l*esito dei diabetici dopo PCI è più spesso negativo

The bitter fate of acute coronary syndrome in
diabetics: diabetics have more adverse
outcomes after PCI
Sergio Berti
Fondazione CNR-Reg. Toscana G. Monasterio
Ospedale del Cuore, Massa
Prevalenza mondiale (%)
Diabetes in 2000 and forecast for 2030
5
4,4
500
4
366.000.000
400
3
2,8
171.000.000
forecast
300
2
200
1
100
0
0
2000
2030
Wild S et al. Diabetes Care 2004; 27: 1047-1053
Diabetes in 2000 and forecast for 2030
Hossain P et al. N Engl J Med 2007; 356: 213-215
Early mortality of diabetic and non-diabetic patients with
acute myocardial infarction: Historical perspective
Diabetes CVD(+)
Diabetes CVD(-)
No Diabetes CVD(+)
No Diabetes CVD(-)
UA/NSTEMI
69 Hosp. 8013 Pts
OASIS Registry
Malmberg K et al,
Circulation
2000;102:1014
Diabetes and Mortality Following Acute Coronary Syndromes
Sean M. Donahoe, MD at al. JAMA. 2007;298(7):765-775
Pooled TIMI Trials
Sean M. Donahoe, MD at al. JAMA. 2007;298(7):765-775
Cumulative Incidence of All-Cause Mortality Through 1
Year After ACS
Sean M. Donahoe, MD at al. JAMA. 2007;298(7):765-775
Cumulative Incidence of All-Cause Mortality Through 1
Year After ACS
30 days
8.5%
5.4%
2.1%
1.1%
Sean M. Donahoe, MD at al. JAMA. 2007;298(7):765-775
Cumulative Incidence of All-Cause Mortality Through 1
Year After ACS
1 year
13.2%
8.1%
7.2%
3.1%
Sean M. Donahoe, MD at al. JAMA. 2007;298(7):765-775
Spoke E
55 km
STEMI network
Massa-Carrara / Versilia
Zona Lunigiana
Matrix Network STEMI
1496 pts
Heart Hospital: STEMI network: Door to balloon
DtB (min)
200
180
160
140
120
107
103
111
100
102
98
95
2010
2011
88
80
60
40
20
0
2006
2007
2008
2009
2012
Heart Hospital: STEMI network: 1 year follow-up
mortality
14%
12%
10%
8%
6%
4%
2%
0%
2006
2009
2011
Patients presenting with STEMI
our experience (1496 pts)
8%
28%
with Diabetes
without Diabetes
Pre-Diabetes*
64%
*= HbA1c 6>x<6.49
Patients presenting with STEMI
our center experience
Overall Mortality
1
DM-
Survival, %
0.8
DM+
0.6
0.4
0.2
Log rank, p<0.001
0
400
800
1200
Follow-up, days
1600
Patients presenting with STEMI
our center experience
Overall Mortality
1
DMPre-diabetes *
Survival, %
0.8
DM+
0.6
0.4
0.2
Log rank, p<0.001 for both comparisons
0
400
800
1200
Follow-up, days
1600
*= HbA1c 6>x<6.49
…Worst outcome…
WHY ?
• Widespread and more aggressive atherosclerotic
disease in patients with Diabetes
• Lower response to the antiaggreganting agents
• Greater incidence of the “No reflow” phenomenon
• Comorbidities
• Less aggressive treatment strategies in diabetic
patients
Angiographic data in patients with and without Diabetes presenting
with ACS
All ACS
with Diabetes
5.50%
32.50%
Without Diabetes
7.90%
No obstructive
disease
Single-vessel
disease
62.00%
Multivessel disease
48,1%
44,0%
P value < 0.001
Sean M. Donahoe, MD at al. JAMA. 2007;298(7):765-775
Angiographic data in patients with and without Diabetes presenting
with ACS
UA/NSTEMI
with Diabetes
6.80%
27.20%
without Diabetes
10.70%
No obstructive
disease
Single-vessel
disease
65.90%
Multivessel
disease
50.80%
38.50%
P value < 0.001
Sean M. Donahoe, MD at al. JAMA. 2007;298(7):765-775
Angiographic data in patients with and without Diabetes presenting
with ACS
STEMI
without Diabetes
with Diabetes
3.70%
*
5.30%
*
No obstructive
disease
Single-vessel
disease
56.50%
39.80%
multivessel
disease
45.40%
49.40%
P value < 0.001
*P value 0.02
Sean M. Donahoe, MD at al. JAMA. 2007;298(7):765-775
Mechanisms contributing to platelet dysfunction
In patients with diabetes mellitus
HYPERGLYCAEMIA
Increased P-selectin
expression
ASSOCIATED
METABOLIC
CONDITIONS
DEFICIENT INSULIN
ACTION
Impaired response to
NO and PGI2
Osmotic effect
Decreased membrane
fluidity by glycation of
surface proteins
PLATELET
Obesity
IRS-dependent factors:
Increased intracellular
Ca++ degranulation
Activation of PKC
OTHER CELLULAR
ABNORMALITIES
ENDOTHELIAL
DYSFUNCTION
Dyslipidemia
Increased platelet turnover
Inflammation
Increased intracellular Ca++
Upregulation of P2Y12
signalling
Oxydative stress
H2O
PKC
IRS-1
Increased P-selectin and
GP expression
Ca++
ROS/NOS
Increased production of TF
Decreased NO and PGI2
production
TF
NO
PGI2
Endothelial cells
Ferreiro JL, Angiolllo DJ. Circulation 2011; 123: 798-813
Diabetes and Clopidogrel
Angiolillo DJ et al Diabetes 2005; 54:2430-5
Angiolillo DJ J Am Coll Cardiol 2006; 48:298-304
Diabetes and Prasugrel
TRITON TIMI 38
Wiviott SD Circulation 2008;118;1626-1636
PLATO diabetes:
All-cause mortality
10
8
All-cause mortality (%)
[James 2010:H,I]
Diabetes
Ticagrelor (n=2326)
Clopidogrel (n=2336)
HR (95% CI) = 0.82(0.66–1.01)
8.7%
7.0%
6
p for interaction = 0.66
5.0%
4
3.7%
No diabetes
Ticagrelor (n=6999)
Clopidogrel (n=6952)
HR (95% CI) = 0.77(0.65–0.91)
2
0
0
60
120
180
240
300
Days after randomisation
All-cause mortality benefit with ticagrelor was consistent with the
overall PLATO trial results[Wallentin 2009:J]
No interaction between diabetes status and treatment was observed (p=0.66)[James 2010:G,H]
CI, confidence interval; HR, hazard ratio.
James S, et al. Eur Heart J 2010;31:3006–3016.
360
The “no reflow” phenomenon
Multivariable Predictors of the No-Reflow Phenomenon
Iwakura et al. JACC Vol. 41, No. 1, 2003 January 1, 2003:1–7
The “no reflow” phenomenon
Myocardial Blush Grade
100.00%
Incidence %
80.00%
60.00%
No Diabetes
Diabetes
40.00%
20.00%
0.00%
0/1
2
3
Abhiram Prasad, MD at al. ACC Vol. 45, No. 4, 2005 February 15, 2005:508–14
Co-morbidities impact
60%
50%
40%
30%
20%
No diabetes
Diabetes
10%
0%
Solomon et al. Eur J Heart Fail 2010;12:1229-37
PVD, peripheral vessel disease;
CHF congestive heart failure
Under utilization of an early invasive treatment strategy in
diabetic patients with ACS
2005-2007
A nationwide study
N= 24952 pts.
What kind of stent?
DES
vs
BMS
DES vs BMS in diabetic patients
Restenosis
TLR
Patti G Am J Cardiol 2008;102:1328 –1334
DES vs BMS in diabetic patients
Death
Stent
Thrombosis
MI
Patti G Am J Cardiol 2008;102:1328 –1334
DES vs. BMS in Diabetic patients
William B. Hillegass, MD, at al. Journal of the American College of Cardiology Vol. 60, No. 22, 2012
How to prevent
cardiovascular events
in diabetic patients?
Better glycemic
control?
VADT
ACCORD
Sospeso per mortalità elevata
ADVANCE
UKPDS Trial
N Engl J Med 2008;359:1577-89.
Diabetes and ACS: “dangerous liasons”
• 65% of Diabetic Patients dies following cardiovascular events
• 37% of ACS Patients is diabetic
Diabetics with NSTEMI/UA, outcome is similar to non-diabetic
patients with STEMI
• Future risk cardiovascular events:
Diabetic Patients = non-diabetic patients with previous MI
Conclusions
Acute and
chronic tight
glycemic
control
Optimal
revascularization
strategy
Optimal
management of LV
dysfunction
Improve
antithrombotic
strategy
The bitter fate of acute coronary syndrome in
diabetics: diabetics have more adverse
outcomes after PCI
Sergio Berti
Fondazione CNR-Reg. Toscana G. Monasterio
Ospedale del Cuore, Massa