DM and CVD Risk Prioritizing Elements of CVD Risk Management in Clinical Diabetes Practice - PowerPoint Presentation

Slide1

DM and CVD Risk Prioritizing Elements of CVD Risk Management in Clinical Diabetes Practice

Prof Kausik Ray,

BSc (

hons

),

MBChB

, MRCP, MD, MPhil (

Cantab

), FACC, FESC, FAHA

Professor of Cardiovascular Disease Prevention

St Georges University of London

Honorary Consultant Cardiologist St Georges Hospital

Slide2

IDF diabetes atlas, 4th edition, 2009

2010

2030

Total number of people with diabetes (age 20-79)

285 million438 millionPrevalence of diabetes (age 20-79)6.6 % 7.8 %

Prevalence of diabetes in 2030

Slide3

Coronary heart disease

Coronary death

Non-fatal myocardial infarction

Cerebrovascular disease

Ischaemic stroke

Haemorrhagic stroke

Unclassified stroke

Other vascular deaths

2.00 (1.83 - 2.19)

2.31 (2.05 - 2.60)

1.82 (1.64 - 2.03)

1.82 (1.65 - 2.01)

2.27 (1.95 - 2.65)

1.56 (1.19 - 2.05)

1.84 (1.59 - 2.13)

1.73 (1.51 - 1.98)

HR (95% CI)

26 505

11 556

14 741

11 176

3799

1183

4973

3826

Number

of cases

64 (54-71)

41 (24-54)

37 (19-51)

42 (25-55)

1 (0-20)

0 (0-26)

33 (12-48)

0 (0-26)

I

2

(95% CI)

1

1

2

4

Hazard ratio (diabetes vs. no diabetes)

Outcome

Lancet. 2010 Jun 26;375(9733):2215-22

Diabetes doubles the risk of vascular disease

Data from 528,877 participants (adjusted for age sex, cohort, SBP, smoking, BMI)

Slide4

Diabetes risk is not explained by conventional risk factors

Ischaemic stroke

Age and sex

Plus smoking status

Plus BMI

Plus SBP

Plus non-HDL-C

Plus HDL cholesterol

Plus log-triglycerides

2.06 (1.82-2.34)

2.10 (1.85-2.39)

2.00 (1.78-2.25)

1.91 (1.70-2.14)

1.93 (1.71-2.16)

1.87 (1.67-2.09)

1.87 (1.67-2.09)

HR (95% CI)

1

1

2

4

2.56 (2.15-3.05)

2.59 (2.16-3.09)

2.45 (2.08-2.88)

2.27 (1.94-2.65)

2.26 (1.94-2.64)

2.24 (1.94-2.60)

2.24 (1.94-2.59)

1

1

2

4

HR (95% CI)

Adjusted for

Coronary heart disease

1

1

2

4

1

1

2

4

Hazard ratio (diabetes vs. no diabetes)

Lancet. 2010 Jun 26;375(9733):2215-22

Slide5

DM duration matters to CVD

Men with

diabetes

without MI

Men with MINoneN=3197

Late onset

N=307

Mean duration

1.7 years

Early onset

N=107

Mean duration

16 years

Without diabetes

N=368

CVD events (n=534)

Age

1.00

1.59 (1.19,2.12)

2.61 (1.73,3.96)

2.35 (1.88,2.95)

Adj

1.00

1.53 (1.15,2.06)

2.52 (1.65,3.84)

2.23 (1.76,2.83)

Wannamethee

, Shaper,

Whincup

, Lennon,

Sattar

(Archives

Int

Med in press)

Slide6

Type 2 diabetes increases CHD/CVD risk over time

CVD/CHD risk at or prior to diagnosis is determined by conventional CHD risk factors

Hyperglycaemia in the diabetic range increases CHD risk over time

After a diabetes duration of >8 years CHD risk equivalence is reached

Sattar N. Diabetologia 2013;56:686-695.CHD riskAgeDiagnosis~8–10years’duration

CHD equivalence threshold

Slide7

Diabetes-related complications have declined substantially as preventive care has improved

A large burden of disease persists because of increased prevalence of diabetes

0.20

0.10

0.001086420

Rates of diabetes-related complications declined significantly between 1990 and 2010

Gregg EW et al. NEJM 2014;370:1514-1523

ESRD, end-stage renal disease

Events per 10,000 adult population

with diagnosed diabetes

150

125

100

755

50

25

4

2

0

Population with diabetes

Acute myocardial

infarction

Stroke

Amputation

ESRD

Death from hyperglycemic crisis

200520102000

19951990

Events per 10,000 overall adult population

Population with or without diabetes

Acute myocardial

infarction

Stroke

Amputation

ESRD

Death from hyperglycemic crisis

2005

2010

2000

1995

1990

Slide8

Prevention of Diabetes becomes increasingly essentialWhy ?

CV risk is incompletely explained by conventional risk factors

Prognosis is worse with duration

How ?Tackling Obesity/ sedentary lifestyle/ caloric intakeLegislation

Slide9

Question: 1 what modality best to lower CVD risk in DM ?

Question: 2 how intensive should therapy be?

BIGGEST BANK FOR YOUR BUCK?

Lipid-lowering?Blood pressure?Glucose-lowering? Aspirin? Lifestyle ?

Slide10

Statins- reduce CV events consistently(per 39mg/dl lower LDL-C)

CTT Lancet 2008 ,

371, 117-25

Slide11

Time to First Major Cardiovascular Event in Patients With Diabetes

*CHD death, nonfatal non

–

procedure-related MI, resuscitated cardiac arrest, fatal or nonfatal stroke

HR = 0.75 (95% CI 0.58, 0.97)

P

=0.026

Atorvastatin 10 mg

Atorvastatin 80

mg

0 1 2 3 4 5 6

Time (years)

0.20

0.10

0.15

0.05

0

Cumulative incidence of major cardiovascular events*

Relative risk reduction = 25%

Slide12

Fibrates ?

Slide13

Fibrates and CVD risk reduction among those with atherogenic

dyslipidemia

TG>200mg/dl and HDL <39mg/dl

Sacks et al NEJM 2010

Slide14

Summary on lipids in T2DM

Statin therapy remains the best lipid modifying agent

Lower cholesterol targets (intensive statins) based on absolute risk. 50% LDL-C reduction or LDL-C <70mg/dl or 30%/ 100mg/dl in lower risk

Fibrates, used as monotherapy or in combination therapy may have CVD benefit among those with atherogenic dyslipidemia and DM

Slide15

OutlineWhat is CVD risk in Diabetes?

Lipid-lowering?

Blood pressure?Glucose-lowering?

Aspirin?

Slide16

Diabetics derive similar proportional reductions in risk as non-diabetics with BP lowering

BP treatment

Trialists

. Archives 2005, 165, 1410-1419

Slide17

UKPDS lowering SBP reduces principally Strokes

BMJ 1998;317:703-713

Slide18

ACCORD

Average after 1

st

year: 133.5 Standard

119.3 Intensive, Delta = 14.2NEJM 2010, 362, 1575-1585

Slide19

Primary & Secondary Outcomes

Intensive

Events (%/yr)

StandardEvents (%/yr)HR (95% CI)P

Primary208 (1.87)237 (2.09)0.88 (0.73-1.06)0.20Total Mortality150 (1.28)144 (1.19)1.07 (0.85-1.35)0.55Cardiovascular Deaths60 (0.52)58 (0.49)1.06 (0.74-1.52)0.74Nonfatal

MI

126 (1.13)

146 (1.28)

0.87 (0.68-1.10)

0.25

Nonfatal

Stroke

34 (0.30)

55 (0.47)

0.63

(0.41-0.96)0.03

Total Stroke36 (0.32)62 (0.53)0.59 (0.39-0.89)

0.01

NEJM 2010, 362, 1575-1585

Slide20

BP summaryActual BP achieved critical rather than agent used

Meta-analysis

Target BP <140/90 SBP for all

More intensive target < 120 SBP results in stroke benefits

Slide21

OutlineWhat is CVD risk in Diabetes?

Lipid-lowering?

Blood pressure?Glucose-lowering?

Aspirin?

Slide22

Non-linear relationship between HbA1c and the risk of vascular complications and death: ADVANCE study

Zoungas

S. et al. Diabetologia 2012;55:636-643

Major

macrovascular

e

vents

Risk threshold:

HbA1c 7.0%

Major microvascular

e

vents

Risk threshold:

HbA1c 6.5%

All-cause death

Risk threshold:

HbA1c

7.0%

9.5

8.5

7.5

6.5

5.5

5

2

1

0.5

Mean HbA

1c duringfollow-up (%)67

89HR (95% CI)9.58.57.5

6.55.5

Mean HbA

1c

duringfollow-up (%)67

899.58.57.56.5

5.5

Mean HbA

1c

duringfollow-up (%)678

9

5

2

10.5HR (95% CI)

5

2

1

0.5

HR (95% CI)

Overall

Intensive group

Standard group

Slide23

Long-term beneficial effects on CVD risk following intensive treatment: DCCT/EDIC

0.12

0.10

0.08

0.060.040.020.00

Years since entry

Conventional therapy

Intensive therapy

1

2

3

4

5

6

7

8

910111221

0

Cumulative incidence of any predefined

cardiovascular outcome

705714

683688

629618

113

92

Intensive therapyConventional therapyNo. at risk*Nonfatal MI or stroke; CV death; subclinical MI; angina; or the need for revascularization with angioplasty or coronary-artery bypass

13

141516171819

2042% risk reductionP=0.02EDIC mean HbA1c over 11 years follow-up: 8.2%EDIC mean HbA1c over

11 years follow-up: 8.0%Nathan DM et al. N Engl J Med. 2005;353:2643-2653

Slide24

The vertical dashed line indicates the overall hazard ratio.

The

size of each square is proportional to the

number of patientsACCORD Study Group. N Engl J Med 2008;358:2545–2559

0.61.01.4p value

Favours intensive

Favours standard

0.04

0.03

Hazard ratio

(95% CI)

Primary outcome

Subgroup

Total

Previous CV event

No YesGlycated haemoglobin at baseline≤8.0%>8.0%

ACCORD: intensive glucose control beneficial in patients with no previous CVD or HbA1c <8%

Slide25

Endpoints

UKPDS

PROactive

ADVANCE

VADTACCORDOverallAv FU

10.1

2.9

5.0

5.6

3.5

4.95

Person years of FU

46 237

15 059

55 700

10 030

35 879

162 905

Difference

HbA1c

(%)

0.9

0.6

0.5

1.5

1.1

0.9

NF- MI

362

263

309

142

421

1495

CHD

685

366

647

167453

2318Strokes

238

193484

64148

1127Death from any cause

842363

1031197

460

2892

Ray KK, et al. Lancet. 2009;373:1765-1772

Slide26

Effects of more vs less intensive control of glucose on non-fatal MI, CHD, stroke and mortality

I

2

=0% (95% CI 0-69.3%), p=0.61

Overall

ADVANCE

ACCORD

PROactive

VADT

UKPDS

21.86

28.86

9.44

21.81

0.83

(0.75, 0.93)

0.98 (0.78, 1.23)

0.78 (0.64, 0.95)

0.83 (0.64, 1.06)

0.81 (0.58, 1.15)

0.78 (0.62, 0.98)

100.00

28.86

18.03

1

.4

.6

.8

1.2

1.4

1.6

1.8

2

Odds Ratio

Study

Intensive therapy better

Standard therapy better

Weight (%)

Odds Ratio

(95% CI)

Non-fatal MI

I

2=0% (95% CI 0-53%), p=0.78

Overall

UKPDS

PROactive*

Study

ACCORD

ADVANCE

VADT

0.85 (0.77, 0.93)

Odds Ratio

(95% CI)

100.00

20.22

25.68

36.48

9.03

0.75 (0.54, 1.04)

0.81 (0.65, 1.00)

0.82 (0.68, 0.99)

0.92 (0.78, 1.07)

0.85 (0.62, 1.17)

8.59

Weight (%)

1

.4

.6

.8

1.2

1.4

1.6

1.8

2

Odds Ratio

Intensive therapy better

Standard therapy better

CHD

I

2

=

0%

(95% CI

0-62%), p

= 0.70

Overall

ACCORD

ADVANCE

PROactive

†

UKPDS

VADT

†

0.93 (0.81, 1.06)

1.05 (0.76, 1.46)

0.91 (0.51, 1.61)

0.78 (0.47, 1.28)

16.21

5.18

0.97 (0.81, 1.16)

0.81 (0.60, 1.08)

100.00

51.38

20.47

6.76

1

.4

.6

.8

1.2

1.4

1.6

1.8

2

Odds Ratio

Intensive therapy better

Standard therapy better

Study

Odds Ratio

(95% CI)

Weight (%)

Stroke

Ray KK, et al.

Lancet.

2009; 373:1765–72

I

2

=58

% (95% CI

0-84

%),

p=0.049

Overall

ADVANCE

ACCORD

UKPDS

VADT

PROactive

1.02 (0.87, 1.19)

0.93 (0.82, 1.05)

1.28 (1.06, 1.54)

1.09 (0.81, 1.47)

0.96 (0.77, 1.19)

29.38

23.64

10.05

15.46

21.47

0.79 (0.53, 1.20)

100.00

1

.4

.6

.8

1.2

1.4

1.6

1.8

2

Odds Ratio

Intensive therapy better

Standard therapy better

Study

Odds Ratio

(95% CI)

Weight (%)

All-cause mortality

*Included

non-fatal myocardial infarction and death from all-cardiac mortality

.

†

Included

only non-fatal

strokes.

Slide27

CV risk reduction requires multiple interventions including

blood pressure and

lipid

managementPer 4mmHg lower SBPPer 1mmol/L lower LDL-C

Per 0.9% lower HbA1cBenefit of different interventions per 200 diabetic patients treated for 5 years*Comprised non-fatal myocardial infarction, coronary heart disease, stroke and all-cause mortalityRay KK, et al. Lancet. 2009;373:1765–72

Slide28

SummaryAn HbA1c of 6.6 vs 7.5 % over 5y results in

about a 15% lower risk of CHD

without an excess mortality risk

ButAbsolute benefit is modest

Slide29

OutlineWhat is CVD risk in Diabetes?

Lipid-lowering?

Blood pressure?Glucose-lowering?

Aspirin?

Slide30

 Effect of aspirin primary prevention of major CVD events in diabetes

De

Berardis

G et al. BMJ 2009;339:bmj.b4531

Slide31

Significant increase in risk of bleeding with aspirin

Slide32

Aspirin: summary for DM patientsMen- benefit on NFMI

Women none overall for any endpoint

Absolute benefits are modest and approximately equal to the risk of bleeding

For every 10, 000 people Tx in PP about 5 fewer NFMI, but 1 extra haemorrhagic stroke and 3 major bleeds

Slide33

Conclusions When you have it multimodality intervention to reduce macro-vascular and microvascular disease complications

Prevention is better than cure