canadian diabetes association clinical practice guidelines vascular protection in people with...

Canadian Diabetes Association Clinical Practice Guidelines

Vascular Protection in People with Diabetes Chapter 22

James A. Stone, David Fitchett, Steven Grover, Richard Lewanczuk, Peter Lin

guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association

Vascular Protection Checklist 2013

A • A1C – optimal glycemic control (usually ≤7%)

B • BP – optimal blood pressure control (<130/80)

C • Cholesterol – LDL ≤2.0 mmol/L if decided to treat

D • Drugs to protect the heart (regardless of baseline BP or LDL)

A – ACEi or ARB │ S – Statin │ A – ASA if indicated

E • Exercise / Eating healthily – regular physical

activity, achieve and maintain healthy body weight

S • Smoking cessation


20-30 31-40 41-45 46-50 51-55 56-60 61-65 66-70 71-75 76-80 81-85

Absolute Risk of MI is Higher in Patients with DM

Age group

0.5

1.0

1.5

2.0

2.5

3.0

0No

. ev

ents

per

100

per

so

n-

year

s

Booth GL, et al. Lancet 2006;368:29-36.

All lines fitted according to a polynomial equation; R2= 0.99–1.00 for each

MI = myocardial infarction

Diabetes n = 379,003 No Diabetes n = 9,018,082 Database 1994-2000

No diabetesMen

Women

DiabetesMen

Women


MRFIT: Impact of Diabetes on Cardiovascular Mortality

Mor

talit

y pe

r 10

,000

140

120

100

80

60

40

20

0None

6

One only Two only All three

Number of risk factors*

1222

47

31

59

91

125Nondiabetes (n = 342,815)

Diabetes (n = 5,163)

*Risk factors analyzed: smoking, hypercholesterolemia and hypertension.

Stamler J, et al. Diabetes Care 1993; 16(2):434-44


T2DM for > 15 Years Duration Confers a Similar Risk of Fatal CHD as Prior CHD and No Diabetes

20 year follow-up of 121,046 women aged

30 to 55 years in Nurses’

Health Study

Hu F, et al. Arch Intern Med. 2001;161:1717-1723.


Multifaceted Management is Essential for T2DM

• Intensive multifaceted management in patients

with Type 2 diabetes lowers overall mortality

• Multifaceted treatment strategy includes:– Glucose, lipid, BP control

– Health behavior optimization

– Use of vascular protective medications


STENO-2


Multifaceted Approach for CVD Prevention Among Patients with T2DM

Type 2 Diabetes +

Microalbuminuria

n = 160

Conventional ArmMD follows clinical practice guidelines

8-year follow-up composite outcome:CV death, MI, CABG, PCI, Stroke, Amputation, or PVD surgery

Gaede et al. NEJM. 2003: 348;383-393

Intensive ArmTherapies to achieve targets in glycemia, lipids, BP and microalbuminuria

Multidisciplinary care q3mo

ASA and ACE inhibitors

(independent of BP)


Gaede et al. NEJM. 2003: 348;383-393

STENO-2: Intensive Group Achieved Targets


Intensive Group had Improved CV Outcomes

12 24 36 48 60 72 84 960

10

20

30

40

50

60P = 0.007

Conventional therapy

Intensive therapy

Months of Follow-upRRR= relative risk reduction

53 % RRRAny CV event

NNT = 5

Gaede et al. NEJM. 2003: 348;383-393


Gaede et al. NEJM. 2003: 348;383-393

STENO 2 – Microvascular Disease


Use a Multifaceted Vascular Protection Strategy

BP <130/80

A1C ≤7%

Rx:StatinsACEi/ARB

Healthy Lifestyle/weight Smoking Cessation

PhysicalActivity

Vascular protective medications

• Statins

• ACE-inhibitors or Angiotensin receptor

blockers (ARB)

• ASA selective use


HPS: Statin Therapy Beneficial Among Patients with Diabetes

(10269) (10267)SIMVASTATIN PLACEBO Rate ratio & 95% CI

STATIN better PLACEBO better

999 1250(23.5%) (29.4%)Previous MI

460 591(18.9%) (24.2%)Other CHD (not MI)

No prior CHD

172 212(18.7%) (23.6%)CVD

327 420(24.7%) (30.5%)PVD

276 367(13.8%) (18.6%)Diabetes

24%reduction(P<0.00001)

2033 2585(19.8%) (25.2%)ALL PATIENTS

0.4 0.6 0.8 1.0 1.2 1.4

HPS Lancet 2002;360:7-22

HPS: Heart protection study


CARDS: Effect of Statin for PRIMARY Prevention in DM

• n = 2838• Age 40-75, no history of CVD• T2DM plus one or more:

– Retinopathy– Albuminuria– Hypertension– Smoking

• Intervention: Atorvastatin 10 mg vs. Placebo• Outcome: ACS, revascularization, stroke

Colhoun HM, et al. Lancet 2004;364:685.


CARDS: Statins Reduced CVD in Patients with DM

Colhoun HM, et al. Lancet 2004;364:685.


• ≥40 yrs old or • Macrovascular disease or• Microvascular disease or• DM >15 yrs duration and age >30 years or• Warrants therapy based on the 2012 Canadian

Cardiovascular Society lipid guidelines

Among women with childbearing potential, statins should only be used in the presence of proper preconception counseling &

reliable contraception. Stop statins prior to conception.

2013Who Should Receive Statins? (regardless of baseline LDL-C)


What if baseline LDL-C ≤2.0 mmol/L?

• Within CARDS and HPS, the subgroups that started

with lower baseline LDL-C still benefited to the same

degree as the whole population

• If the patient qualifies for statin therapy based on the

algorithm, use the statin regardless of the baseline

LDL-C and then target an LDL reduction of ≥50%

HPS Lancet 2002;360:7-22 Colhoun HM, et al. Lancet 2004;364:685.



• Statins


blockers (ARB)



Association of SBP and CV Mortality in Men With T2DM

250

200

150

100

50

0<120 120-139 140-159 160-179 180-199

SBP (mmHg)

CV

mor

talit

y ra

teP

er 1

0,00

0 pe

rson

-yea

rs

No diabetesDiabetes

≥200

Stamler J, et al. Diabetes Care. 1993;16:434-444.


UKPDS Study Group. BMJ 1998; 317:703-13.

50

40

30

20

10

0

Years from randomization

Pat

ient

s w

ith e

vent

s (%

)

0 1 2 3 4 5 6 7 8 9

Less tight control (mean BP 154/87 mmHg)

Tight control (mean BP 144/82 mmHg)

Tight BP control:24% reduction of events(95% CI 8-38)

Tight BP control:24% reduction of events(95% CI 8-38)

Hypertension in Diabetes UKPDS


P<0.005

MI,

str

oke,

CV

m

orta

lity/

1000

pt-

yDiabetes Subgroup

90 mm Hg (n=501) 85 mm Hg (n=501) 80 mm Hg (n=499)

Goal of therapy: target diastolic BP

24.4

18.8

11.9

30

25

20

15

10

5

0Hansson et al. Lancet. 1998;351:1755.

HOT: BP Control Reduces CV Events


Micro-HOPE (ACEi): CV Benefits

RR = 0.67 (0.5-0.9) p = 0.0074

RR = 0.78 (0.64-0.94) p = 0.01

RR = 0.63 (0.49-0.79) p = 0.001

Stroke(NNT 53)

CV Death(NNT 29)

MI(NNT 37)

0 400 800 12001600

0

0.1

0.2Placebo

Ramipril 10 mg

Primary Outcome (NNT 22)

0 400 800 1200 16000

0.08

0.16 All Mortality(NNT 31)

RR = 0.76 (0.63-0.92) p = 0.004

0 1000 2000

0

0.06

0.12

0 1000 2000

0

0.04

0.08

0 1000 20000

0.08

0.16

Duration of follow-up (days)

Kap

lan

-Mei

er r

ates RR = 0.75 (0.64-0.88)

p = 0.0004

HOPE study investigators. Lancet. 2000;355:253-59.


ONTARGET: ARB Therapy is as Effective as ACEi for CVD Prevention

ONTARGET study investigators. NEJM. 2008:358:1547-59.


Who Should Receive ACEi or ARB Therapy?(regardless of baseline blood pressure)

• ≥55 years of age or • Macrovascular disease or • Microvascular disease

At doses that have shown vascular protection [perindopril 8 mg daily (EUROPA), ramipril 10 mg daily

(HOPE), telmisartan 80 mg daily (ONTARGET)]

Among women with childbearing potential, ACEi or ARB should only be used in the presence of proper preconception

counseling & reliable contraception. Stop ACEi or ARB either prior to conception or immediately upon detection of pregnancy

2013

EUROPA Investigators, Lancet 2003;362(9386):782-788.HOPE study investigators. Lancet. 2000;355:253-59.

ONTARGET study investigators. NEJM. 2008:358:1547-59


• Statins


blockers (ARB)



What About ASA for 1 Prevention of CVD? ⁰

Included: Six studies, n = 10,117 participants

De Berardis G et al. BMJ 2009;339:b4531


JPAD = Japanese Primary Prevention of Atherosclerosis with Aspirin for DiabetesPOPADAD = Prevention of Progression of Arterial Disease and DiabetesPPP = Primary Prevention ProjectETDRS = Early Treatment Diabetic Retinopathy StudyPHS = Physicians’ Health StudyWHS = Women’s Health Study

De Beradis G, et al. BMJ 2009; 339:b4531.

ASA for 1⁰Prevention in DiabetesMeta analysis of 6 studies(n = 10,117)

No overall benefit for: • Major CV events • MI• Stroke• CV mortality• All-cause mortality

0.03 0.125 0.5 12

8Favors ASA Favors control/placebo

JPADPOPADADWHSPPPETDRSTotal

68/1262105/63858/51420/519

350/1856601/4789

86/1277108/63862/51322/512

379/1855657/4795

0.80 (0.59-1.09)0.97 (0.76-1.24)0.90 (0.63-1.29)0.90 (0.50-1.62)0.90 (0.78-1.04)0.90 (0.81-1.00)

Major CV events

No. of events/No. in group

ASA Control/placebo RR (95% CI) RR (95% CI)

JPADPOPADADWHSPPPETDRSPHSTotal

28/126290/63836/5145/519

241/185611/275

395/5064

14/127782/63824/51310/512

283/185526/258

439/5053

0.87 (0.40-1.87)1.10 (0.83-1.45)1.48 (0.88-2.49)0.49 (0.17-1.43)0.82 (0.69-0.98)0.40 (0.20-0.79)0.86 (0.61-1.21)

Myocardial infarction

JPADPOPADADWHSPPPETDRSTotal

12/126237/63815/5149/519

92/1856181/4789

32/127750/63831/51310/51278/1855

201/4795

0.89 (0.54-1.46)0.74 (0.49-1.12)0.46 (0.25-0.85)0.89 (0.36-2.17)1.17 (0.87-1.58)0.83 (0.60-1.14)

Stroke

JPADPOPADADPPPETDRSTotal

1/126243/63810/519

244/1856298/4275

10/127735/6388/512

275/1855328/4282

0.10 (0.01-0.79)1.23 (0.80-1.89)1.23 (0.49-3.10)0.87 (0.73-1.04)0.94 (0.72-1.23)

Death from CV causes

JPADPOPADADPPPETDRSTotal

34/126294/63825/519

340/1856493/4275

38/1277101/63820/512

366/1855525/4282

0.90 (0.57-1.14)0.93 (0.72-1.21)1.23 (0.69-2.19)0.91 (0.78-1.06)0.93 (0.82-1.05)

All-cause mortality


Insufficient evidence to support use of ASA for primary prevention

Risk of bleeding CVD protection

2013

ASA Not Routinely Recommended for 1 ⁰Prevention for CVD Among Patients with DM


• Do your part

• Protect their heart

Multifaceted approach + Individualize therapy

Don`t Forget To…………..


Vascular Protection Checklist 2013

A • A1C – optimal glycemic control (usually ≤7%)

B • BP – optimal blood pressure control (<130/80)

C • Cholesterol – LDL ≤2.0 mmol/L if decided to treat

D • Drugs to protect the heart (regardless of baseline BP or LDL)

A – ACEi or ARB │ S – Statin │ A – ASA if indicated

E • Exercise / Eating healthily – regular physical

activity, achieve and maintain healthy body weight

S • Smoking cessation

guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca


1. All individuals with diabetes (type 1 or type 2) should follow a comprehensive, multifaceted approach to reduce cardiovascular risk including:– Achievement and maintenance of healthy body weight– Healthy diet– Regular physical activity– Smoking cessation– Optimal glycemic control (usually A1C <7%)– Optimal blood pressure control (<130/80 mmHg)– Additional vascular protective medications in the majority

of adult patients

[Grade D, consensus for T1DM, children/adolescents; Grade A, Level 1 for T2DM]

Recommendation 1


Recommendation 2

2. Statin therapy should be used to reduce CV risk in

adults with type 1 or type 2 diabetes with any of the

following features:– Clinical macrovascular disease [Grade A, Level 1]

– Age ≥40 years [Grade A, Level 1 T2DM; Grade D Consensus T1DM]

– Age <40 and one of the following:

• Diabetes duration > 15 years and age >30 yrs

• Microvascular complication

• Warrants therapy for other reasons based on the 2012

CCS guidelines for the management of dyslipidemia [Grade D, consensus]

2013


Recommendation 3

3. ACE inhibitor or ARB, at doses that have

demonstrated vascular protection, should be used

to reduce CV risk in adults with type 1 or type 2

diabetes with any of the following: – Clinical macrovascular disease [Grade A, Level 1]

– Age ≥55 years [Grade A, Level 1 for those with an additional risk factor

or end organ damage; Grade D, consensus for all others]

– Age <55 years and microvascular complications [Grade

D, consensus]

2013


Among women with childbearing

potential, ACE inhibitor, ARB, or statin

should only be used if there is reliable

contraception.


Recommendation 4

4. ASA should not be routinely used for the primary

prevention of cardiovascular disease in people with

diabetes [Grade B, Level 2]

ASA may be used in the presence of additional cardiovascular risk factors [Grade D, Consensus]

2013


Recommendation 5 and 6

5. Low-dose ASA therapy (81–325 mg) may be used

for secondary prevention in people with

established cardiovascular disease [Grade D, Consensus]

6. Clopidogrel (75 mg) may be used in people unable

to tolerate ASA [Grade D, Consensus]


CDA Clinical Practice Guidelines

www.guidelines.diabetes.ca – for professionals

1-800-BANTING (226-8464)

www.diabetes.ca – for patients

http://guidelines.diabetes.ca/

http://diabetes.ca/

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