2008 Clinical Trial 2008 Clinical Trial Summary SlidesSummary Slides

ACC Annual Scientific Session ACC Annual Scientific Session

AHA Scientific Sessions AHA Scientific Sessions

ESC CongressESC Congress

ACC.08/SCAI-ACCi2 ACC.08/SCAI-ACCi2

Clinical Trial Summary SlidesClinical Trial Summary Slides

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)

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

Results

Conclusions

HCTZ/benazapril(n = 5,721)

Amlodipine/benazapril(n = 5,741)

•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

8

12

4

Primary endpoint

11.4 9.2

%

(p = 0.0002)

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

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)

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]

0

4

8

12

MACE T otal bleeding

(p = 0.007) (p = 1.0)

VASP-guided extra

clopidogrel(n = 78)

No extra clopidogrel

(n = 84)

0 9.5

3.9 4.8%

MACE Total bleeding

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

Conclusions

• 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

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

(p = ns) (p = ns)

PCI plus embolic

protection

Standard PCI

In-hospital MACE

TIMI 3 flow post-PCI

%

11.7 9.5

94 94

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

Conclusions

Aliskiren(n = 154)

Losartan(n = 152)

•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

4

6

2

Primary endpoint

4.9 4.8

g/m

2

(p < 0.0001*)

(p = 0.52**)

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

5.8

Combination(n = 154)

* Aliskiren vs. losartan for noninferiority

** Combination vs. losartan

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

Conclusions

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

• Clopidogrel reloading may be of benefit in unstable patients

• Favorable bleeding profile with reloading

(p = 0.70) (p = 0.035)

Presented by Dr. Germano Di Sciascio at SCAI-ACC i2 Summit/ACC 2008

Clopidogrel reload

No reload

MACE in entire study

population

MACE in ACS patients

%

7 9

7 18

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

Conclusions

• 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

(p = ns) (p = ns)

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

Renal stenting

Medical therapy

%

Cardiovascular mortality

Hospitalization for fluid overload or

heart failure

7.4 8.212 14

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)

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

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

Atorvastatin 10 mg(n = 20)

Atorvastatin 80 mg(n = 20)

•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

0.20 0.038

Un

its

0

0.3

0.5

0.4

Signal intensity at 12 weeks

(p < 0.0001)

Conclusions0.2

0.1

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)

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

Conclusions

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

(p = 0.47)

Abciximab(n = 401)

Placebo(n = 399)

Final infarct size

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

10

12

14

16

18

20

%

15.7 16.5

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

Conclusions

• 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

Presented by Dr. Shing-Chiu Wong at SCAI-ACC i2 Summit/ACC 2008

(p < 0.0001) (p = 0.67)

Time to hemostasis

Closure device

Manual pressure

Large (>6 cm) hematoma

min %

4.4 20.1 1.9 0.7

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)

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

Conclusions• 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

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

(p < 0.01)

Ezetimibe/ Simvastatin

(n = 357)

Simvastatin(n = 363)

(p = 0.20)

50

100

150

200

141

193

mg

/dl

0

LDL cholesterol New plaque formation

%

0

1

2

4

4.7

2.83

5

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

Conclusions

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

CORIO(n = 100)

SYMBIO(n = 101)

•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

39.8 20.4

%

0

40

10

In-stent restenosis

20

30

7.1

CoStar(n = 49)

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

Conclusions

• 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

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

(p = 0.77)

0

4

8

All-cause mortality

%

All-cause mortality

AED and CPR

CPR alone

6.4 6.5

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

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

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

(p = 0.04) (p = 0.02)

Cardiac index Left ventricular end-diastolic

volume

Istaroxime, 1.5 mcg/kg/min

Placebo

L/m

in/m

2

ml

-14.1 +3.9+0.3 -0.01

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

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

Conclusions

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

(p = 0.06)

Indapamide(n = 1,933)

Placebo(n = 1,912)

Strokes

•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

0

1

5

%

2.6 3.6 10.1 12.3

%

0

5

15

10

Mortality

(p = 0.02)

2

3

4

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%)

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

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

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

(p = 0.57)

Bivalirudin(n = 2,289)

UFH(n = 2,281)

(p = 0.008)

Composite endpoint Major bleeding

%

0

1

2

4

3.1 4.6

3

5

1

9

6

0

2345

78

10 8.3 8.7

%

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

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

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

(p = 0.03) (p = 0.44)

MC-1 Placebo

4-day mortality 30-day mortality

%

1 0.3

1.9 1.5

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

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

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

(p = 0.005) (p = 0.005)

Continuous aortic flow

augmentation

Medical management

Major bleeding Minor bleeding

%

16.5 5.1 26.6 8.5

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)

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

Conclusions

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

Telmisartan(n = 8,542)

Combination(n = 8,502)

•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

16.7 16.3

%

0

10

Primary endpoint

20

Ramipril(n = 8,576)

16.5

0

10

15

5

Mortality

11.6 12.5 11.8

%

(p < 0.004*) (p = ns)

* Telmisartan vs. ramipril for noninferiority

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

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

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

(p = 0.026) (p = 0.14)

Upstream tirofiban

Provisional tirofiban

>3 mm ST-elevation post-PCI

Mortality

%

36.6 44.3

2.8 4.0

1

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

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

Results

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

glimepiride(n = 273)

•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

0.73 -0.16

% c

han

ge

in a

ther

om

a v

olu

me

0

0.8

(p = 0.002)

Conclusions

Pioglitazone(n = 270)

0.2

0.4

0.6

-0.2

Primary endpoint CV mortality

%

0.4

0.8

1.2

0

(p = 0.37)

0.36 1.1

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

Conclusions

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

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

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

(p = ns)

%

19 33

Death or rehospitalization for heart failure

Rolofylline Placebo

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

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

(p = 0.1)

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

16 21%

Percentage worsened

CRT Medical therapy

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

Conclusions

• 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

p = ns p = ns

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

Autologous skeletal

myoblast cells

Medical therapy

Serious adverse events

Change in ejection fraction

%%

50 36 +0.3 -0.1

1

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)

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

XIENCE V(n = 223)

•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

0.33 0.34

mm

0

0.4

(p = 0.61)

Conclusions

TAXUS(n = 77)

0.1

0.2

0.3

In-stent late loss Stent thrombosis

%

0.4

0.8

1.2

0

(p = ns)

0.36 1.1

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

0.5

1.6

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

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

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

(p = 0.22) (p < 0.001)

0.25 0.51 43 28

Percent atheroma volume

Psychiatric symptoms

Rimonabant Placebo

% %

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)

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

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

Thrombus aspiration and PCI (n = 535)

PCI alone(n = 536)

%32

46

2.1 4

Good myocardial blush

Mortality

0

30

60

(p < 0.001) (p = 0.07)

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)

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

Conclusions

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

(p = 0.0013)

Pharmacoinvasive arm

(n = 522)

Standard therapy(n = 508)

Primary endpoint

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

•Optimal window: 6 hours

0

10

20

% 10.5

16.53.7 3.6

%

0

1

5

2

3

4

Mortality

(p = 0.94)

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

Conclusions

• 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

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

(p = 0.22)

Rosiglitazone Placebo

%

Change in saphenous vein graft plaque volume

0.9 2.8

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)

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

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

(p = 0.004)

Binodenoson(n = 402)

Adenosine(n = 404)

2nd or 3rd degree AV block

•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

0

1

%

0 3 30 50

%

0

30

50

40

Flushing

(p < 0.05)

2

3

Conclusions

20

10

ESC Congress 2008 ESC Congress 2008

Clinical Trial Summary SlidesClinical Trial Summary Slides

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

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

Presented by Dr. Marco Valgimigli at ESC 2008

(p = 0.009) (p = 0.006)

Tirofiban Placebo

Troponin I or T >3x ULN at 48 hours

MACE at 30 days

%21

37

20

35

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

Conclusions

• 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

Presented by Dr. John Alexander at ESC 2008

p = 0.005 for high-dose

vs. placebo

p = 0.09 for low-dose vs.

placebo

Apixaban

10 mg

Apixaban 5 mg

%

Placebo

7.9

5.7

3

ISTH major or clinically relevant nonmajor bleeding

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

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

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

Dronedarone(n = 2301)

Placebo(n = 2327)

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

•Head-to-head comparison with amiodarone awaited

6.0

0

5

10

Mortality

(p = 0.18)

Conclusions

%

10

%

5.05

0

1.21.8

(p = 0.027)

Stroke

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

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

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

(p = 0.94) (p = 0.55)

Ivabradine Placebo

CV death, MI, HF admission

All-cause mortality

% 10.4 10.1

15.4 15.3

%

0

5

15

2.0

9.9

20

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)

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

Conclusions

• 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

Presented by Dr. Akhil Kapur at ESC 2008

(p = 0.63)

CABG(n = 254)

PCI(n = 256)

(p = 0.001)

5

10

15

20

10.211.6%

0

Primary endpoint Repeat revascularization

10

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

Conclusions

• 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

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

(p = 0.005) (p = 0.47)

% 4.4

10.7

3.42.3

Transfer for PCI(n = 299)

Standard therapy (n = 301)

MACE Major bleeding

%

0

5

15

4.8

10.1

20

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

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

Conclusions

• 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

Presented by Dr. Don Poldermans at ESC 2008

(p = 0.016)

Fluvastatin XL(n = 250)

Placebo(n = 247)

(p = 0.039)

5

10

15

20

10.9

19.0

%

0

Myocardial ischemia CV death or MI

10

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

Conclusions

• 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

Presented by Dr. Dan Atar at ESC 2008

(p = 0.36)

FX04 Placebo

Total late enhancement zone at 4 months

(g) 15.4

19.3

%

0

5

15

3.0 4.0

20

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)

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

Conclusions

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

(p = 0.12)

n-3 PUFA(n = 3,494)

Placebo(n = 3,481)

(p = 0.013)

20

10

30 27.329.1

%

0

Mortality Arrhythmia related hospitalization

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

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

Conclusions

• 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

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

(p = 0.94) (p = 0.90)

Rosuvastati

nPlacebo

All-cause mortality

Death or hospital admission for CV

reasons

%

57 56

29 28

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

Conclusions

• 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

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

p = 0.009, change with

placebo

p = 0.71, change with darapladib

mm

3

Darapladib Placebo

Change in necrotic core volume at follow-up

-0.5

4.5

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

Conclusions

• 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

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

(p = 0.003 for non-inferiority) (p = 0.84)

Biolimus-eluting stent

Sirolimus-eluting stent

Death, MI, urgent revascularization

Stent thrombosis

%

1.9 2.0

9.210.5

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

Conclusions• 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

Presented by Dr. Dariusz Dudek at ESC 2008

(p = 0.28) (p = 0.74)

Aspiration thrombectomy

Primary PCI

ST-segment resolution at 60

minutes

6-month mortality

% 4.03.1

5041 %

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

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

Presented by Dr. Michal Tendera at ESC 2008

p = ns for stem cell LVEF change compared

with control

Selected

stem cells

Unselected stem cells

%

21 3720 35

Control

Change in LVEF at 6 months

3 3

0

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

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

(p = 0.1)

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

16 21%

Percentage worsened

CRT Medical therapy

%

0

1

2

44.1

2.53

5

SEAS

• 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

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

Conclusions

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

• Final full publication is awaited

Pedersen TR. Press release July 21, 2008

(p = NS)

Ezetimibe/ Simvastatin

(n = 943)

Placebo(n = 930)

(p = 0.05)

10

20

30

40 35.338.2

%

0

Composite endpoint Deaths from cancer

%

0

5

15

5.9

13.7

20

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)

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

Conclusions

• 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

Presented by Dr. Patrick Serruys at ESC 2008

(p = 0.0015)

CABG(n = 897)

DES-PCI(n = 903)

(p = 0.0001)

5

10

15

20

12.1

17.8

%

0

MACCE Repeat revascularization

10

%

0

5

15

8.8

3.0

20

SYNTAX Registry

• 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%)

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

Conclusions

• 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

Presented by Dr. Friedrich Mohr at ESC 2008

MACCE

Repeat revascularization

5

15

20

25

12.0

20.4

%

0DES-PCI (n = 198)

1010

20

25

10

CABG (n = 1,077)

%

0

5

15

6.0

2.0

20

TIME-CHF

• 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

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

Conclusions

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

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

Presented by Dr. H.P. Brunner-La Rocca at ESC 2008

Standard therapy(n = 248)

Intensified therapy(n = 251)

(p < 0.05)

Change in quality of life, Age ≥75 years

10

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

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

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

Presented by Dr. Andrea Frustaci at ESC 2008

(p < 0.05)

Immunosuppressive therapy(n = 43)

Placebo(n = 42)

-15

15

30 21.6

-8.1

% 0

Change in LVEF from baseline

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)

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

Conclusions

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

Telmisartan(n = 2,954)

Placebo(n = 2,972)

•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

15.7

%

0

10

Primary endpoint

2017.0

0

10

15

5

Mortality

12.3 11.7

%

(p = 0.22) (p = 0.49)

TCT 2008 TCT 2008

Clinical Trial Summary SlidesClinical Trial Summary Slides

%

0

5

15

2.00.4

20

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)

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

Conclusions

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

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

(p = 0.009)

Complex strategy(n = 250)

Simple strategy(n = 250)

(p > 0.05)

5

10

15

20

15.2

8.0

%

0

MACE Stent thrombosis

10

%

0

5

15

5.2

1.4

20

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)

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

Conclusions

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

Presented by Dr. Gregg Stone at TCT 2008

(p = 0.59)

Hypothermia(n = 63)

Routine management(n = 73)

(p = 0.22)

40

60

80

100

22.4

18.6

%

0

CIN Mortality

10

20

%

0

5

15

1.1 0.9

20

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)

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

Conclusions

• 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

Presented by Dr. Martin Leon at TCT 2008

(p = 0.93)

ZES(n = 773)

PES(n = 775)

(p = 1.0)

5

10

15

20

9.8 10.0%

0

MACE Stent thrombosis

10

%

0

5

15

1.83.0

20

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

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

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

Presented by Dr. Nico Pijls at TCT 2008

(p = 0.02)

FFR-guided PCI(n = 509)

Routine PCI(n = 496)

(p = 0.19)

5

10

15

20

13.2

18.4

%

0

MACE Death

10

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

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

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

(p = 0.005) (p < 0.001)

Bivalirudin alone

Heparin + GP IIb/IIIa inhibitor

Death, MI, TVR, stroke, or bleeding

Major bleeding

%

12.19.2

4.9 8.3

%

0

5

15

3.1 3.4

20

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)

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

Conclusions

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

• Mortality, stent thrombosis, MACE rates similar

Presented by Dr. Gregg Stone at TCT 2008

(p = 0.01)*

PES(n = 2,257)

SES(n = 749)

(p = 0.72)

5

10

15

20

8.1 8.0

%

0

MACE Stent thrombosis

10

* For non-inferiority

%

0

5

15

0.3 1.0

20

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

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

Conclusions

• 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

Presented by Dr. Julinda Mehili at TCT 2008

(p < 0.001)*

PES(n = 302)

SES(n = 305)

(p > 0.05)

5

10

15

20

13.615.8

%

0

MACE Stent thrombosis

10

* For non-inferiority

%

0

5

15

0.9 0.6

20

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

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

Conclusions

• 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

Presented by Dr. Robert Byrne at TCT 2008

(p = 0.003)

Dual-DES(n = 333)

SES(n = 335)

(p = 0.87)

5

10

15

20

12.011.0%

0

Angiographic restenosis Stent thrombosis

10

19.3

ZES(n = 339)

0.9

%

0

2019.3

31.5

100

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

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

Conclusions

(p < 0.05) (p < 0.05)

10

20

8.7 8.3%

0

Uncovered/malapposed struts (overlapping stents)

% intimal hyperplasia

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

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

Presented by Dr. Giulio Guagliumi at TCT 2008

0.051.8

SESn = 22

BMSn = 11

PESn = 22

ZESn = 22

80

60

4045.2

57.8

%

0

5

15

4.0

7.0

20

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

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

Conclusions

• 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

Presented by Dr. Karel Koch at TCT 2008

(p = 0.009)

Proxis + PCI(n = 141)

PCI alone(n = 143)

(p > 0.05)

66.0

50.0%

>70% STR post-PCI MACE

1040

60

80

100

0

20

%

0

5

15

1.2 0.2

20

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)

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

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

Presented by Dr. Jens Flensted Lassen at TCT 2008

ZES(n = 1,162)

SES(n = 1,171)

(p = 0.02)

Stent thrombosis

10

%

0

5

15

02.7

20

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)

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

Conclusions

• 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

Presented by Dr. Cheol-Hwan Lee at TCT 2008

(p = 0.83)

ZES(n = 108)

SES(n = 110)

(p = 0.17)

5

10

15

20

9.111.1%

0

MACE Stent thrombosis

109.1

PES(n = 110)

3.6

AHA 2008 AHA 2008

Clinical Trial Summary SlidesClinical Trial Summary Slides

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

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

Presented by Dr. Richard Nesto at AHA 2008

(p = 0.12)

Rosiglitazone Glipizide

Change in percent atheroma volume

%

-0.21

0.43

%

0

5

15

3.95.5

20

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)

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

Results

Conclusions • 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

Presented by Dr. C. Michael Gibson at AHA 2008

(p = 0.10)

Rivaroxaban(n = 1,166)

Placebo(n = 1,160)

(p = 0.028)

5

10

15

20

5.67.0

%

0

Primary outcome Death/MI/Stroke

10

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)

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

Conclusions• The diagnostic ability of MR-proADM for CHF

is unclear

• Clinical utility of these findings is limited

Presented by Dr. Stefan Anker at AHA 2008

(p < 0.001)

MR-proADM BNP

50

100

60.8

73.5

%

0

Prognostic accuracy in CHF patients

63.6

NT-proBNP

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)

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

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

Presented by Dr. Heinz Peter Schultheiss at AHA 2008

(p = 0.048)

IFNB-1b(n = 95)

Placebo(n = 48)

20

40

17

32

%

0

Viral load reduction or elimination

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

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

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

(p = NS)

Special intervention program

Control

Percent change in LDL cholesterol

%

-1.0

-2.0

ml/

min

/kg

0

0.7

0.1

1.0

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

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

Conclusions

• 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

Presented by Dr. David Whellan at AHA 2008

(p = 0.26)

Exercise training(n = 1,159)

Usual care(n = 1,172)

(p < 0.0001)

5

10

15

20

1213

m

0

Change in 6-minute walk distance

Change in Peak VO2

0.5

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

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

Presented by Dr. Kathryn Flynn at AHA 2008

(p = 0.001)

Exercise group Usual care

Change in Kansas City Cardiomyopathy Questionnaire at follow-up

Po

ints

5

2

%

0

5

15

10.7 10.7

20

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)

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

Conclusions

• 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

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

Presented by Dr. Peter Carson at AHA 2008

(p = 0.35)

Irbesartan(n = 2,067)

Placebo(n = 2,061)

(p = 0.98)

50

100

36.0 37.0

%

0

Primary outcome Mortality

10

%

0

5

15

2.7 3.0

20

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

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

Conclusions

• 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

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

Presented by Dr. Hisao Ogawa at AHA 2008

(p = 0.16)

Aspirin(n = 1,262)

No aspirin(n = 1,277)

(p = 0.67)

5

10

15

20

5.46.7

%

0

Atherosclerotic events Mortality

10

0

1.0

1.25

2

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)

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

Conclusions• 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

Presented by Dr. Paul Ridker at AHA 2008

(p < 0.00001)

Rosuvastatin(n = 8,901)

Placebo(n = 8,901)

(p = 0.02)

2

0.77

1.36

Eve

nts

/100

per

son

-yea

rs

0

Primary outcome All-cause mortality

1

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

1

Eve

nts

/100

per

son

-yea

rs

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)

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

Conclusions

• 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

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

Presented by Dr. J. Michael Gaziano at AHA 2008

Vit E n = 7,315

Placebon = 7,312

Placebon = 7,326

0

10

20

10

20

%

0

8.48.5 8.5 8.6%

Vit Cn = 7,329

Major cardiovascular events

(p = 0.86) (p = 0.91)

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)

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

Conclusions

(p > 0.05) (p > 0.05)

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

Presented by Dr. Rory Collins at AHA 2008

Simvastatin 80 mgn = 6,031

Placebon = 6,031

Simvastatin 20 mgn = 6,033

Folate/ Vit B12

n = 6,033

0

5050

%

0

25.524.5 25.724.8

%

%

0

5

15

4.96.0

20

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)

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

Conclusions

• 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

Presented by Dr. Shamir Mehta at AHA 2008

(p = 0.15)

Early invasive(n = 1,593)

Delayed invasive(n = 1,438)

(p = 0.81)

5

10

15

20

9.711.4%

0

Primary endpoint Mortality

10

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

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

Presented by Dr. Alan Jacobson at AHA 2008

(p = 0.1)

Patient self INR testing

Conventional INR testing

Death, stroke, or major bleeding

% p

er p

atie

nt-

year

7.9

8.9

%

0

5

15

01.8

20

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)

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

Conclusions • 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

Presented by Dr. Frank Paganelli at AHA 2008

(p = 0.03)

VASP-guided PCI(n = 214)

Routine PCI(n = 215)

(p = 0.06)

5

10

15

20

0.5

4.7

%

0

Stent thrombosis CV death

10