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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