Difendiamo il cuore Tavola rotonda. Pistoia 16 febbraio 2008Dr Roberto Anichini Cardiovascular...

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Cardiovascular disease in diabetic patients: the facts

Cardiovascular disease accounts for 75% of death causes in Type 2 diabetic patients

Cardiovascular disease accounts for 75% of death causes in Type 2 diabetic patients

According to WHO the prevalence of CVD in diabetic patients ranges within 26 - 36%

The relative risk of CHD is 1.5-1.7 in male and 1.7-4.0 in female diabetic patients

In the diabetic patient life expectancy is 5 -10 years lower than in the non-diabetic general population

Decrease in CHD mortality rates between 1981 and

2000

Decrease in CHD mortality rates between 1981 and

2000

-70

-60

-50

-40

-30

-20

-10

0

Men WomenR

edu

ctio

n i

n C

HD

mo

rtal

ity

rate

s (%

)

– 62%

– 45%

Data from England and Wales between 1981 and 2000 in men and women aged 35–84 years. There were 68,230 fewer CHD deaths than expected from baseline mortality rates in 1981.

Unal B, et al. Circulation 2004; 109:1101–1107

Effect of risk factors/ treatments on CHD mortality

Effect of risk factors/ treatments on CHD mortality

2000

Dea

ths

prev

ente

d or

pos

tpon

ed in

200

0

• 68,230 fewer deaths in 2000Treatments 42%

Risk factors: better 71%

Risk factors: worse 13%

Year1981

10,000

0

–10,000

–20,000

–30,000

–40,000

–50,000

–60,000

–70,000

• e.g. diabetes, obesity

• e.g. smoking, cholesterol, BP

• e.g. secondary prevention, heart failure treatments

CHD deaths prevented or postponed by risk factor changes and treatments in England and Wales, 1981 to 2000

Unal B, et al. Circulation 2004; 109:1101–1107

• 2,888 more deaths due to diabetes• 2,662 more deaths due to physical inactivity• 2,097 more deaths due to obesity

12%

Stroke

Relative risk reductions for a 1% fall in HbA1c

P < 0.0001 for all reductions except stroke, P = 0.035

Diabetes-related death

14%

All-cause mortality

14%

Myocardial infarction

Microvascular disease

Stratton IM, et al. UKPDS 35. BMJ 2000; 321:405–412.

UKPDS: reducing blood glucose levels reduces the risk of complications

UKPDS: reducing blood glucose levels reduces the risk of complications

21%

37%

Over 10 years, each 1% reduction in HbA1c was associated with:

Any diabetes-related endpoint

21%

UKPDS: elevated blood glucose levels increase the risk of

diabetic complications

UKPDS: elevated blood glucose levels increase the risk of

diabetic complications

20

40

60

80

Incidence per1,000 patient-years

Study population: White, Asian Indian and Afro-Caribbean UKPDS patients (n = 4,585) Adjusted for age, sex and ethnic groupError bars = 95% CI

5 6 7 8 9 10 11

Myocardialinfarction

Microvasculardisease

Updated mean HbA1c (%)

00

Adapted from Stratton IM, et al. BMJ 2000; 321:405–412.

†Lower extremity amputation or fatal peripheral vascular disease*P = 0.035; **P < 0.0001 Adapted from Stratton IM, et al. UKPDS 35. BMJ 2000; 321:405–412.

UKPDS: increased risk of diabetes-related complications corresponding with a 1% increase

in HbA1c

UKPDS: increased risk of diabetes-related complications corresponding with a 1% increase

in HbA1c

Per

cen

tag

e in

crea

se i

n r

elat

ive

risk

co

rres

po

nd

ing

to

a 1

% r

ise

in H

bA

1c

0

5

10

15

20

25

30

35

40

45

50

**

Any diabetes-related endpoint

21%

**

Diabetes-related death

21% **

All cause

mortality

14%

*

Stroke

12%

**

Peripheral vascular disease†

43%

**

Myocardial infarction

14%

**

Micro-vascular disease

37%

**

Cataract extraction

19%

Observational analysis from UKPDS study data

1 Koro CE, et al. Diabetes Care 2004; 27:17–20. 2 Liebl A. Diabetologia 2002; 45:S23–S28.

La maggior parte dei pazienti diabetici di tipo 2 in USA e in Europa non è in

adeguato controllo glicemico

La maggior parte dei pazienti diabetici di tipo 2 in USA e in Europa non è in

adeguato controllo glicemico

Per

cen

tual

e d

i so

gg

etti

0

20

40

60

80

100

< 7% 7%

HbA1c (%)

US1

36%

64%

Per

cen

tual

e d

i so

gg

etti

0

20

40

60

80

100

6.5% > 6.5%

HbA1c (%)

EU2

31%

69%

Obiettivi glicemici definiti nel DMT2

1. American Diabetes Association. Diabetes Care 2004;27(suppl 1):S15―35.2. American Association of Clinical Endocrinologists. Endocr Pract 2002;8(suppl 1):43―84.3. Japan Diabetes Society. Available at: http://www.jds.or.jp.4. International Diabetes Federation. Diabet Med 1999;16:716―30.

*1―2 ore postprandiali; **2 ore postprandiali.

Controllo glicemico

Sani ADA1 AACE2 JDS3 IDF4

HbA1c (%) <6 <7 6.5 5.8―6.4 6.5

Glicemia a digiunommol/l (mg/dl)

<5.6 (<100)

5―7.2(90―13

0)

<6 (<110)

5.6―6.6 (100―11

9)

<6 (<110)

Glicemia postprandialemmol/l (mg/dl)

<7.8 (<140)

<10* (<180)

<7.8** (<140)

― <7.8** (<140)

Treat to target…….

Control blood glucose FPG <130 mg/dl

PPG <140 mg/dlHbA1c <6.5%

In quali pazienti?????

I livelli medi di HBA1c in Italia è di 8,6%......

Control blood glucose FPG <130 mg/dl

PPG <140 mg/dlHbA1c <6.5%

In quali pazienti?????

I livelli medi di HBA1c in Italia è di 8,6%......

0

10

20

30

40

50

60

70

80

Glycosylatedhemoglobin

<6.5%

Pat

ien

ts r

each

ing

inte

nsi

ve-t

reat

men

t g

oal

s at

mea

n 7

.8 y

(%

)

Intensive Therapyn = 67

Cholesterol<175 mg/dl

Triglycerides<150 mg/dl

Systolic BP<130 mm Hg

Diastolic BP<80 mm Hg

Conventional Therapyn = 63

P = 0.06

P < 0.001

P = 0.19

P = 0.001

P = 0.21

Adapted from Gaede P, et al. N Engl J Med 2003; 348:383–393.

Steno-2: effect of intensive vs conventional therapy on proportion of patients meeting goals

Steno-2: effect of intensive vs conventional therapy on proportion of patients meeting goals

Glycemic control and macrovascular diseaseMetaanalysis of RCT:s in type 1 & 2 diabetes

Incidence Rate Ratio

Incidence Rate Ratio (95% CI) % weight

Studies

Type 1 DM

(Stettler et al. Am Heart J 2006; 152:27-38)

Glycemic control and macrovascular diseaseMetaanalysis of RCT:s in type 1 & 2 diabetes

Incidence Rate Ratio (95% CI) % weight

Incidence Rate Ratio

Studies

Type 2 DM

(Stettler et al. Am Heart J 2006; 152:27-38)

Perché trattare precocemente e in maniera intensiva

Perché trattare precocemente e in maniera intensiva

Ka

pla

n-M

eie

r E

ve

nt

Ra

teTime to Death, MI or Stroke

Placebo

Pioglitazone

Placebo 358/ 2633 14.4%PIO 301 / 2605 12.3%

N events3-year estimate:

HR P value

PIO vs placebo

0.15

0.10

0.05

0

0 6 12 18 24 30 36TIME (months)

0.841 0.027

Ictus fatale e non fatale in pazienti con precedente ictus

Ictus fatale e non fatale in pazienti con precedente ictus

N a rischio:

Tempo dalla randomizzazione (mesi)

984 952 926 903 877 849 132

Kaplan-Meier % eventi

0.04

0.06

0.08

0.10

0.00

0.12

0 6 12 18 24 30 36

pioglitazone (27 / 486)

placebo (51 / 498)

0.02

0.0080.34, 0.850.53pioglitazone vs placebo

p value95% CIHR

- 47%

Studio AccordCirculation.National Heart lung and blood istitute 7.2.08

Studio AccordCirculation.National Heart lung and blood istitute 7.2.08

NHLBI ha deciso di stoppare il braccio dello studio della terapia intensiva diabetologica per eccesso di mortalità.

Nel gruppo di pazienti con obiettivo metabolico hba1c<6 si è avuto significativo incremento mortalità rispetto a Hba1c >7…. anche se minore

rispetto agli studi di controllo.

NHLBI ha deciso di stoppare il braccio dello studio della terapia intensiva diabetologica per eccesso di mortalità.

Nel gruppo di pazienti con obiettivo metabolico hba1c<6 si è avuto significativo incremento mortalità rispetto a Hba1c >7…. anche se minore

rispetto agli studi di controllo.

“The Metabolic Memory”Evidence for a long-term persistence of

hyperglycaemia-induced damage

N Engl J Med, 2005

DCC/EDIC Research Group

7

6

9

8

Hb

A1

c (%

)

10

OAD monotherapy

DietOAD

combinationOAD

+ basal insulin

Conservative management of glycemia:

traditional stepwise approach

OAD monotherapy

uptitration

Duration of diabetes

OAD + multiple dailyinsulin injections

OAD + basal insulin

OAD + multiple daily insulin injections

Diet

OAD monotherapy

OAD combinations

Proactive management of glycemia

OADs uptitration


7

6

9

8

Hb

A1

c (%

)

10

APRROCCIO PRECOCE EAGGRESSIVO

(insulin resistance and -cell dysfunction)

Campbell IW. Br J Cardiol 2000; 7:625–631.

Intervention!

Intervention!

Intervention!

Intervention!

Intervention!

Proactive management of glycemia

Intervention!


7

6

9

8

Hb

A1

c (%

)

10

Early aggressive approach in type 2 management. Intensive therapeutic strategy

Immediately upon diagnosis

Argomenti di discussione.Argomenti di discussione.

Quanto è importante il trattamento glicemico nella prevenzione secondaria delle pcv.??

A quali livelli glicemici??E’ impoetante la durata del diabete

nei target di trattamento??Trattamento precoce e aggressivo sia

nella prevenzione primaria e secondaria ?? (linee guida EASD-ADA)

Quanto è importante il trattamento glicemico nella prevenzione secondaria delle pcv.??

A quali livelli glicemici??E’ impoetante la durata del diabete

nei target di trattamento??Trattamento precoce e aggressivo sia

nella prevenzione primaria e secondaria ?? (linee guida EASD-ADA)

Intervallo di Tempo fino a: Decesso, IM (Silente Escluso) o Ictus

Intervallo di Tempo fino a: Decesso, IM (Silente Escluso) o Ictus

Tasso di eventi Kaplan-Meier

N at Risk:

5238 5102 4991 4877 4752 4651 786 (256)

Tempo dalla randomizzazione (mesi)0 6 12 18 24 30 36

0.0

0.05

0.10

0.15

pioglitazone

placebo

N eventi:

301 / 2605

358 / 2633

stima a 3 anni

12.3%

14.4%

HR 95% CI p value

pioglitazone vs placebo

0.841 0.722, 0.981 0.0273

-16%

IM fatale/non fatale (escluso IM silente)IM fatale/non fatale (escluso IM silente)

0.02

0.04

0.06

0.08

0.10

0 6 12 18 24 30 36

Kaplan-Meier event rate


N a Rischio: 2445 2387 2337 2293 2245 2199 399(139)


placebo (88 / 1215)

0.0

HR 95% CI p value


0.72 0.52, 0.99

0.045

-28%

Endpoint Cardiaco composto (Morte cardiaca, IM non fatale, Rivascolarizzazione coronarica o SCA)

Endpoint Cardiaco composto (Morte cardiaca, IM non fatale, Rivascolarizzazione coronarica o SCA)

N a Rischio:


HR 95% CI p value


0.81 0.66, 0.98

0.034

2445 2350 2260 2186 2116 2036 357(127)


0.05

0.10

0.15

0.20

0.0

0.25

0 6 12 18 24 30 36


placebo (217 / 1215)-19%

Sindrome Coronarica Acuta (SCA)

Sindrome Coronarica Acuta (SCA)


0.01

0.02

0.03

0.05

0.00

0.06

N a Rischio:

0 6 12 18 24 30 36



placebo (54 / 1215)

HR 95% CI p value


0.63 0.41, 0.97

0.035

0.04

2445 2397 2351 2308 2265 2222 406(139)

-37%

Difendiamo il cuore Tavola rotonda. Pistoia 16 febbraio 2008Dr Roberto Anichini Cardiovascular...

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Transcript of Difendiamo il cuore Tavola rotonda. Pistoia 16 febbraio 2008Dr Roberto Anichini Cardiovascular...