The bitter fate of acute coronary syndrome in

diabetics: diabetics have more adverse

outcomes after PCI

Sergio BertiFondazione CNR-Reg. Toscana G. Monasterio

Ospedale del Cuore, Massa

Diabetes in 2000 and forecast for 2030

4,4

2,8

012345

2000 2030

171.000.000

366.000.000

0

500

400

300

200

100

Prev

alen

za m

ondi

ale

(%)

Wild S et al. Diabetes Care 2004; 27: 1047-1053

forecast

Hossain P et al. N Engl J Med 2007; 356: 213-215

Diabetes in 2000 and forecast for 2030

Early mortality of diabetic and non-diabetic patients with acute myocardial infarction: Historical perspective

OASIS RegistryMalmberg K et al,Circulation 2000;102:1014

Diabetes CVD(+)

Diabetes CVD(-)

No Diabetes CVD(+)

No Diabetes CVD(-)

69 Hosp. 8013 Pts

UA/NSTEMI

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

Sean M. Donahoe, MD at al. JAMA. 2007;298(7):765-775

2.1%

8.5%

1.1%

5.4%

30 days

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

Sean M. Donahoe, MD at al. JAMA. 2007;298(7):765-775

7.2%

3.1%

13.2%

8.1%

1 year

STEMI network Massa-Carrara / Versilia

Spoke E 55 km

Zona Lunigiana

Matrix Network STEMI1496 pts

2006 2007 2008 2009 2010 2011 2012020406080100120140160180200

107 103 111102 98 95 88

DtB (min)

Heart Hospital: STEMI network: Door to balloon

Heart Hospital: STEMI network: 1 year follow-up mortality

2006 2009 20110%

2%

4%

6%

8%

10%

12%

14%

Patients presenting with STEMIour experience (1496 pts)

28%

64%

8%

with Diabeteswithout DiabetesPre-Diabetes*

*= HbA1c 6>x<6.49

Patients presenting with STEMIour center experience Overall Mortality

400

800

1200

1600

0

0.2

0.4

0.6

0.8

1

Follow-up, days

Sur

viva

l, %

DM-

DM+

Log rank, p<0.001

Patients presenting with STEMIour center experience Overall Mortality

400

800

1200

1600

0

0.2

0.4

0.6

0.8

1

Follow-up, days

Sur

viva

l, %

Log rank, p<0.001 for both comparisons

DM-

DM+

Pre-diabetes

*

*= HbA1c 6>x<6.49

• 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

…Worst outcome…WHY ?

Angiographic data in patients with and without Diabetes presenting with ACS

5.50%32.50%

62.00%

with Diabetes

No obstructive disease

Single-vessel disease

Multivessel disease

7.90%

44,0%

48,1%

Without Diabetes

All ACS

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

P value < 0.001

UA/NSTEMI

6.80% 27.20%

65.90%

with Diabetes

No obstructive disease

Single-vessel disease

Multivessel disease

10.70%

38.50%

50.80%

without Diabetes

Sean M. Donahoe, MD at al. JAMA. 2007;298(7):765-775

Angiographic data in patients with and without Diabetes presenting with ACS

P value < 0.001

STEMI

3.70%

39.80%56.50

%

with Diabetes

No obstructive diseaseSingle-vessel diseasemultivessel disease

5.30%

49.40%

45.40%

without Diabetes

*P value 0.02

* *

Sean M. Donahoe, MD at al. JAMA. 2007;298(7):765-775

Mechanisms contributing to platelet dysfunctionIn patients with diabetes mellitus

PKC

ROS/NOS

IRS-1 Ca++

TF

PGI2NO

Endothelial cells

H2OP2Y

12ADP

HYPERGLYCAEMIAIncreased P-selectin

expression

Osmotic effect

Activation of PKC

Decreased membrane fluidity by glycation of

surface proteins

DEFICIENT INSULINACTION

Impaired response toNO and PGI2

IRS-dependent factors:Increased intracellular

Ca++ degranulation

ASSOCIATED METABOLIC CONDITIONS

Obesity

Dyslipidemia

Inflammation

OTHER CELLULARABNORMALITIES

PLATELET ENDOTHELIALDYSFUNCTION

Increased platelet turnover

Upregulation of P2Y12 signalling

Increased intracellular Ca++

Oxydative stress

Increased P-selectin andGP expression

Increased production of TF

Decreased NO and PGI2 production

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 PrasugrelTRITON TIMI 38

Wiviott SD Circulation 2008;118;1626-1636

PLATO diabetes: All-cause mortality

CI, confidence interval; HR, hazard ratio.James S, et al. Eur Heart J 2010;31:3006–3016.

DiabetesTicagrelor (n=2326)Clopidogrel (n=2336)HR (95% CI) = 0.82(0.66–1.01)

No diabetesTicagrelor (n=6999)Clopidogrel (n=6952)HR (95% CI) = 0.77(0.65–0.91)

7.0%

8.7%

3.7%

5.0%

[James 2010:H,I]A

ll-ca

use

mor

talit

y (%

)

Days after randomisation

0 60 120 180 240 300 360

10

8

6

4

2

0

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]

p for interaction = 0.66

Multivariable Predictors of the No-Reflow Phenomenon

The “no reflow” phenomenon

Iwakura et al. JACC Vol. 41, No. 1, 2003 January 1, 2003:1–7

The “no reflow” phenomenon

0/1 2 30.00%

20.00%

40.00%

60.00%

80.00%

100.00%

No DiabetesDiabetes

Myocardial Blush GradeIn

cide

nce

%

Abhiram Prasad, MD at al. ACC Vol. 45, No. 4, 2005 February 15, 2005:508–14

Co-morbidities impact

Hypert

ensio

n

Renal

dysfuncti

on

Dialysi

sCHF

PVD

Previous S

troke

Chronic lung d

isease

0%

10%

20%

30%

40%

50%

60%

No diabetesDiabetes

PVD, peripheral vessel disease; CHF congestive heart failureSolomon et al. Eur J Heart Fail 2010;12:1229-37

Under utilization of an early invasive treatment strategy in diabetic patients with ACS

A nationwide study N= 24952 pts.2005-2007

What kind of stent?

DES

BMS

vs

DES vs BMS in diabetic patients

Patti G Am J Cardiol 2008;102:1328 –1334

Restenosis

TLR

Patti G Am J Cardiol 2008;102:1328 –1334

Death

StentThrombosis

MI

DES vs BMS in diabetic patients

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?

Sospeso per mortalità elevata

ACCORDVADT

ADVANCE

N Engl J Med 2008;359:1577-89.

UKPDS Trial

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

Improve antithrombotic

strategy

Acute and chronic tight

glycemic control

Optimal management of LV

dysfunction

Optimal revascularization

strategy

Conclusions

The bitter fate of acute coronary syndrome in

diabetics: diabetics have more adverse

outcomes after PCI

Sergio BertiFondazione CNR-Reg. Toscana G. Monasterio

Ospedale del Cuore, Massa