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MH - D#1 - 10-ago-12 MH – D # 1 - 10-aug-12
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MH - D#2 - 10-ago-12 MH – D # 2 - 10-aug-12
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DISCLOSURE
I, Dr. Marcelo Halac, have the following potential conflicts of interest with this presentation to report:
Consulting
Grant Research
Employment in industry
Stockholder of a healthcare company
Owner of a healthcare company
Other(s)
I do not have any potential conflict of interest √
MH - D#3 - 10-ago-12 MH – D # 3 - 10-aug-12
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USA
2000: 15M
2025: 21.9M
JAPAN
2000: 6.9M
2025: 8.5M
EUROPE
2000: 30.8M
2025: 38.5M
AMERICAS (Exc-US)
2000: 20M
2025: 42M
AFRICA
2000: 9.2M
2025: 21.5M
ASIA
2000: 71.8M
2025: 165.7M
OCEANIA
2000: 0.8M
2025: 1.5M
Adapted from King H et al Diabetes Care 1998;21:1414-1431.
Diabetes Type II A prevalence around 300 millions is expected in 2025
MH - D#4 - 10-ago-12 MH – D # 4 - 10-aug-12
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USA
2000: 15M
2025: 21.9M
JAPAN
2000: 6.9M
2025: 8.5M
EUROPE
2000: 30.8M
2025: 38.5M
AMERICAS (Exc-US)
2000: 20M
2025: 42M
AFRICA
2000: 9.2M
2025: 21.5M
ASIA
2000: 71.8M
2025: 165.7M
OCEANIA
2000: 0.8M
2025: 1.5M
Adapted from King H et al Diabetes Care 1998;21:1414-1431.
• In 2K Diabetes was diagnosed in approximately 155 millions adults (83 millions male and 72 millions females.
• Between 1995 and 2025, prevalence of diabetes among adults will increase 35%.
Diabetes Type II A prevalence around 300 millions is expected in 2025
MH - D#5 - 10-ago-12 MH – D # 5 - 10-aug-12
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Death curves along time…
MH - D#6 - 10-ago-12 MH – D # 6 - 10-aug-12
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Nabel E and Braunwald E. N Engl J Med 2012; 366: 54-63
Historical overview of Cardiovascular Deaths
MH - D#7 - 10-ago-12 MH – D # 7 - 10-aug-12
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Nabel E and Braunwald E. N Engl J Med 2012; 366: 54-63
Historical overview of Cardiovascular Deaths
MH - D#8 - 10-ago-12 MH – D # 8 - 10-aug-12
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Nabel E and Braunwald E. N Engl J Med 2012; 366: 54-63
Historical overview of Cardiovascular Deaths
MH - D#9 - 10-ago-12 MH – D # 9 - 10-aug-12
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Nabel E and Braunwald E. N Engl J Med 2012; 366: 54-63
Historical overview of Cardiovascular Deaths
MH - D#10 - 10-ago-12 MH – D # 10 - 10-aug-12
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-50
-40
-30
-20
-10
0
10
20
30
40
50
80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98
Major CVD Mortality
% ∆
Mor
talit
y C
ambi
o (a
ge-a
djus
ted)
Centers por Disease Control and Prevention Mortality Database from Burgeoning Dilemmas in the Management of Diabetes and Cardiovascular Disease. BARI 2D Trial. Sobel BE et al. Circ 2003; 107: 636-42
Death curves along time…
MH - D#11 - 10-ago-12 MH – D # 11 - 10-aug-12
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-50
-40
-30
-20
-10
0
10
20
30
40
50
80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98
Cancer Mortality
Major CVD Mortality
% ∆
Mor
talit
y C
ambi
o (a
ge-a
djus
ted)
Centers por Disease Control and Prevention Mortality Database from Burgeoning Dilemmas in the Management of Diabetes and Cardiovascular Disease. BARI 2D Trial. Sobel BE et al. Circ 2003; 107: 636-42
Death curves along time…
MH - D#12 - 10-ago-12 MH – D # 12 - 10-aug-12
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-50
-40
-30
-20
-10
0
10
20
30
40
50
80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98
Diabetes Mortality
Cancer Mortality
Major CVD Mortality
% ∆
Mor
talit
y C
ambi
o (a
ge-a
djus
ted)
Centers por Disease Control and Prevention Mortality Database from Burgeoning Dilemmas in the Management of Diabetes and Cardiovascular Disease. BARI 2D Trial. Sobel BE et al. Circ 2003; 107: 636-42
Death curves along time…
MH - D#13 - 10-ago-12 MH – D # 13 - 10-aug-12
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Causes of death in diabetics
0
5
10
15
20
25
30
35
40
IHD OtherHeart D
DBT Ca Stroke Infection Other
Geiss LS et al. In: DBT in America. 2nd Edition 1995: 233-57
% d
eath
s
MH - D#14 - 10-ago-12 MH – D # 14 - 10-aug-12
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Causes of death in diabetics
0
5
10
15
20
25
30
35
40
IHD OtherHeart D
DBT Ca Stroke Infection Other
Geiss LS et al. In: DBT in America. 2nd Edition 1995: 233-57
% d
eath
s
IHD + Other Heart D + Stroke ≈ ⅔ deaths
MH - D#15 - 10-ago-12 MH – D # 15 - 10-aug-12
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140
120
100
80
60
40
20
0
Diabetics Non diabetics
CV
Dea
th R
ate
per 1
0000
pts
/yea
r (a
ge-a
djus
ted)
Adapted from Stamler J et al Diabetes Care 1993; 16: 434-444.
None One only Two only All three
Coronary Risk Factors
Cardiac Death risk: Diabetes vs All other Risk Factors (Total Serum Colesterol >200 mg/dl, Smoking, Sistolic Hypertension >120 mmHg)
MH - D#16 - 10-ago-12 MH – D # 16 - 10-aug-12
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140
120
100
80
60
40
20
0
Diabetics Non diabetics
CV
Dea
th R
ate
per 1
0000
pts
/yea
r (a
ge-a
djus
ted)
Adapted from Stamler J et al Diabetes Care 1993; 16: 434-444.
None One only Two only All three
Coronary Risk Factors
Cardiac Death risk: Diabetes vs All other Risk Factors (Total Serum Colesterol >200 mg/dl, Smoking, Sistolic Hypertension >120 mmHg)
MH - D#17 - 10-ago-12 MH – D # 17 - 10-aug-12
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140
120
100
80
60
40
20
0
Diabetics Non diabetics
CV
Dea
th R
ate
per 1
0000
pts
/yea
r (a
ge-a
djus
ted)
Adapted from Stamler J et al Diabetes Care 1993; 16: 434-444.
None One only Two only All three
Coronary Risk Factors
Cardiac Death risk: Diabetes vs All other Risk Factors (Total Serum Colesterol >200 mg/dl, Smoking, Sistolic Hypertension >120 mmHg)
MH - D#18 - 10-ago-12 MH – D # 18 - 10-aug-12
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Burke AP et al. Morphologic findings of coronary atherosclerotic plaques in diabetics: a postmortem study. Arterioscler Thromb Vasc Biol. 2004 Jul;24(7):1266-71. Epub 2004 May 13
Diabetic Coronary Arteries
Type II-DM
Type I-DM
Non DM
MH - D#19 - 10-ago-12 MH – D # 19 - 10-aug-12
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Atherectomy material = 47 pts
22
12
62
40
0
20
40
60
80
Macrophages Thrombosis
Diabetics Non Diabetics
p=0.03
p=0.04
Plaque burden in Diabetics
Coronary composition and macrophage infiltration in atherectomy specimens from patients with diabetes mellitus. Moreno PR et al. Circ 2000; 102: 2180-4
MH - D#20 - 10-ago-12 MH – D # 20 - 10-aug-12
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Atheroesclerotic Plaque composition in Diabetics
A. Diabetics B. Non Diabetics
Coronary composition and macrophage infiltration in atherectomy specimens from patients with diabetes mellitus. Moreno PR et al. Circ 2000; 102: 2180-4
Endartherectomy rescued material = 47 pts.
Macrophages and
Thrombosis
MH - D#23 - 10-ago-12 MH – D # 23 - 10-aug-12
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DBT leads to a Prothrombotic State
Endotelial Dysfunction 1
Platelet Dysfunction 2
Smooth Muscle Proliferation 3
Higher
Restenosis 4
1 De Vriese AS et al. Br J pharmacol 2000; 130; 963-74 2 Angiolillo D et al. Diabetes 2005; 54: 2430-5 3 Suzuki LA et al. Diabetes 2001; 50: 851-60 4 Elezi S et al. J Am Coll Cardiol 1998; 32: 1866-73
MH - D#24 - 10-ago-12 MH – D # 24 - 10-aug-12
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Diabetics are pts with a more complex disease
Smaller vessels More MVD Higher rate of calcified lesions Higher incidence of Type C
lesions In-stent restenosis increased More comorbidities
(Hypertension, Hyperlipidemias, CKD)
MH - D#25 - 10-ago-12 MH – D # 25 - 10-aug-12
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What we know about Diabetes…
• DBT ≡ CAD (CAD = ⅔ of DBT Deaths)
• Almost ⅛ of adult pop has DBT or Impared
Fasting Glucose (≈ ⅓ >60yrs)
• CAD in DBT is more severe and diffuse than in
non-DBT
• 49% of DBT has CAD in autopsy
• Case Fatality Rate higher in DBT
Kirtane A @ TCT 2011
MH - D#26 - 10-ago-12 MH – D # 26 - 10-aug-12
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But a vast majority of this patients are asymptomatic.
MH - D#27 - 10-ago-12 MH – D # 27 - 10-aug-12
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Asymptomatic Pts: Mayo Observational Studies SPECT Scanning
• 58% of the pts had an abnormal SPECT scan (826 of 1427) • 18% High Risk Scan (those with angiography 61% high risk CAD)
Rajagopalan N et al. Identifying high-risk asymptomatic diabetic patients who are candidates for screening stress single-photon emission computed tomography imaging. J Am Coll Cardiol 2005 Jan 4; 45(1): 43-9.
MH - D#29 - 10-ago-12 MH – D # 29 - 10-aug-12
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Asymptomatic Diabetic Pts: Routine Screening should be a “must”?
Young et al. JAMA 2009; 301: 1547-55
DIAD Study (1123 pts, 4.8 yrs Follow Up)
MH - D#31 - 10-ago-12 MH – D # 31 - 10-aug-12
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CV Risks in Symptomatic vs Asymptomatic diabetic pts
MACE and Cardiac Risks in Symp vs Asymp patients 300 pts undergoing angiography; symptoms assessed at Cath Lab
Choi et al. Diabetic Medicine 2007; 24: 1003-11
3-fold higher rate of revascularization among symptomatic pts
MH - D#34 - 10-ago-12 MH – D # 34 - 10-aug-12
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Our first approach was shakespearean: to revascularize or
not to revascularize
MH - D#35 - 10-ago-12 MH – D # 35 - 10-aug-12
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0
0,2
0,4
0,6
0,8
1
1 2 3 4 5 6 7 8 9 10
Surv
ival
(%)
Years
CABG Non Diab 78.2% 734 p
PCI Non Diab 76.8% 742 p
BARI Diabetics vs Non-Diabetics: 10-yrs Survival
Gersh BJ – TCT 2002
CABG vs PCI in Non Diabetics p=0.50
MH - D#36 - 10-ago-12 MH – D # 36 - 10-aug-12
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0
0,2
0,4
0,6
0,8
1
1 2 3 4 5 6 7 8 9 10
Surv
ival
(%)
Years
CABG Non Diab 78.2% 734 p
PCI Non Diab 76.8% 742 p
CABG Diab 57.1% 180 p
PCI Diab 44.1% 173 p
BARI Diabetics vs Non-Diabetics: 10-yrs Survival
Gersh BJ – TCT 2002
CABG vs PCI in Non Diabetics p=0.50 CABG vs PCI in Diabetics p=0.012
MH - D#37 - 10-ago-12 MH – D # 37 - 10-aug-12
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BARI Registry Diabetics vs Non-Diabetics: 5-yrs Survival
Detre et al. Circulation 1999
PCI Registry n=182
CABG Registry n=117
1
0.5
0 1 2 3 4 5 F/Up (years)
Surv
ival
5-yrs Mortality PCI Registry vs CABG Registry
14.4% vs 14.9%
MH - D#38 - 10-ago-12 MH – D # 38 - 10-aug-12
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BARI II 2D
Early Coronary Revasularization Hypothesis Glicemia Control Hypothesis
Medical Treatment + Effective Revascularization
(CABG+pci) OMT Insulin Drugs to diminish
insulin-resistance
Composite Endopoint = 5-yrs Mortality
Burgeoning Dilemmas in the Management of Diabetes and Cardiovascular Disease. BARI 2D Trial. Sobel BE et al. Circ 2003; 107: 636-42
BARI 2D
2800 pts
Stable CAD candidates for revasc + Type II DBT
MH - D#39 - 10-ago-12 MH – D # 39 - 10-aug-12
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13,2% 13,5%
0%
5%
10%
15%
20%
Revasc. OMT
• The 5-year death rate for the group receiving revascularization plus optimal medical therapy was 13.2% vs. 13.5% in the group receiving optimal medical therapy alone.
• The difference between the two treatment groups did not reach statistical significance.
Dea
th (
%)
BARI 2D Trial: Primary Endpoint
n =155 n =161
p = 0.97
BARI 2D Study Group, NEJM 2009
MH - D#40 - 10-ago-12 MH – D # 40 - 10-aug-12
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Then we tried to answer whether DES were more convenient than BMS for
this patients subgroup.
MH - D#41 - 10-ago-12 MH – D # 41 - 10-aug-12
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Patti G et al. Meta-Analysis Comparison (Nine Trials) of Outcomes With Drug-Eluting Stents Versus Bare Metal Stents in Patients With Diabetes Mellitus. Am J Cardiol 2008;102:1328 –1334
Meta-analysis BMS vs 1st Generation DES in Diabetics
MH - D#42 - 10-ago-12 MH – D # 42 - 10-aug-12
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But… all the DES can reach the same goals?
MH - D#43 - 10-ago-12 MH – D # 43 - 10-aug-12
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Diabetics have a higher global risk SIRTAX LATE: MACE at 5 yrs
PCI w/DES: 201 pts w/DBT and 811 without DBT
Raber L et al. EuroPCR 2011
MH - D#45 - 10-ago-12 MH – D # 45 - 10-aug-12
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TAXUS Trials- Restenosis in NIDDM
32,9
4,4
37,5
6,6
0
10
20
30
40
In Stent In Segment
Control
TAXUS
p<0.0001
p<0.0001
↓ 87% ↓ 82% B
inay
Res
teno
sis
MH - D#46 - 10-ago-12 MH – D # 46 - 10-aug-12
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TLR Reduction across TAXUS Trials
TAXUS TAXUS TAXUS TAXUS II IV VI II IV VI IV VI IV VI
↓71% ↓70%
↓51%
↓85%
↓64%
↓80%
↓63%
↓85%
↓65% ↓68%
Non Diabetics All Diabetics Diabetics on Oral agents
Diabetics on Insulin
MH - D#47 - 10-ago-12 MH – D # 47 - 10-aug-12
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Reality Trial Clinical events at 8 mo
MH - D#48 - 10-ago-12 MH – D # 48 - 10-aug-12
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Reality Trial: Diabetics Subgroup Clinical events at 8 mo
Maurice MC et al. JAMA 2006; 295: 895-904
MH - D#49 - 10-ago-12 MH – D # 49 - 10-aug-12
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ISAR-DIABETES: Randomized Comparison of CYPHER vs TAXUS in Diabetics
Dibra A et al. NEJM 2005; 27: 260-6
MH - D#50 - 10-ago-12 MH – D # 50 - 10-aug-12
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Nowadays we need to answer if , regarding diabetics, second or new-
generation DES are an advance over first-generation stents
MH - D#51 - 10-ago-12 MH – D # 51 - 10-aug-12
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EES vs PES in Diabetics
Stone G et al. Differential Clinical Responses to Everolimus-Eluting and Paclitaxel-Eluting Coronary Stents in Patients With and Without Diabetes Mellitus. Circulation. 2011; 124: 893-900
Prospective, Randomized Clinical Evaluation of the Xience V Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions (SPIRIT) Trial and a Trial of Everolimus-Eluting Stents and Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice (COMPARE)
MH - D#52 - 10-ago-12 MH – D # 52 - 10-aug-12
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Stone G et al. Differential Clinical Responses to Everolimus-Eluting and Paclitaxel-Eluting Coronary Stents in Patients With and Without Diabetes Mellitus. Circulation. 2011; 124: 893-900
Time-to-event curves for major adverse cardiac events (cardiac death, myocardial infarction or ischemia-driven target lesion revascularization)
MH - D#53 - 10-ago-12 MH – D # 53 - 10-aug-12
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Cardiac Death ►
◄ Myocardial Infarction
TLR ►
Stone G et al. Circulation. 2011; 124: 893-900
MH - D#54 - 10-ago-12 MH – D # 54 - 10-aug-12
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Stent Thrombosis according to the Academic Research Consortium definition of definite or probable
Stone G et al. Differential Clinical Responses to Everolimus-Eluting and Paclitaxel-Eluting Coronary Stents in Patients With and Without Diabetes Mellitus. Circulation. 2011; 124: 893-900
MH - D#55 - 10-ago-12 MH – D # 55 - 10-aug-12
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EES vs SES in Diabetics
Junker A et al. TCT 2011
SORT OUT IV: Diabetes Subgroup Analysis Randomized trial of DES in all-comer PCI pts
Cypher Select® vs Xience V®
MH - D#57 - 10-ago-12 MH – D # 57 - 10-aug-12
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a Serryus P et al. Comparison of zotarolimus-eluting and everolimus-eluting coronary stents. N Engl J Med 2010 Jul 8;363(2):136-46. Epub 2010 Jun 16. b Silber S. Unrestricted randomised use of two new generation drug-eluting coronary stents: 2-year patient-related versus stent-related outcomes from the RESOLUTE All Comers trial. Lancet 2011 Apr 9;377(9773):1241-7. Epub 2011 Apr 1.
EES vs ZES in Diabetics RESOLUTE All Comers Trial TLR in Xience V vs Resolute
MH - D#58 - 10-ago-12 MH – D # 58 - 10-aug-12
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P=NS
EES vs ZES in Diabetics Pooled Resolute Trials:
TLR @1 year
Silber S et al. TCT 2011. Abstract 181
P=NS
MH - D#59 - 10-ago-12 MH – D # 59 - 10-aug-12
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EES vs ZES in Diabetics Pooled Resolute Trials:
Definite/Probable Stent Thrombosis @1 year
Silber S et al. TCT 2011. Abstract 181
MH - D#60 - 10-ago-12 MH – D # 60 - 10-aug-12
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TUXEDO-India
MH - D#61 - 10-ago-12 MH – D # 61 - 10-aug-12
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MH - D#62 - 10-ago-12 MH – D # 62 - 10-aug-12
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MH - D#63 - 10-ago-12 MH – D # 63 - 10-aug-12
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MH - D#65 - 10-ago-12 MH – D # 65 - 10-aug-12
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Conclusions
Diabetics are a higher-risk group of patients for adverse outcomes after our stent procedures.
MH - D#66 - 10-ago-12 MH – D # 66 - 10-aug-12
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Conclusions
Diabetics are a higher-risk group of patients for adverse outcomes after our stent procedures.
We definitely have good evidence that DES are a better option than BMS for diabetics.
MH - D#67 - 10-ago-12 MH – D # 67 - 10-aug-12
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Conclusions
Diabetics are a higher-risk group of patients for adverse outcomes after our stent procedures.
We definitely have good evidence that DES are a better option than BMS for diabetics.
Among the current new-generation DES and acording to actual EBM, stents are probably as good as each other in treating this patient subset.
MH - D#68 - 10-ago-12 MH – D # 68 - 10-aug-12
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Thanks for your attention! www.solaci.org
