 10/40 mg or placebo. Cardiovascular outcomes over 4 years were compared.

Results

5

38.2

40

35.3

4.1

4

30

3

2.5

%

%

20

Conclusions

2

  • No benefit with ezetimibe/simvastatin in asymptomatic AS patients other than a reduction in atherosclerotic events

  • Final full publication is awaited

10

1

0

0

Composite endpoint

Deaths from cancer

Pedersen TR. Press release July 21, 2008


Syntax l.jpg

SYNTAX

MACCE was significantly lower in CABG arm compared with PCI (12.1% vs. 17.8%, p = 0.0015), especially for diabetics (p = 0.0025)

Significant ↓ in the need for repeat revascularization in CABG arm (p = 0.0001)

Death and MI were similar; CVA ↑ with CABG (p = 0.003)

(p = 0.0015)

(p = 0.0001)

CABG

(n = 897)

DES-PCI

(n = 903)

Trial design:Patients with severe three-vessel disease or left main (LM) disease were randomized to either CABG or DES-PCI with paclitaxel-eluting stents. Clinical outcomes were compared at 12 months.

Results

20

20

17.8

13.7

15

15

12.1

%

%

Conclusions

10

10

5.9

  • CABG was associated with fewer repeat revascularizations compared with DES-PCI in patients with LM or three-vessel disease, but a higher rate of stroke

  • No difference in death, MI, or thrombosis

  • Diabetics are especially more likely to benefit with CABG compared with DES-PCI

5

5

0

0

MACCE

Repeat revascularization

Presented by Dr. Patrick Serruys at ESC 2008


Syntax registry l.jpg

Main reason for PCI only: inoperable (comorbidities); main reason for CABG only: complex anatomy

PCI outcomes: MACCE (20.4%), mortality (7.3%), MI (4.2%), repeat revascularization (12%), CVA (0)

CABG outcomes: MACCE (8.8%), mortality (2.5%), MI (2.5%), repeat revascularization (3%), CVA (2.2%)

SYNTAX Registry

Trial design:Patients with severe three-vessel or left main (LM) disease who did not meet criteria for entry into the SYNTAX trial were followed for 12 months in the SYNTAX CABG and PCI registry.

Results

25

25

20

20.4

20

20

15

%

%

15

Conclusions

12.0

8.8

10

10

10

  • The SYNTAX registry describes outcomes in PCI and CABG in patients not eligible for the SYNTAX trial

  • Of all-comers with three-vessel and/or LM disease, 6.4% were considered inoperable; 35% not feasible for PCI

5

3.0

5

0

0

CABG

(n = 1,077)

DES-PCI (n = 198)

Repeat revascularization

MACCE

Presented by Dr. Friedrich Mohr at ESC 2008


Time chf l.jpg

No difference in final NT-BNP between the 2 arms

No difference in the survival (p = 0.06) or hospitalization-free survival (p = 0.46), but ↓ in CHF hospitalization-free survival (p = 0.008)

Greater reductions in patients younger than 75 years

Quality of life better in older patients with standard therapy

TIME-CHF

(p < 0.05)

Trial design:Patients with chronic systolic HF were randomized to intensified BNP-guided therapy or standard therapy, with the specific inclusion of patients ≥75 years. Clinical outcomes were compared at 18 months.

Results

20

15

10

%

6.0

5

Conclusions

2.0

  • Intensified BNP-guided therapy was not associated with better survival

  • Elderly patients do better with standard therapy, including in quality-of-life assessment

0

Change in quality of life,

Age ≥75 years

Standard therapy

(n = 248)

Intensified therapy

(n = 251)

Presented by Dr. H.P. Brunner-La Roccaat ESC 2008


Timic l.jpg

TIMIC

Majority in immunosuppressive therapy arm showed an ↑ in LVEF (26.4-48.0%) and ↓ in LV end-diastolic diameter (LVEDD) (68.6-52.8 mm)

None of the patients in the placebo arm improved; some showed further ↓ in LVEF and ↑ in LVEDD

(p < 0.05)

Trial design: Patients with virus-negative inflammatory cardiomyopathy were randomized to either immunosuppressive therapy with prednisone and azathioprine or placebo for 6 months. Echocardiographic parameters were compared at 6 months.

Results

30

21.6

15

Conclusions

  • Immunosuppressive therapy in virus-negative inflammatory cardiomyopathy may be associated with an improvement in LVEF and LVEDD, compared with placebo

  • Clinical outcomes are awaited

  • May represent novel approach to heart failure management in these patients

%

0

-8.1

-15

Change in LVEF from baseline

Immunosuppressive therapy

(n = 43)

Placebo

(n = 42)

Presented by Dr. Andrea Frustaci at ESC 2008


Transcend l.jpg

TRANSCEND

No difference between telmisartan (15.7%) and placebo (17.0%) in the incidence of the primary outcome (CV death, MI, stroke, CHF) (p = 0.22)

Stroke, death, or MI was reduced with telmisartan (p = 0.05)

No difference in mortality (p = 0.49); marginal reduction in MI (3.9% vs. 5.0%, p = 0.06)

(p = 0.22)

(p = 0.49)

Trial design:Patients at high risk for cardiovascular events, and with intolerance to ACE inhibitors, were randomized to telmisartan or placebo. Patients were followed for a median of 56 months.

Results

15

20

17.0

12.3

15.7

11.7

%

10

10

%

5

Conclusions

  • Telmisartan is not more effective than placebo in reducing the incidence of the composite primary endpoint, but does reduce the incidence of stroke, death, or MI

  • May be an alternative in high-risk patients, who are intolerant to ACE inhibitors

0

0

Primary endpoint

Mortality

Telmisartan

(n = 2,954)

Placebo

(n = 2,972)

TRANSCEND Investigators. Lancet 2008;Aug 31:[Epub]


Tct 2008 clinical trial summary slides l.jpg

TCT 2008 Clinical Trial Summary Slides


Bbc one l.jpg

BBC ONE

MACE (death, MI, or TVF) was more frequent in the complex strategy arm (HR 2.0, 95% CI 1.2-3.5, p = 0.009), as well as MI (p = 0.001)

Incidence of mortality, TVF, and stent thrombosis was similar between the two arms (p > 0.05)

TIMI major bleeding was higher with the complex strategy (1.2% vs. 0.4%, p > 0.05)

(p = 0.009)

(p > 0.05)

Simple strategy

(n = 250)

Complex strategy

(n = 250)

Trial design: Patients with bifurcation lesions were randomized to either a simple stepwise provisional T-stent strategy or a complex strategy involving either crush or culotte techniques. Clinical outcomes were compared at 9 months.

Results

20

20

15.2

15

15

%

%

10

10

8.0

Conclusions

5

5

  • A simple stepwise T-stent strategy is superior to a more complex strategy involving crush or culotte techniques in patients with bifurcation lesions

2.0

0.4

0

0

MACE

Stent thrombosis

Presented by Dr. David J. Hildick-Smith at TCT 2008


Cool rcn l.jpg

COOL RCN

No difference in incidence of contrast-induced nephropathy (CIN) between hypothermic and normothermic groups (OR 1.27, 95% CI 0.53-3.00, p = 0.59)

No difference in serum creatinine at 24 hours (p = 0.30) and 48 hours (p = 0.09) post-procedure

All-cause mortality was similar (p = 0.22)

(p = 0.59)

(p = 0.22)

Routine management

(n = 73)

Hypothermia

(n = 63)

Trial design: Patients with pre-existing renal dysfunction undergoing cardiac catheterization were randomized to systemic hypothermia (core temperature 33-340C) or routine management. Clinical outcomes were compared at 30 days.

Results

100

20

80

15

60

%

%

10

40

Conclusions

5.2

22.4

5

20

18.6

1.4

  • Systemic hypothermia is not superior to routine hydration in patients with pre-existing renal dysfunction undergoing cardiac catheterization

0

0

CIN

Mortality

Presented by Dr. Gregg Stone at TCT 2008


Endeavor iv l.jpg

ENDEAVOR IV

MACE was similar between the two arms (p = 0.93)

Incidence of non-Q-wave MI was lower in the ZES arm (p = 0.022), whereas target vessel failure was similar between the two arms (p = 0.23)

Overall rates of stent thrombosis similar (p = 1.0)

(p = 0.93)

(p = 1.0)

PES

(n = 775)

ZES

(n = 773)

Trial design: ENDEAVOR IV was a randomized trial of the Endeavor zotarolimus-eluting stent (ZES) vs. the Taxus paclitaxel-eluting stent (PES) in patients undergoing PCI for single de novo coronary lesions. Clinical outcomes were compared at 2 years.

Results

20

20

15

15

%

%

10.0

Conclusions

9.8

10

10

  • Among patients undergoing PCI for single de novo lesions, use of ZES was associated with a similar incidence of MACE, target vessel failure, and stent thrombosis compared with PES at 2 years

  • Lower rate of non-Q-wave MI noted with ZES compared with PES needs to be corroborated by other studies

5

5

1.1

0.9

0

0

MACE

Stent thrombosis

Presented by Dr. Martin Leon at TCT 2008


Slide58 l.jpg

FAME

Resource utilization (contrast: 272 vs. 302 ml, cost of procedure ($5,332 vs. $6,007) shorter with FFR-guided PCI compared with routine PCI (all p < 0.05)

MACE lower at 1 year with FFR (p = 0.02)

Incidence of death (p = 0.19), MI (p = 0.07), and CABG or re-PCI (p = 0.08) at 1 year were similar

(p = 0.02)

(p = 0.19)

Routine PCI

(n = 496)

FFR-guided PCI

(n = 509)

Trial design: Patients with multivessel disease were randomized to either routine angiography-guided PCI or fractional flow reserve (FFR)-guided PCI, with stenting of only those lesions with an FFR of ≤0.8. Clinical outcomes were compared at 1 year.

Results

20

18.4

20

15

15

13.2

%

%

10

10

Conclusions

  • FFR-guided PCI is associated with a lower incidence of MACE compared with angiography-guided PCI in patients with multivessel disease, with a decrease in resource utilization

  • Further studies validating these findings are necessary

5

5

3.0

1.8

0

0

MACE

Death

Presented by Dr. Nico Pijls at TCT 2008


Horizons ami l.jpg

HORIZONS-AMI

Unfractionated heparin was used prior to randomization in 66% of patients

Death, MI, TVR, stroke, or bleeding: 9.2% for bivalirudin vs. 12.1% for heparin + GP IIb/IIIa inhibitor (p = 0.005)

Major bleeding: 4.9% vs. 8.3% (p < 0.001), respectively

Trial design:STEMI patients undergoing primary PCI were randomized to bivalirudin (n = 1,800) or heparin plus a glycoprotein (GP) IIb/IIIa inhibitor (n = 1,802). The investigator was not blinded to treatment assignment. Patients were followed for 30 days.

Results

(p = 0.005)

(p < 0.001)

9.2

12.1

4.9

8.3

%

Conclusions

  • During primary PCI, bivalirudin alone is superior to heparin plus a GP IIb/IIIa inhibitor

  • Bivalirudin alone reduces the composite of death, myocardial infarction, target vessel revascularization, stroke, or bleeding

  • Improvement in the primary outcome was driven by a reduction in major bleeding

Death, MI, TVR, stroke, or bleeding

Major bleeding

Heparin + GP IIb/IIIa inhibitor

Bivalirudin alone

Stone GW, et al. N Engl J Med 2008;358:2218-30


Horizons ami stent l.jpg

HORIZONS-AMI Stent

Significant ↓ in ischemia-driven target lesion revascularization (TLR) in the PES arm (4.5% vs. 7.5%, HR 0.59, 95% CI 0.43-0.83, p = 0.002)

PES non-inferior to BMS in the incidence of MACE (p for non-inferiority = 0.01)

Mortality (p = 0.98), stent thrombosis (p = 0.72), and MI (p = 0.31) similar between the two arms; angiographic restenosis lower with PES (p < 0.0001)

(p = 0.01)*

(p = 0.72)

SES

(n = 749)

PES

(n = 2,257)

Trial design: Patients presenting within 12 hours with a STEMI were randomized in a 3:1 fashion to receive either paclitaxel-eluting (PES) or bare-metal stents (BMS). Clinical outcomes were compared at 9 months.

Results

20

20

15

15

%

%

10

10

8.1

8.0

5

5

3.4

3.1

Conclusions

0

  • PES superior to BMS in reducing restenosis and TLR at 1 year in patients with STEMI

  • Mortality, stent thrombosis, MACE rates similar

0

MACE

Stent thrombosis

* For non-inferiority

Presented by Dr. Gregg Stone at TCT 2008


Isar left main l.jpg

ISAR-Left Main

PES non-inferior to SES in the incidence of MACE (RR 0.85, 95% CI 0.56-1.29; pnon-inferiority < 0.001)

Incidence of death, MI, stroke, and repeat revascularization similar between the two arms (all p > 0.05)

Stent thrombosis similar in both arms (0.3% vs. 1.0%, p > 0.05) at 2 years

(p < 0.001)*

(p > 0.05)

SES

(n = 305)

PES

(n = 302)

Trial design: Patients undergoing left main (LM) stenting were randomized to receive either paclitaxel-eluting (PES) or sirolimus-eluting stents (SES). Clinical outcomes were compared at 1 year.

Results

20

20

15.8

15

13.6

15

%

%

10

10

Conclusions

5

5

  • PES non-inferior to SES for the incidence of MACE at 1 year for unprotected LM stenting

  • Rates of stent thrombosis similar up to 2 years of follow-up

1.0

0.3

0

0

MACE

Stent thrombosis

* For non-inferiority

Presented by Dr. Julinda Mehili at TCT 2008


Isar test 2 l.jpg

ISAR-TEST-2

Angiographic restenosis similar between dual-DES (11.0%) and SES (12.0%) (p = 0.68), but higher with ZES (19.3%) (p = 0.002) (p = 0.003 overall)

Target lesion revascularization (TLR) similar between dual-DES (6.8%) and SES (7.2%) (p = 0.83), but higher with ZES (13.6%) (p = 0.001)

Incidence of MI (p = 0.8) and stent thrombosis (p = 0.87) similar between the three arms

(p = 0.87)

(p = 0.003)

SES

(n = 335)

Dual-DES

(n = 333)

Trial design: Patients undergoing PCI were randomized in a 1:1:1 fashion to either dual DES (probucol + rapamycin), sirolimus-eluting (SES), or zotarolimus-eluting stents (ZES). Clinical outcomes were compared at 1 year.

Results

19.3

20

20

15

15

12.0

11.0

%

%

10

10

Conclusions

5

5

  • Dual-DES associated with a similar incidence of angiographic restenosis and TLR compared with SES, but lower than ZES

  • Incidence of MI and stent thrombosis similar at 1 year

0.9

0.9

0.6

0

0

Angiographic restenosis

Stent thrombosis

ZES

(n = 339)

Presented by Dr. Robert Byrne at TCT 2008


Odessa l.jpg

ODESSA

Incidence of uncovered/malapposed struts was highest with SES, and lowest with ZES for both overlapping and non-overlapping stents (p < 0.05)

% intimal hyperplasia was lowest with SES and highest with BMS (p < 0.05)

Clinical outcomes at 6 months were similar

(p < 0.05)

(p < 0.05)

Trial design: ODESSA assessed the utility of optical coherence tomography (OCT) in evaluating strut coverage and malapposition of sirolimus-eluting (SES) vs. paclitaxel-eluting (PES) vs. zotarolimus-eluting (ZES) vs. bare-metal stents (BMS) in vivo.

Results

100

20

80

57.8

60

%

%

45.2

8.7

10

8.3

40

Conclusions

31.5

19.3

20

  • Inverse relationship between incidence of uncovered/malapposed struts, and % intimal hyperplasia

  • OCT findings are interesting, but clinical significance and overall utility are unclear

1.8

0.05

0

0

Uncovered/malapposed struts (overlapping stents)

% intimal hyperplasia

SES

n = 22

PES

n = 22

ZES

n = 22

BMS

n = 11

Presented by Dr. Giulio Guagliumi at TCT 2008


Prepare l.jpg

PREPARE

Incidence of >70% ST-resolution (STR) was higher with the Proxis device in the immediate post-procedure period (p = 0.009), but not thereafter

Post-PCI TIMI grade 3 flow (p = 0.06), myocardial blush grade 3 (p = 0.93) were similar between the two arms

MACE, mortality, MI, and stroke similar at 30 days

(p = 0.009)

(p > 0.05)

PCI alone

(n = 143)

Proxis + PCI

(n = 141)

Trial design: Patients presenting within 6 hours with a STEMI were randomized to either PCI with a Proxis (thrombus aspiration + embolic protection) device or routine PCI. Clinical outcomes were compared at 30 days.

Results

100

20

80

15

66.0

60

%

50.0

%

10

7.0

40

Conclusions

4.0

5

  • Proxis device was associated with a higher incidence of >70% STR than routine PCI only in the post-PCI period

  • No impact on TIMI grade 3 flow or clinical outcomes

20

0

0

>70% STR post-PCI

MACE

Presented by Dr. Karel Koch at TCT 2008


Sort out iii l.jpg

SORT-OUT III

MI (p = 0.03), definite stent thrombosis (p = 0.02), target lesion revascularization (p < 0.0001), and clinically significant restenosis (p < 0.0001) were all more frequent with ZES compared with SES

Overall mortality was similar (p = 0.27)

(p = 0.02)

SES

(n = 1,171)

ZES

(n = 1,162)

Trial design: SORT-OUT III was a randomized trial of the Endeavor zotarolimus-eluting stent (ZES) vs. the sirolimus-eluting stent (SES) in patients undergoing PCI. Clinical outcomes were compared at 9 months.

Results

20

15

%

10

Conclusions

  • ZES associated with worse outcomes, including stent thrombosis, compared with SES at 9 months

  • Long-term follow-up data are awaited

  • Similar to other trials showing higher restenosis with ZES; further investigation is required

5

1.2

0.2

0

Stent thrombosis

Presented by Dr. Jens Flensted Lassen at TCT 2008


Zest ami l.jpg

ZEST-AMI

No difference in MACE (p = 0.83), ischemia-driven TVR (p = 0.74), stent thrombosis (p = 0.17), MI (p = 0.11), or death (p = 0.14) between the three groups

In-stent restenosis was lowest with SES (1.4%) compared with ZES (15.9%) and PES (9.6%) at 8 months (p = 0.009)

(p = 0.17)

(p = 0.83)

SES

(n = 110)

ZES

(n = 108)

Trial design: Patients undergoing primary PCI for STEMI were randomized in a 1:1:1 fashion to either zotarolimus-eluting (ZES), sirolimus-eluting (SES), or paclitaxel-eluting stents (PES). Clinical outcomes were compared at 1 year.

Results

20

20

15

15

11.1

%

%

9.1

9.1

10

10

Conclusions

5

3.6

5

  • No difference in clinical outcomes between ZES, SES, and PES, but SES are associated with the lowest incidence of in-stent restenosis, when used in patients with STEMI

2.7

0

0

0

MACE

Stent thrombosis

PES

(n = 110)

Presented by Dr. Cheol-Hwan Lee at TCT 2008


Aha 2008 clinical trial summary slides l.jpg

AHA 2008 Clinical Trial Summary Slides


Approach l.jpg

APPROACH

Change in percent atheroma volume: -0.21% with rosiglitazone vs. 0.43% with glipizide (p = 0.12)

Change in total atheroma volume: -3.9 mm3 vs. 1.2 mm3 (p = 0.04), respectively

Death: 2.4% vs. 2.1%, respectively

Myocardial infarction: 2.1% vs. 1.8%, respectively

Trial design: Diabetic patients were randomized to rosiglitazone titrated to 8 mg daily (n = 333) vs. glipizide titrated to 15 mg daily (n = 339). IVUS was performed at baseline and 18 months.

Results

(p = 0.12)

0.43

%

-0.21

Conclusions

  • Among type 2 diabetic patients, the use of rosiglitazone does not reduce percent atheroma volume compared with glipizide

  • There was a reduction in total atheroma volume with rosiglitazone

  • CV outcomes were similar between groups

Change in percent atheroma volume

Rosiglitazone

Glipizide

Presented by Dr. Richard Nesto at AHA 2008


Atlas timi 46 l.jpg

ATLAS TIMI 46

No difference between rivaroxaban and placebo in the primary outcome (death, MI, stroke, severe ischemia) (HR 0.79, 95% CI 0.60-1.05, p = 0.10)

↓ in death, MI, stroke with rivaroxaban (p = 0.028)

Dose-response curve for bleeding with rivaroxaban, especially in the setting of dual antiplatelet therapy (p < 0.001)

(p = 0.10)

(p = 0.028)

Placebo

(n = 1,160)

Rivaroxaban

(n = 1,166)

Trial design: Patients with ACS were randomized to either rivaroxaban twice daily, once daily, or placebo. Clinical outcomes were compared at 6 months.

Results

20

20

15

15

%

%

10

10

7.0

Conclusions

5.6

5.5

5

3.9

5

  • Rivaroxaban has reasonable efficacy compared with placebo in patients with ACS, with a higher bleeding risk

  • ATLAS TIMI 46 was a phase II clinical trial conducted to identify safe and effective doses of rivaroxaban to be used in the phase III trial

0

0

Primary outcome

Death/MI/Stroke

Presented by Dr. C. Michael Gibson at AHA 2008


Slide70 l.jpg

BACH

In the group admitted with CHF, MR-proADM was associated with a higher prognostic efficacy than both BNP and NT-proBNP (p < 0.001 for both)

Log MR-proADM was associated with a significant improvement in prognostic ability for 90-day mortality in the multivariate model (p < 0.001)

(p < 0.001)

BNP

MR-proADM

Trial design: BACH was a biomarker trial, which compared the prognostic accuracy of mid regional pro-Adrenomedullin (MR-proADM), BNP, and NT-proBNP for 90-day mortality in patients presenting to the emergency room with shortness of breath.

Results

100

73.5

63.6

60.8

50

%

Conclusions

  • The diagnostic ability of MR-proADM for CHF is unclear

  • Clinical utility of these findings is limited

0

Prognostic accuracy in CHF patients

NT-proBNP

Presented by Dr. Stefan Anker at AHA 2008


Slide71 l.jpg

BICC

Viral load reduction or elimination was better in IFNB-1b groups compared with placebo (p = 0.048)

NYHA class was similar at 24 weeks (p = 0.073), quality of life was better in IFNB-1b group (p = 0.032)

No change in echo or hemodynamic parameters

Serious adverse events were similar (p > 0.05)

(p = 0.048)

Placebo

(n = 48)

IFNB-1b

(n = 95)

Trial design: Patients with CVC were randomized to either high-dose (8 million IU), low-dose (4 million IU) IFNB-1b, or placebo. Outcomes were compared at 24 weeks.

Results

40

32

%

20

17

Conclusions

  • IFNB-1b was associated with a nearly twofold increase in viral load reduction or elimination compared with placebo in patients with CVC

  • Results of phase III trial are awaited

0

Viral load reduction or elimination

Presented by Dr. Heinz Peter Schultheiss at AHA 2008


Fit heart l.jpg

FIT Heart

Percent change in LDL: -1.0% for special intervention vs. -2.0% for control (p = NS)

HDL at follow-up: 58.7 mg/dl vs. 57.6 mg/dl (p = 0.01), respectively

BMI at follow-up: 27.7 kg/m2 vs. 28.4 kg/m2 (p = 0.88), respectively

Trial design: Family members of a hospitalized cardiac patient were randomized to a special intervention program for risk factor modification (n = 250) vs control (n = 251). Follow-up was 1 year.

Results

Percent change in LDL cholesterol

%

-1.0

Conclusions

  • Among family members of a hospitalized cardiac patient, a special intervention program is not more effective than a control program in lowering LDL cholesterol

  • Special intervention was associated with a slightly higher HDL, although similar BMI at follow-up

-2.0

(p = NS)

Special intervention program

Control

Mosca L, et al. Circ Cardiovasc Qual Outcomes 2008;1:98-106


Hf action l.jpg

HF-ACTION

No difference in mortality/hospitalizations between the two arms (HR 0.93, 95% CI 0.84-1.02, p = 0.13). On adjustment for other prognostic factors, was ↓ in exercise training arm (p = 0.03)

CV mortality & CV hospitalizations (p = 0.14), 6-minute walk distance (p = 0.26) similar, but peak VO2 higher in the exercise training arm

Serious side effects similar between the two arms

(p = 0.26)

(p < 0.0001)

Usual care

(n = 1,172)

Exercise training

(n = 1,159)

Trial design: Patients with symptomatic systolic CHF on optimal medical therapy were randomized to either exercise training or usual medical care. Clinical outcomes were compared at 3 years.

Results

1.0

20

15

0.7

13

12

m

10

0.5

ml/min/kg

Conclusions

5

  • Prescribed exercise training program in patients with systolic CHF safe and effective, when added on to optimal medical therapy

  • Strengthens current recommendations for exercise in CHF patients

0.1

0

0

Change in 6-minute walk distance

Change in Peak VO2

Presented by Dr. David Whellan at AHA 2008


Hf action substudy l.jpg

HF-ACTION Substudy

Kansas City Cardiomyopathy Questionnaire score at follow-up: +5 points in the exercise group vs. +2 points in the usual care group (p = 0.001)

Clinical improvement: 53% of the exercise group vs. 33% of the usual care group (p < 0.001)

Trial design: Patients with CHF (NYHA II-IV) were randomized to an aerobic exercise training program (n = 1,159) vs. usual care (n = 1,172). Median follow-up was 2.5 years.

Results

(p = 0.001)

5

Points

2

Conclusions

  • Among patients with CHF due to LV systolic dysfunction, participation in an exercise program modestly improves health status compared with usual care

  • This benefit is seen early, within the first 3 months

Change in Kansas City Cardiomyopathy Questionnaire at follow-up

Exercise group

Usual care

Presented by Dr. Kathryn Flynn at AHA 2008


I preserve l.jpg

I-PRESERVE

No difference between irbesartan and placebo arms in the primary outcome (death/CV hospitalization) (HR 0.95, 95% CI 0.86-1.05, p = 0.35)

Incidence of mortality (p = 0.98), worsening CHF (p > 0.05), change in NT-proBNP (p = 0.14) similar

Most side effects similar, except ↑ risk of serious hyperkalemia with irbesartan (3% vs. 2%, p = 0.01)

(p = 0.98)

(p = 0.35)

Placebo

(n = 2,061)

Irbesartan

(n = 2,067)

Trial design: Patients with heart failure and preserved ejection fraction (EF) were randomized to either irbesartan or placebo. Clinical outcomes were compared at 5 years.

Results

100

20

15

%

%

10.7

10.7

50

10

37.0

36.0

Conclusions

5

  • Irbesartan was not associated with a reduction in CV mortality and morbidity in patients with heart failure and preserved EF

  • Results were similar to those for candesartan and perindopril

0

0

Primary outcome

Mortality

Massie BM, et al. N Engl J Med 2008;Nov 11:[Epub]

Presented by Dr. Peter Carson at AHA 2008


Slide76 l.jpg

JPAD

No difference between aspirin and nonaspirin group in the total atherosclerotic events (HR 0.80, 95% CI 0.58-1.10, p = 0.16)

Significant ↓ in fatal coronary and cerebrovascular events (p = 0.0037)

No difference in nonfatal MI (p = 0.5), hemorrhagic strokes (p = 0.48), mortality (p = 0.67)

↑ bleeding with aspirin, not statistically significant

(p = 0.16)

(p = 0.67)

No aspirin

(n = 1,277)

Aspirin

(n = 1,262)

Trial design: Patients with type 2 diabetes and no prior coronary artery disease were randomized in an open-label fashion to either aspirin 81 or 100 mg daily or no aspirin. Clinical outcomes were compared at 5 years.

Results

20

20

15

15

%

%

10

10

6.7

Conclusions

5.4

5

5

3.0

2.7

  • Findings suggest no reduction in total atherosclerotic events, but reduction in total coronary and cerebrovascular events with aspirin in diabetic patients

  • Findings need to be validated by other studies

0

0

Atherosclerotic events

Mortality

Ogawa H, et al. JAMA 2008;300:2134-41

Presented by Dr. Hisao Ogawa at AHA 2008


Jupiter l.jpg

JUPITER

Rosuvastatin associated with a significant ↓ in the primary outcome of MI, stroke, unstable angina, revascularization, or cardiovascular death (HR 0.56, 95% CI 0.46-0.69, p < 0.00001)

All-cause mortality ↓ with rosuvastatin (p = 0.02)

Serious adverse effects were similar (p = 0.60)

(p = 0.02)

(p < 0.00001)

Placebo

(n = 8,901)

Rosuvastatin

(n = 8,901)

Trial design: Apparently healthy patients with LDL cholesterol <130 mg/dl and hs-CRP ≥2 mg/L were randomized to rosuvastatin 20 mg daily or placebo. Clinical outcomes were compared at a median of 1.9 years.

Results

2

2

1.36

1.25

Events/100 person-years

Events/100 person-years

1.0

Conclusions

1

1

0.77

  • Rosuvastatin was associated with a significant reduction in major cardiovascular events, including death, in patients with LDL <130 mg/dl, but high hs-CRP (≥2.0 mg/L)

  • May require revision of current guidelines

0

0

Primary outcome

All-cause mortality

Ridker PM, et al. NEJM 2008;359:2195-207

Presented by Dr. Paul Ridker at AHA 2008


Phs ii l.jpg

PHS II

Neither vitamin C nor vitamin E associated with a reduction in major cardiovascular events compared with placebo (p = 0.86, 0.91, respectively)

No difference in individual outcomes studied

No increase in adverse events, except increased hemorrhagic stroke with vitamin E (p = 0.04)

(p = 0.86)

(p = 0.91)

Vit E

n = 7,315

Vit C

n = 7,329

Placebo

n = 7,326

Placebo

n = 7,312

Trial design: PHS II randomized healthy males in a factorial design to active vitamins E & C, active vitamin E & placebo vitamin C, placebo vitamin E & active vitamin C, & placebo vitamins E and C. Clinical outcomes were compared at 10 years.

Results

20

20

%

10

%

8.5

8.5

8.6

10

8.4

Conclusions

0

  • Vitamins C or E not helpful in the primary prevention of cardiovascular events in healthy patients

  • Confirms earlier studies with vitamin E; one of the first studies with vitamin C

0

Major cardiovascular events

Sesso HD, et al. JAMA 2008;300:2123-33

Presented by Dr. J. Michael Gaziano at AHA 2008


Search l.jpg

SEARCH

No difference in the incidence of major vascular events between high- vs. low-dose simvastatin, or folate + vitamin B12 vs. placebo (p > 0.05 for both)

No difference in individual outcomes studied

↑ risk of myopathy in high-dose vs. low-dose simvastatin arms (0.88% vs. 0.05%, p < 0.05)

(p > 0.05)

(p > 0.05)

Trial design: A 2 x 2 factorial study in which patients with a recent MI were randomized to either simvastatin 80 mg or 20 mg daily, and folic acid + vitamin B12 or placebo. Patients were followed for a mean of 6.7 years.

Results

50

50

%

%

25.7

24.5

25.5

24.8

0

0

Conclusions

Major vascular events

  • Neither high-dose (vs. low-dose) simvastatin nor folate + vitamin B12 (vs. placebo) effective in reducing major vascular events in patients with a recent MI

  • Statin data contrary to other trials on this topic, folate + vitamin B12 data similar

Folate/ Vit B12

n = 6,033

Simvastatin 80 mg

n = 6,031

Simvastatin 20 mg

n = 6,033

Placebo

n = 6,031

Presented by Dr. Rory Collins at AHA 2008


Timacs l.jpg

TIMACS

No difference in primary outcome (death, MI, stroke) between the two arms (HR 0.85, 95% CI 0.68-1.06, p = 0.15), except in high-risk patients (HR 0.65, 95% CI 0.48-0.88, p = 0.005)

Death, MI, refractory ischemia ↓ in early invasive arm (p = 0.0002), due to ↓ in refractory ischemia (p < 0.0001); death (p = 0.81), stroke (p = 0.74) similar

Major bleeding was similar (p = 0.53)

(p = 0.15)

(p = 0.81)

Delayed invasive

(n = 1,438)

Early invasive

(n = 1,593)

Trial design: Patients with NSTEMI were randomized to an early (within 24 hours) or delayed (after 36 hours) invasive strategy. Clinical outcomes were compared at 6 months.

Results

20

20

15

15

11.4

%

%

9.7

10

10

Conclusions

6.0

4.9

5

5

  • An early invasive strategy (within 24 hours) is not associated with harm compared with a delayed invasive strategy (after 36 hours) in patients with NSTEMI, and may be beneficial in high-risk patients

  • Significant reduction in refractory ischemia with an early invasive strategy

0

0

Primary endpoint

Mortality

Presented by Dr. Shamir Mehta at AHA 2008


Thinrs l.jpg

THINRS

Death, stroke, or major bleeding: 7.9% per patient-year for self-testing vs. 8.9% per patient-year for conventional testing (p = 0.1)

Death: 3.4% vs. 3.7%, respectively

Major bleeding: 3.9% vs. 4.5%, respectively

Trial design: Patients who required chronic anticoagulation were randomized to patient self INR testing (n = 1,465) vs conventional monthly INR testing (n = 1,457). Follow-up was 4.5 years.

Results

(p = 0.1)

8.9

7.9

% per patient-year

Conclusions

  • Patient self-testing for INR monitoring does not reduce the composite outcome of death, stroke, or major bleeding

  • No signal for increased adverse events, such as major bleeding, with self-testing

Death, stroke, or major bleeding

Patient self INR testing

Conventional INR testing

Presented by Dr. Alan Jacobson at AHA 2008


Vasp guided pci l.jpg

VASP-Guided PCI

Stent thrombosis more frequent in the routine PCI arm compared with VASP-guided PCI (p = 0.03)

MACE ↓ in the VASP-guided PCI arm (p < 0.001), mainly due to ↓ in MI (p = 0.01). Rates of cardiovascular death, urgent revascularization were similar (p = 0.06 for both)

Bleeding rates were similar (p = 0.8)

(p = 0.03)

(p = 0.06)

Routine PCI

(n = 215)

VASP-guided PCI

(n = 214)

Trial design: Patients undergoing nonemergent PCI, and a VASP index of ≥50% were randomized to either routine management, or VASP-guided further loading doses of clopidogrel until VASP index <50%. Clinical outcomes were compared at 30 days.

Results

20

20

15

15

%

%

10

10

Conclusions

4.7

  • VASP-guided PCI, with an aim to reduce the VASP index below 50%, was associated with better outcomes in patients undergoing nonemergent PCI and VASP index ≥50%

  • Needs to be corroborated by other studies

5

5

1.8

0.5

0

0

0

Stent thrombosis

CV death

Presented by Dr. Frank Paganelli at AHA 2008


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