CVD and Diabetes Care:

The Alphabet Strategy  

Vinod PatelBSc (Hons) MD FRCP MRCGP DRCOG

Consultant Physician, Diabetes and Endocrinology Associate Professor in Clinical SkillsUniversity of Warwick Medical School

Leading causes of mortality

Adults, 2002

5823

4692

2399

1398

929

754

735

606

496

478

5823

4692

2399

1398

929

754

735

606

496

478

HIV/AIDS

Ischaemic heart disease

Tuberculosis

Road traffic accidents

Cerebrovascular disease

Self-inflicted injuries

Violence

Cirrhosis of the liver

Lower respiratory infections

Chronic obstruc. pulmonary disease

2279

1331

1037

811

783

672

475

382

352

343

2279

1331

1037

811

783

672

475

382

352

343

Ischaemic heart disease

Cerebrovascular disease

Chronic obstruc. pulmonary disease

Lower respiratory infections

Trachea, bronchus, lung cancers

Diabetes mellitus

Hypertensive heart disease

Stomach cancer

Tuberculosis

Colon and rectal cancers

15–59 60 and over

World Health Report 2003

(thousands)

Diabetes Care: The ComplicationsDiabetes Care: The Complications

RetinopathyRetinopathyMost common cause of Most common cause of

blindness in people of blindness in people of working ageworking age

NephropathyNephropathy16% of all new patients 16% of all new patients

needing renal replacement needing renal replacement therapytherapy

Erectile dysfunctionErectile dysfunctionMay affect up to 50% of May affect up to 50% of

men with long-men with long-standing diabetesstanding diabetes

Macrovascular disease Macrovascular disease 2–4 fold increased risk 2–4 fold increased risk of coronary heart disease of coronary heart disease

and stroke, 75% have and stroke, 75% have hypertensionhypertension

Foot problemsFoot problemsCommonest cause of non-Commonest cause of non-

traumatic amputationtraumatic amputation

The Audit Commission. Testing Times. A Review of Diabetes Services in England and Wales, 2000.

Public Health & Prevention

Primary

Experts

Secondary care

Tertiary

Secondary

Primary

Interface

………...Diagnosis……….General treatment……… Review

….… Screening…… Healthy eating…… Exercise……Weight care

Palliative …………………….…………………… Renal replacement ………………….. Amputation…………………. Rehabilitation………………… PCI / CABG……………….. Advanced eye surgery

……………… DKA…………….. Infections…………..... CVD…………... CVD Risk…………... Insulin start………….. Screening eyes………….Screening feet………….Screening renal…….…...Complex cases

Diabetes Chronic Disease Management

Single Team

A POETIC vision of HealthcareA POETIC vision of Healthcare

• P:P:– Patient-centred,Patient-centred, Patient Safe, Public Health-DrivenPatient Safe, Public Health-Driven

• O: O: – Objective-clear,Objective-clear, what is it that we desire to achieve and whywhat is it that we desire to achieve and why

• E:E:– Evidence-based,Evidence-based, audit-informed, research will be desirableaudit-informed, research will be desirable

• T:T: – Team orientated,Team orientated, multidisciplinary, well-trained, validatedmultidisciplinary, well-trained, validated

• I: I: – Integrated,Integrated, primary, secondary care, schools, community, councilsprimary, secondary care, schools, community, councils

• C:C: – Cost-effective,Cost-effective, cost efficient, but clinically governedcost efficient, but clinically governed

Need a Swiss Army Knife Approach!

Alphabet Strategy:Alphabet Strategy:QoF StandardsQoF Standards

• Advice: Advice: – exercise, diet, not smoking, exercise, diet, not smoking,

regular testing & clinicsregular testing & clinics

• Blood Pressure: Blood Pressure: – aim less than 140/80aim less than 140/80

• Cholesterol: Cholesterol: Creatinine CareCreatinine Care– less than 5less than 5

• Diabetes Control: Diabetes Control: – HbA1c% less than 7.5% HbA1c% less than 7.5%

• Eyes: Eyes: – check yearly at leastcheck yearly at least

• Feet: Feet: – check yearly at leastcheck yearly at least

• Guardian Drugs: Guardian Drugs: – Aspirin 75mgAspirin 75mg– ACE inhibitors, ARBsACE inhibitors, ARBs

Lifestyle changes reducing progression to DM

Diabetes Prevention Program Finnish Diabetes Prevention Study

7% weight loss in the obese > 5% weight loss

Avoid excess alcohol Fat intake < 30% of total calories

Diet advice Saturated fat < 10% of total calories

Smoking advice Fibre intake ≥ 15g per 1000 calories intake

150 mins of moderate exercise per week

Exercise > 4 hours per week

Other measures: increased veg/and fruits, less sugar/salt

Blood PressureUKPDS 38: 154/87 versus 144/82

UK Prospective Diabetes Study (UKPDS) Group (38). BMJ 1998;317:703–713

MI

Microvascular endpoint –34%

Heart failure –35%

Stroke –37%

All macrovascular endpoints –44%

Retinal photocoagulation –56%

Any diabetes-related endpoint –24%

0 -10 -20 -30 -40 -50

% Reduction in risk

-24 Significant

-34 Significant

-21 Non significant

-44 Significant

-56 Significant

-37 Significant

-35 Significant

Deaths reduced by 32%

• Primary Prevention Diabetes patients with one other risk factor (hypertension, smoker, micro-albuminuria, retinopathy)

Atorvastatin 10mg

Placebo

2838patients

Cholesterol CARDS Study

Placebo

CARDS Study: Treatment Effects

21 (1.5%)

24 (1.7%)

51 (3.6%)

83 (5.8%)

Atorva*

48% (11- 69)39 (2.8%)Stroke

31% (-16- 59)34 (2.4%)Coronary revascularisation

36% (9- 55)77 (5.5%)Acute coronary events

37% (17- 52)

p=0.001127 (9.0%)Primary endpoint**

Hazard Ratio Risk Reduction (CI)Placebo*Event

* N (% randomised)

.2 .4 .6 .8 1 1.2

Favours Atorvastatin Favours Placebo

**Fatal MI ,Other acute CHD death, non fatal MI, Unstable angina, CABG, Fatal stroke, non fatal stroke

Diabetes ControlUKPDS 33: HbA1c% 7.9% versus 7.0%

Intensively-treated patients: HbA1C = 7.0%

Conventionally-treated patients: HbA1C = 7.9%

This 0.9% decrease is associated with reduction in risk for:

MI: 16% p=0.052

Retinopathy: -21%

Cataract extraction: -24%

Microvascular endpoint: -25%

Albuminuria at 12 years: -34%

Any diabetes-related endpoint: -12%Significant

Significant

Borderline significance

Borderline significance

Significant

Significant

-12-12

-25-25

-16-16

-21-21

-34-34

-24-24

0 -10 -20 -30 -40 -50

% Reduction in risk

Risk of diabetes complications

The risk of diabetes complication based on the UKPDS Study. From Mogensten C-E . Diabetic nephropathy:evidence for renoprotection and practice. Heart 2000; 84(suppl): i26 -28 . Reproduced with permission from the BMJ Publishing Group.

E is for ....Eye screening

• Diabetic Maculopathy: Commonest cause of blindness in UK under 65

• Haemorrhages and/or hard exudates within one disc diameter of the macula, with or without visual loss

• Treatment: clinical risk factors (BP, Glycaemia, cholesterol) and focal laser photocoagulation

F is for ...F is for ...

FOOT SCREENINGFOOT SCREENING

Guardian Drugs

Aspirin 75mg od:

JBS 2 (2005) advocates considering aspirin 75mg od against CVD events in:

• Any established atherosclerotic disease

• ≥ 50 years, or those younger but have had diabetes for 10 years, or hypertenisve

• Retinopathy or nephropathy

• Once BP <150/90

• ACE-inhibitors and Angiotensin-II Receptor Antagonists have a special role in preventing diabetes complications (MICRO-HOPE, LIFE)

• ACE-inhibitors and Angiotensin-II Receptor Antagonists may have a special role in preventing diabetes

• Statins are guardian drugs

Guardian Drugs

RENAAL RENAAL Primary Primary ComponentsComponents

ESRDESRD

ESRD or DeathESRD or Death

Doubling of Serum CreatinineDoubling of Serum Creatinine

P (+ CT)L (+ CT)

Months

% w

ith

ev

ent

0 12 24 36 480

10

20

30

40

50

751 714 625 375 69762 715 610 347 42

Months

751 692 583 329 52762 689 554 295 36P (+ CT)

L (+ CT)

Months

% w

ith

ev

ent

0 12 24 36 480

10

20

30%

wit

h e

ven

t

p=0.006Risk Reduction: 25%

0 12 24 36 480

10

20

30

P

L

p=0.002Risk Reduction: 28%

P

L

P

L

p=0.010Risk Reduction: 20%

P (+ CT)L (+ CT) 751 714 625 375 69

762 715 610 347 42

•

B.Dahlof (Co-chair), P.Sever (Co-chair), N. Poulter (Secretary) H. Wedel (Statistician), G. Beevers, M. Caulfield, R. Collins

S. Kjeldsen, A. Kristinsson, J. Mehlsen, G. McInnes, M. Nieminen E. O’Brien, J. Östergren, on behalf of the ASCOT Investigators

A randomised controlled trial of the prevention of CHD and other vascular events by BP and

cholesterol lowering in a factorial study design

Study design

atenolol ± bendroflumethiazide

amlodipine ± perindopril

19,257 hypertensive

patients

PROBE design

ASCOT-BPLA

Investigator-led, multinational randomised controlled trial

placeboatorvastatin 10 mg Double-blind

ASCOT-LLA10,305 patients

TC ≤ 6.5 mmol/L (250 mg/dL)

Treatment algorithm to BP targets < 140/90 mm Hg or < 130/80 mm Hg in patients with diabetes

amlodipine 5-10 mg atenolol 50-100 mg

perindopril 4-8 mgbendroflumethiazide-K

1.25-2.5 mg

doxazosin GITS 4-8 mg

add

add add

additional drugs, eg, moxonidine/spironolactone

add

All patients in ASCOT have hypertension plus ≥ 3 risk factors for CHD

Patients with risk factor (%)

0 10 20 30 40 50 60 70 80 90 100

Hypertension

Age ≥ 55 years

Male

Microalbuminuria/proteinuria

Smoker

Family history of CHD

Plasma TC:HDL-C ≥ 6

Type 2 diabetes

Certain ECG abnormalities

LVH

Previous cerebrovascular events

Peripheral vascular disease

84

77

61

30

27

24

24

14

13

11

6

ASCOT patient populationrisk factor profile

100

Systolic and diastolic blood pressurem

m H

g

60

80

100

120

140

160

180

Time (years)

Baseline 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5

atenolol thiazide amlodipine perindopril

137.7

136.1

79.2

77.4

Mean difference 1.9

Last visit

Mean difference 2.7

SBP

DBP

163.9

164.1

94.8

94.5

Fatal and non-fatal stroke

Number at riskAmlodipine perindopril 9639 9483 9331 9156 8972 7863Atenolol thiazide 9618 9461 9274 9059 8843 7720

0.0 1.0 2.0 3.0 4.0 5.0 Years0.0

1.0

2.0

3.0

4.0

5.0

Amlodipine perindopril(No. of events 327)

Atenolol thiazide(No. of events 422)

HR = 0.77 (0.66 0.89)p = 0.0003

%

CV mortality

Number at riskAmlodipine perindopril 9639 9544 9441 9322 9167 8078Atenolol thiazide 9618 9532 9415 9261 9085 7975

0.0 1.0 2.0 3.0 4.0 5.0 Years0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

Amlodipine perindopril(No. of events 263)

Atenolol thiazide(No. of events 342)

HR = 0.76 (0.65 0.90)p = 0.0010

%

ASCOT: BPLA and LLA combined: Insight into optimal CV prevention

Endpoint

Amlodipine

perindopril + statin

Atenolol thiazide + placebo

Relative risk reduction

Fatal MI and non-fatal CHD

4.8 9.2 48%

Fatal and non-fatal stroke 4.6 8.2 44%

Rates / 1000 patient years

Doing all this Doing all this polypharmacypolypharmacy w will ill

poisonpoison our our patientspatients!!

Blood pressure, Cholesterol, Diabetes control, ACE-I, Aspirin!

The Steno-2 Study : The Steno-2 Study : AA Summary Summary

Steno Diabetes CentreSteno Diabetes Centre

Copenhagen, DenmarkCopenhagen, Denmark

• 160 with T2D and microalbuminuria160 with T2D and microalbuminuria

• 80 allocated to conventional treatment80 allocated to conventional treatment

• 80 allocated to intensive treatment80 allocated to intensive treatment

• Mean age 55.1 yearsMean age 55.1 years

• Mean follow-up 7.8 yearsMean follow-up 7.8 years

Steno-2 Steno-2 TTargetsargets

Steno-2 intensive Steno-2 intensive cohort %cohort %

JBS/AlphabetJBS/Alphabet

GuidelinesGuidelines

AAdvicedvice StandardStandard StandardStandard

BBlood Pressurelood Pressure 130 / 80 130 / 80

Earlier Earlier 140 / 85140 / 85

140 / 80140 / 80Optimal 130/80Optimal 130/80

GMS Audit 145/80GMS Audit 145/80

CCholesterolholesterol 4.54.5 4.04.0GMS Audit 5GMS Audit 5

DDiabetes Control : Hbiabetes Control : HbAA11cc%% 6.56.5%% 7.07.0%%GMS Audit 7.5%GMS Audit 7.5%

EEyesyes AnnuallyAnnually AnnuallyAnnually

FFeeteet AnnuallyAnnually AnnuallyAnnually

GGuardians : aspirinuardians : aspirin, , ACEI / ACEI / AIIAAIIA

AllAll MostMost

StatinsStatins mostmost AllAll

Steno 2: Event Reduction

53 %

61% 58%

67%

0

10

20

30

40

50

60

70

cardiovasculardisease

nephropathy retinopathy autonomicneuropathy

Nu m

b er

o f e

v en t

s

Steno-2 : CVD Event ReductionSteno-2 : CVD Event Reduction

EventEvent ConventionalConventional IntensiveIntensive

Cardiovascular DeathCardiovascular Death 77 …died earlier! …died earlier! 77

MI : non-fatalMI : non-fatal 1717 55

CABGCABG 1010 55

PCIPCI 55 00

Stroke : non-fatalStroke : non-fatal 2020 33

AmputationsAmputations 1414 77

Revascularisation for PVDRevascularisation for PVD 1212 66

P<0.002P<0.002

85 events in 35 85 events in 35 patientspatients

44% overall44% overall

33 events in 19 33 events in 19 patientspatients

24% overall24% overall

Steno-2 : CVD Deaths at 13 yearsSteno-2 : CVD Deaths at 13 years

EventEvent ConventionalConventional IntensiveIntensive

Cardiovascular DeathsCardiovascular Deaths

P<0.05P<0.05

Reduced by 57%!

Steno-2 : 13 years follow up dataSteno-2 : 13 years follow up data

EventEvent Reduction in Intensive GroupReduction in Intensive Group

All DeathsAll Deaths 46%46%

Cardiovascular DeathsCardiovascular Deaths 57%57%

Cardiovascular events Cardiovascular events 59%59%

End Stage Renal FailureEnd Stage Renal Failure 1 versus 6 patients1 versus 6 patients

Retinal Laser RxRetinal Laser Rx 55%55%

P<0.05P<0.05

Steno-2 : Conclusion

“ A target driven, long-term, intensified intervention aimed at multiple risk factors in patients with type 2 diabetes and microalbuminuria reduces the risk of cardiovascular and microvascular events by about 50%.”

Diabetes Passport

Diabetes Diabetes Polypill?Polypill?

X?Y?Z?A?B?

BMJ

Polypill Paper

SAMTA PillSAMTA Pill

StatinAspirinMetforminThiazideACE-I or ARB

Diabetes Polypill Approach?Diabetes Polypill Approach?

Indo-linguistically: “equality” ie in terms of reducing morbidity and mortality esp. CVD

Single approachDiabetes CHD Stroke Renal

A Advice Advice Advice Advice

B Blood Pressure Blood Pressure Blood Pressure Blood Pressure

CCholesterol

Creatinine

Cholesterol

Creatinine

Cholesterol

Creatinine

Cholesterol

Creatinine

D Diabetes control

Diabetes control Diabetes control Diabetes control

E EyesECG / ETT / Echocardiography

ECG and other Investigation

ESCRD Care

ECG, US, ?CT

F FeetFunctional status and follow up

Functional disability management

Functional management

G Guardian Drugs Guardian Drugs Guardian Drugs Guardian Drugs

Alphabet Strategy:Alphabet Strategy:QoF StandardsQoF Standards

• Advice: Advice: – exercise, diet, not smoking, exercise, diet, not smoking,

regular testing & clinicsregular testing & clinics

• Blood Pressure: Blood Pressure: – aim less than 140/80aim less than 140/80

• Cholesterol: Cholesterol: Creatinine CareCreatinine Care– less than 5less than 5

• Diabetes Control: Diabetes Control: – HbA1c% less than 7.5% HbA1c% less than 7.5%

• Eyes: Eyes: – check yearly at leastcheck yearly at least

• Feet: Feet: – check yearly at leastcheck yearly at least

• Guardian Drugs: Guardian Drugs: – Aspirin 75mgAspirin 75mg– ACE inhibitors, ARBsACE inhibitors, ARBs