Prof. Stefano Carugo › diapositive › guest › 2017 - Carugo Stefano - Trattamento...

Trattamento della cardiopatia ischemica del paziente diabetico

Milano 7 Luglio 2017

Prof. Stefano CarugoDiapositiva preparata da Stefano Carugo e ceduta alla Società Italiana di Diabetologia.

Per ricevere la versione originale si prega di scrivere a [email protected]

Haffner SM et al - N Engl J Med 1998

Diabetes increases coronary mortality with and without a prior MI

Diapositiva preparata da Stefano Carugo e ceduta alla Società Italiana di Diabetologia.


Modeling of Years of Life Lost by Disease Status of Participants atBaseline Compared With Those Free of Diabetes, Stroke, and

Myocardial Infarction (MI)

The emerging risk factors collaboration, JAMA 2015



Glycaemic continuum and cardiovascular disease



Carte del rischio cardiovascolare Uomini diabetici



Carte del rischio cardiovascolareDonne diabetiche



Macrophages infiltration(From coronary atherectomy)

Moreno PR et al. Circulation 2000

Diabetes mellitus Non Diabetes mellitusDiapositiva preparata da Stefano Carugo e ceduta alla Società Italiana di Diabetologia.


Inflammation in coronary arteries in diabetic and non-diabetic patients

Burke PA et al. Arterioscler Thromb Vasc Biol 2004



Macrophages infiltrates and necrotic core size

Burke PA et al. Arterioscler Thromb Vasc Biol 2004



IVUS-VH in diabetic and non diabetic patients

Diabetic Non-diabetic



La soglia di percezione del dolore anginoso risulta più alta

a causa della neuropatia autonomica che coinvolge l’innervazione sensitiva del cuore



Ruolo della resistenza all’insulina nel determinare incremento pressorio

Reddy KJ et al. J Cardiovasc Med. 2010



CARDIOLOGI CLINICI:

CARDIOLOGI INTERVENTISTI:

DIABETOLOGI:

dr. Luigi Oltrona Visconti, Pavia dr.ssa Roberta Rossini, Bergamodr. Niccolò Grieco, Milano dr. Antonio Mafrici, Milano

dr. Giuseppe Musumeci, Bergamodr. Corrado Lettieri, Mantovadr. Stefano De Servi, Legnanodr. Carlo Sponzilli, Milano

dr. Roberto Trevisan, Bergamodr. Emanuele Perseghin, Monzadr. Antonio Cimino, Brescia

Documento di posizione“SCA-Diabete”

Aumentare il grado di appropriatezza secondo uno

standard di qualità

GISE Lombardia, ANMCO Lombardia, LombardIMA, SID Lombardia, AMD Lombardia



ACP=adenosine disphosphate; GP=glycoprotein; IRS-1=insulin receptor substrate-1; NO=nitric oxide; PGI2=prostacyclin; PKC= protein kinase C; TF=tissue factor.Reprinted with permission from Ferreiro JL, Angiolillo DJ. Circulation 2011 123:798-813.

Mechanisms Involved in Platelet Dysfunction in Diabetes Mellitus

Endothelial Cells

Hyperglycemia Deficient InsulinAction

AssociatedMetabolicConditions

Other CellularAbnormalities

Increased P-selectinexpression

Osmotic effect

Activation of PKCDecreased membranefluidity by glycationof surface proteins

Impaired response toNO and PGI2

IRS-dependent factors:Increased intracellular Ca++

Degranulation

Obesity

Dyslipidemia

Inflammation

Platelet EndothelialDysfunction

Increased platelet turnover

Increased intracellular Ca++

Upregulation of P2Y12signaling

Oxidative stress

Increased P-selectin andGP expression

Increased production of TF

Decreased NO andPGI2 production

H2O



0

10

20

30

40

50

60

70

80

% P

late

leta

ggre

gatio

n(L

TA)

ADP 6µM

p<0.0001

ADP 20µM

p<0.0001

NDM NIDDM IDDM NDM NIDDM IDDM

Platelet Function According to Hypoglycemic Treatment

Angiolillo DJ et al. J Am Coll Cardiol 2006; 48: 298-304



No. at RiskSTEMIDiabetes 7156 6508 2947 2653 2118 1610No diabetes 39421 37136 16685 15274 12276 9351

UA/NSTEMIDiabetes 3457 3313 2923 2339 1317 924No diabetes 12002 11658 10505 8191 5141 4008

Donahoe SM et al. JAMA. 2007;298:765-75.

Cumulative Incidence of All-Cause Mortality Through 1 Year After ACS

Diabetes Subgroup Analysis 11 TIMI Trials, >62,000 pts10,613 diabetics (17.1%)

P<0.0001 STEMI

P<0.0001 UA/NSTEMI

P<0.0001

P<0.0001

0 30 90 180 270 360Days after ACS

Mor

talit

y, %

STEMI

Diabetes

UA/NSTEMI

No DiabetesDiabetesNo Diabetes

14

12

10

8

6

4

2

0



Diabetes as Predictor of Stent Thrombosis at 1 Year in the Era of DES

0

1

2

3

4

5 OR=2.0(0.8-4.9)

OR=2.8(1.7-4.3)

HR=3.7(1.7-7.9)

HR=2.03(1.07-3.83)

IDDM IDDM Diabetes Diabetes

Kuchulakanti et al.Circulation 2006

Urban et al.Circulation 2006

Iakovou et al.JAMA 2005

Daemen et al.Lancet 2007

Odd

s/ha

zard

ratio



78%

14%

8%P=0.04

Influence of Diabetes Mellitus on Clopidogrel-induced Antiplatelet Effects

Angiolillo DJ et al. Diabetes. 2005;54:2430-5.

Responders(Platelet inhibition >30%)

Low responders(Platelet inhibition 10-29%)

Non-responders(Platelet inhibition <10%)

56%6%

38%

DM No-DM

Acute Phase of Treatment Long-term Phase of Treatment

24 hrs post 300 mg LD

Angiolillo DJ et al. J Am Coll Cardiol. 2006;48:298-304.

0

20

40

60

80

Plat

elet

agg

rega

tion

(%)

P=0.002P<0.0001

ADP 20µM ADP 6µM

DM No DM DM No DMDiapositiva preparata da Stefano Carugo e ceduta alla Società Italiana di Diabetologia.


CURRENT-OASIS= Clopidogrel Optimal Loading Dose Usage to Reduce Recurrent Events Optimal Antiplatelet Strategy for Interventions; PCI=percutaneous intervention; PLATO= A Study of Platelet Inhibition and Patient Outcomes; TRITON-TIMI= Trial To Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel Thrombolysis in Myocardial Infarction.Reprinted with permission from Ferreiro JL, Angiolillo DJ. Circulation 2011. 123:798-813.

Efficacy of New Drugs/Approaches in Reducing Adverse Outcomes in Diabetes Mellitus From Large-Scale Clinical Trials

TRITON-TIMI 38 17.0 12.2 0.70 (0.58 – 0.85)

PLATO 16.2 14.1 0.88 (0.76 – 1.03)

CURRENT OASIS 7 5.6 4.9 0.87 (0.66 – 1.15)(PCI Cohort)

Study % of Events Hazard Ratio (95% confidence interval)Standard New Drug/Approach

New Drug/ApproachBetter

Standard ClopidogrelBetter

0 0.5 1 1.5



Recommendations for antiplatelet therapy in patients with diabetes



Algoritmo della SCA



LG ESC 2016 NSTEMI Nei Pazienti diabetici



Total and Cardiovascular Death

Hakeem A, et al. J Am Heart Assoc. 2013

RR = 1.51

- SYNTAX- FREEDOM- VA CARDS- CARDIA

TOTALRR = 1.57

CABG vs PCI in diabetics with MVD: Comprehensive SystematicReview and Meta-analysis of Randomized Clinical Data (3052 pts)



1. Il paziente diabetico richiede l’impiego di una terapia antiaggregante ad hoc

2- Considerare una strategia early invasive

3- Scelta individualizzata della strategia di rivascolarizzazione (chirurgica vs percutanea)

4- Trattamento aggressivo delle dislipidemie

SCA e Diabete :i 4 “must”!



Conclusions

• Platelets from patients with diabetes mellitus are dysfunctional:increased platelet reactivityreduced responsiveness to antiplatelet agents

• Increased platelet reactivity and reduced responsiveness to standard dual antiplatelet treatment regimens (aspirin plus clopidogrel) are associated with atherothrombotic risk.

• Potent antithrombotic strategy

• Potent antidyslipidemia treatment

• Best revascularization option should be decided on a patient basis

• Early invasive approach is recommended



Grazie per l’attenzione



Prof. Stefano Carugo › diapositive › guest › 2017 - Carugo Stefano - Trattamento...

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