GUIDELINESWHATS NEW AND WHATS NOT

1
GUIDELINESWHATS NEW AND WHATS NOT

• WWW.DIABETES.CA/FOR-PROFESSIONALS/2008-CPG
• WWW.HYPERTENSION.CA/CHEP
• WWW.LIPIDNURSE.CA
• WWW.CHRC.NET

2
A Man is as Old as His Arteries
Dr Thomas Sydenham (1624-89)
3
A.C. A HEALTH PROFESSIONAL

• 64 YEAR OLD MALE IN 2001
• 238 LB
• DIABETIC SINCE 1999
• SMOKES 1 PPD
• BP 158/104
• BROTHER HAD MI AT AGE 54 SISTER MI AGE 50 FATHER
  DIED AGE 55
• LIPIDS ELEVATED
• STRESS ON WELLBUTRIN
• ATYPICAL CHEST PAIN NEGATIVE STRESS TEST
• IMPAIRED VIBRATION SENSE IN FEET

4
CVD Realities

• CVD represents the single greatest health threat
  worldwide1
• Claims a life every 34 seconds in the US2
• Claims more lives than the next 5 leading causes
  of death3
• CVD prevalence will continue to rise as
  urbanization increases in developing areas of the
  world4

1. The World Health Report 2003 shaping the
future. Geneva, Switzerland World Health
Organization. 2003. 2. Arias E, Smith BL. Nat
Vital Stat Rep. 2003511-44,48. Available at
www.cdc.gov/nchs/data/nvsr/nvsr51/nvsr51_05.pdf.
3. American Heart Association. Heart Disease and
Stroke Statistics 2004 Update. 2003. 4. Reddy
KK, et al. Asia Pacific J Clin Nutr.
20021198-103.
5
Hospitalizations for CVD in Canada Actual and
Projected, 1971-2016
2006
Source LCDC, Health Canada
6
The Vast Majority Of Hypertensive Patients Also
Have Another Risk Factor
? Risk factors ? Global CV risk
Rantala AO, Kauma H, Ljilja M, et al. J Intern
Med. 1999245163-174. Wannamethee SG, Shaper
AG, Durrington PN, et al. J Hum Hypertens. 1998
12735-741.
7
Evolution in the Understanding of CVD
Traditional CVD Perspective
Blood Pressure
Multiple Independent Risk Factors
Poulter N. Am J Hypertens. 19991292S-95S.
8
INTERHEART Impact of Multiple Risk Factors on
CAD Risk
2.9
2.4
1.9
3.3
13.0
42.3
68.5
182.9
333.7
512
256
128
64
32
16
Odds ratio for 1st MI (99 CI)
8
4
2
1
ApoB
All risk
HTN
All 4
Smk
DM
-
123
All 4
All 4
factors
ApoA1
(1)
(2)
(3)
Obes
Ps
(4)
Note odds ratio plotted on a doubling scale.
Smk smoking DM diabetes HTN hypertension
ApoB apolipoprotein B ApoA1 apolipoprotein
A-1 Obes obesity Ps psychosocial factors
Yusuf S, et al. Lancet. 2004364937-952.
9
Number of CVD Risk Factors, per Health Region,
with a Prevalence Greater than the National
Average, 2000/01
Vancouver
P.E.I
Montreal
Maritimes
Southeast Ontario
Central/Southwest Ontario
Source Canadian Cardiovascular Outcomes Research
Team,Statistics Canada Canadian Community Health
Survey 2000/01.
10
MRFIT Combined Effects of SBP and Total
Cholesterol on CHD Mortality
n 316 099
Deaths/10000 p-y
Cholesterol (mmol/L)
SBP (mmHg)
Multiple Risk Factor Intervention Trial Research
Group. Arch Intern Med. 199215256-64.
11
ASCOT-LLA Primary End Point Nonfatal MI and
Fatal CHD
Originally planned length of trial 5 years
Actual length of trial median 3.3 years
Lipitor 10 mg (n 5168) Placebo (n 5137)
36relative riskreduction in nonfatal MI and
fatal CHD
Cumulative Incidence ()
(P.0005)
HR 0.64 (0.50-0.83)
5.0
Years
Sever PS et al, for the ASCOT Investigators.
Lancet. 20033611149-1158.
12
Antihypertensive Therapy and Statin Therapy is
Effective at Reducing CV Risk

• Antihypertensive therapy reduces the risk of
• Statin therapy reduces the risk of

35-40
20-25
Stroke
MI1
27-29
23-36
Stroke
CHD2
1. Chobanian AV, et al. JAMA. 20032892560-2572.
2. Jacobson TA, et al. Arch Intern Med.
19981581977-1989.
13
2006 CHEP Recommendations Impact
of ASCOT-LLA
According to CHEP 2006 recommendations, statins
are recommended in hypertensive patients with
established atherosclerotic disease or with at
least 3 cardiovascular risk factors such as
Previous stroke or TIA LVH ECG
abnormalities Microalbuminuria or
proteinuria  Peripheral vascular disease
Male 55 y or older Smoking Type 2
diabetes Total-C/HDL-C ratio of 6 or higher
Premature family history of CV disease
ASCOT-LLA Lancet 20033611149-58. 2006 Canadian
Hypertension Education Program Recommendations
14
CARDS - Effect of Atorvastatin on the Primary End
Point Major CV Events Including Stroke
15
Relative Risk Reduction 37 (95 CI
17-52) p.001 NNT 27 patients over 4 years to
prevent one major first CV event
Placebo 127 events
10
Cumulative hazard ()
Atorvastatin 83 events
5
0
Years
0
1
2
3
4
4.75
305
651
1022
1306
1351
Placebo
1410
328
694
1074
1361
1392
Atorva
1428
gtgtMore Outcomes Results
NNT number needed to treat CI confidence
interval
Colhoun HM, Betteridge DJ, Durrington PN, et al.
Lancet. 2004364685-696.
15
Most Diabetes is not Diagnosed
1.5 million Canadians have diabetes mellitus
Frequency of diagnosed and undiagnosed diabetes
and IGT by age (U.S. data)
40
IGT
35
Undiagnosed diabetes
Diagnosed diabetes
30
25
of population
20
15
10
5
0
20-34
35-44
45-54
55-64
65-74
Age
Leiter et al. Diabetes Care 2001241038-43.
Adapted from Centers for Disease Control and
Prevention. Surveillance report Nov. 1998
American Diabetes Association. Diabetes facts and
figures 1997.
16
HbA1c Strongly Predicts CVD Events in the Absence
of Known Diabetes
lt 5 5-5.4 5.5-5.9 6-6.4
6.5-6.9 gt 7.0 known
diabetes
European Prospective Investigation into Cancer in
Norfolk 4662 M/5570 F 45-79 y 7 yr follow-up
(806 CVD events, 506 deaths) Ann Intern Med
2004141413-20
17
Canadian Diabetes Association Glycemic Targets
HbA1C glycosylated hemoglobin FPG fasting
plasma glucose
CDA CPG Expert Committee. Can J Diabetes
200327(Suppl 2)S1-S152.
18
Natural History of Diabetes
Disability
Complication
Onset of Diabetes
Atherosclerosis
Diabetes - Hyperglycemia
Type 1
Retinopathy Nephropathy Neuropathy
Blindness ESRD Amputation Coronary Heart Disease
Diagnosis
Death
Genetic Susceptibility Environmental Factors
Type 2
IGT
Diabetes - Hyperglycemia
Atherosclerosis
Insulin Resistance Hyperinsulinemia HDL
Cholesterol Triglycerides Hypertension
19
The deathly impact of giving up on A1C control
Microvascular complications
Macrovascular complications
Stroke, dementia
Retinopathy
12 of all new cases of blindness
Heart disease
Nephropathy
gt40 of new cases of end-stage renal disease
(ESRD)
Diagnosed in 37.2 of patients with diabetes gt35
years old
Neuropathy
PVD
30 to 40reduction
14 to 30reduction
1 reductionA1C
Benjamin SM et al. JAMA 2003 290(23)3060-3.
National Society to Prevent Blindness. Vision
Problems in the U.S. A Statistical Analysis.
New York, NY National Society to Prevent
Blindness, 1980 Perneger TV et al. Ann Intern
Med 1994 121(12)912-8 Stratton IM et al. BMJ
2000 321(7258)405-12 The Diabetes Control and
Complications Trial Research Group. N Engl J Med
1993 329(14)977-86.
20
Glycemic Control and Disease Burden
Treatment strategies may not be aggressive enough
to control all patients, particularly those who
have had the disease the longest.
100
90
80
67
62
62
70
53
52
60
Patients ()
44
42
50
42
31
32
40
32
21
25
30
22
17
20
10
0
2 years
3 - 5 years
6 - 9 years
10 - 14 years
15 years
Macrovascular complications
Microvascular complications
A1C 7
21
CDA Guidelines Cardiorenal Prioritization

• In All High-risk Patients
• ACE inhibitor
• ASA
• Lipid control
• BP control
• Also as required
• Glycemic control
• Lifestyle
• Smoking cessation

1. Vascular Protection
2. Hypertension Control
3. Control of Nephropathy
22
Achieving a Lower BP Associated with Reduced
Mortality (UKPDS 36)
All-cause Mortality
4
P lt .0001
Hazard Ratio
1
12 decrease per 10 mm Hg reduction in systolic
blood pressure
0.5
110
120
130
140
150
160
170
Updated Mean Systolic Blood Pressure (mm Hg)
Adler AI. BMJ. 2000321412-419.
23
Decreased Risk of Diabetes-related Complications
Associated with a 1 Decrease in A1C
Any diabetes- related end point
Diabetes- related death
All- cause mortality
Peripheral vascular disease
Micro- vascular disease
Myocardial infarction
Cataract extraction
Stroke
Percentage Increase in Relative Risk
Corresponding to a 1 Rise in A1C
12
14
14

19

21
21




37
Lower extremity amputation or fatal peripheral
vascular disease P .035 P lt .0001
43


Adapted from Stratton IM, et al. UKPDS 35. BMJ.
2000321405412.
24
Diabetes, Glucose, and CV Disease

• Diabetes (DM) is an established risk factor for
  CVD
• In DM, higher glucose levels/A1C predict higher
  CV risk

Fatal Nonfatal Stroke
Fatal Nonfatal MI
10
12 rise per 1 rise in A1C
14 rise per 1 rise in A1C
Hazard Ratio
1
P lt .035
P lt .0001
0.5
Amputation/Death from PVD
Heart Failure
43 rise per 1 rise in A1C
10
16 rise per 1 rise in A1C
Hazard Ratio
1
P lt .021
P lt .0001
0.5
10
6
5
7
8
9
6
5
7
8
9
10
Stratton IM, et al. BMJ. 2000321405-412.
25
The Greater the LDL-C Reduction, the Better the
Effect on Coronary Artery Disease Risk
Adapted from Kastelein JJ. Atherosclerosis
1999143(Suppl 1)S17-S21.
26
FRS 10-Year Risk
How accurate is Risk prediction in This group?
Low Risk
?
Medium Risk
?
High Risk
27
Beyond Framingham

• Genetic risk
• hsCRP
• HbA1c
• Lp(a)
• Apo B
• Exercise capacity
• Noninvasive assessment of atherosclerosis

28
Exercise Capacity and 8 yr Risk of Death in 5,721
Women (52 11 yr) Circulation 20031081554-9.
RR
29
10 yr Risk of CAD for Subjects in any Risk
Category may be Modified on Basis of GXT
1 5
10 15
20
Framingham 10 yr normal GXT abnormal GXT
risk of coronary event
Greenland P NEJM 2003349465-73 after Gibbons
LW Am J Cardiol 20038653-3
30
FRS 10-Year Risk
Multiply calculated 10 year risk by 2 if family
history of premature CAD
Low Risk
?
Medium Risk
?
High Risk
31
hsCRP Adds Prognostic Information at all Levels
of LDL-C and at all Levels of the Framingham Risk
Score
Real 10 year risk for patients in the
intermediate risk category varies by 2-fold
dependent on plasma hsCRP
lt1.0
1.0-3.0
gt3.0
lt1.0
1.0-3.0
gt3.0
C-Reactive Protein (mg/L)
C-Reactive Protein (mg/L)
25
3
20
2
15
Relative risk
Multivariable relative risk
10
1
5
0
0
0-1
2-4
5-9
10-20
130-160
lt130
gt160
Framingham estimate of 10-year risk ()
LDL cholesterol (mg/dL)
N Engl J Med. 20023471557.
32
Prevalence of Atherosclerosis by Donor Age
100
EEM Area13.2 mm2
85
80
71
60
60
Prevalence ofAtherosclerosis ()
5.07mm2
37
40
17
20
0
Atheroma Area 8.13 mm2
lt20
20-29
30-39
40-49
50
32-year-old Female
Donor Age (Years)
Tuzcu EM, et al. Circulation. 20011032705-2710.
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A.C.--2008

• HAD CATARACT SURGERY
• BP200/98
• COVERSYL 4 MG INCREASED TO 8MG
• EXAM REVEALS 204LB AND AORTIC OUTFLOW MURMER
  RADIATING INTO R CAROTID A.
• DEPRESSED (S.A.D.) ON CIPLALEX
• FBS 14 A1C 9.9 ALB/CREAT 110 NORMALlt2
• CHOL 5.36 TG 2.52 HDL 1.07 LDL 3.14
• ECHO SHOWED AORTIC SCLEROSIS
• CXRTHORACIC SPINE OSTEOPHYTES
• CAR USG MILD PLAQUE

40
Part 2 Recommendations for Hypertension Treatment
41
Key CHEP messages for the management of
hypertension

• Assess blood pressure at all appropriate visits.
• Encourage people with hypertension to use
  approved devices and proper technique to measure
  blood pressure at home.
• Ensure people with hypertension are screened for
  diabetes (and vice versa). Treat hypertension in
  people with diabetes with a combination of
  lifestyle changes and pharmacotherapy to control
  blood pressure to less than 130/80 mmHg. Many
  require use of three or more antihypertensive
  drugs including diuretics to achieve blood
  pressure targets.
• Assess and manage overall cardiovascular risk in
  all people with hypertension including smoking,
  dyslipidemia, dysglycemia, abdominal obesity,
  unhealthy eating and physical inactivity.
• Sustained lifestyle modification is the
  cornerstone for the prevention and management of
  hypertension and cardiovascular disease (CVD).
• Treat blood pressure to less than 140/90 mmHg in
  most people and to less than 130/80 mmHg in
  people with diabetes or chronic kidney disease.
  More than one drug is usually required.

42
Whats New for 2009The Hypertensive Diabetic

• Patients with diabetes are at high cardiovascular
  risk
• Up to 80 of diabetic patients die of
  cardiovascular disease
• Most patients with diabetes have hypertension
• Between 35 and 75 of diabetic complications have
  been attributed to hypertension.
• Treatment of hypertension in patients with
  diabetes reduces total mortality, myocardial
  infarction, stroke, retinopathy and progressive
  renal failure rates.
• More intensive reduction in blood pressure
  reduces major cardiovascular events and total
  mortality by 25

Treating hypertension in the diabetic patient
reduces death and disability and reduces health
care system costs TARGET lt130 systolic and lt80
mmHg diastolic
43
Whats New for 2009The Hypertensive Diabetic

• 2/3rds of hypertensive diabetic patients have
  uncontrolled hypertension (gt 130/80 mmHg)
• There is underutilization of diuretic therapy in
  treating hypertension in diabetic patients. In
  general a diuretic is required for blood pressure
  control in multi drug regimes.
• A combination of lifestyle changes and 3 or more
  medications are often required.
• More intensive reduction in blood pressure in the
  hypertensive diabetic is one a few medical
  interventions where the cost of treatment is less
  than the cost of the complications prevented

Treating hypertension in the diabetic patient
reduces death and disability and reduces health
care system costs TARGET lt130 systolic and lt80
mmHg diastolic
44
Whats New for 2009

• Increased age on its own should not be a
  consideration in determining the need for
  antihypertensive drug therapy. Drug therapy for
  the elderly should be based on the same criteria
  as in younger adults however caution should be
  exercised in elderly patients who are frail or
  have postural hypotension.

N Engl J Med 20083581887-98
45
Whats New for 2009

• The combination of an ACE inhibitor with an ARB
  is not recommended in patients with
• hypertension without compelling indications,
• coronary artery disease who do not have heart
  failure,
• prior stroke,
• non proteinuric chronic kidney disease or
• diabetes mellitus without micro albuminuria

N Engl J Med 20083581547-59 Lancet 2008 372
54753
46
Whats New for 2009

• The use of combination of ACE inhibitor with an
  ARB should only be considered in selected and
  closely monitored people with advanced heart
  failure or proteinuric nephropathy.

47
2009 Canadian Hypertension Education Program
(CHEP)

• Important messages from past recommendations
• IMPORTANT ROLE FOR HOME MEASUREMENT OF BLOOD
  PRESSURE
• Encourage hypertensive patients to use an
  approved blood pressure measuring device and use
  proper technique to assess blood pressure at
  home.
• Home measurement can help to confirm the
  diagnosis of hypertension, improve blood pressure
  control, reduce the need for medications,
  identify patients with white coat and masked
  hypertension and improve medication adherence

48
2009 Canadian Hypertension Education Program
(CHEP)

• Important messages from past recommendations
• High dietary sodium is estimated to increase
  blood pressure in the Canadian population to the
  extent that 1,000,000 Canadians meet the
  diagnostic criteria for hypertension who would
  otherwise have normal blood pressure
• Most of the sodium in Canadian diets comes from
  processed foods and restaurants.
• Pizza, breads, soups and sauces usually have high
  amounts of sodium
• Patient information on how to achieve a reduced
  sodium diet can be found at www.hypertension.ca
• Aim to reduce sodium intake to less than 2300
  mg/day to prevent and control hypertension

49
Usual blood pressure threshold values for
initiation of pharmacological treatment of
hypertension
I. Indications for Pharmacotherapy
50
I. Indications for Pharmacotherapy

• In low risk patients with stage 1 hypertension
  (140-159/90-99 mmHg) lifestyle modification can
  be the sole therapy.
• Over 90 of Canadians with hypertension have
  other risk factors and pharmacotherapy should be
  considered in these patients if blood pressure
  remains equal to or above 140/90 mmHg with
  lifestyle modification.
• In particular many younger hypertensive Canadians
  with multiple cardiovascular risks are currently
  not treated with pharmacotherapy. Health care
  professionals need to be alert to this important
  care gap and recommend pharmacotherapy.
• Patients with target organ damage (e.g. left
  ventricular hypertrophy) are recommended to be
  treated with pharmacotherapy if blood pressure is
  equal to or above 140/90 mmHg
• Patients with diabetes or chronic kidney disease
  should be considered for pharmacotherapy if the
  blood pressure is equal or over 130/80 mmHg

51
Blood pressure target values for treatment of
hypertension
II. Goals of Therapy
52
II. Goals of Therapy

• To optimally reduce cardiovascular risk reduce
  the blood pressure to specified targets.
• This usually requires two or more drugs and
  lifestyle changes
• The systolic target is more difficult to achieve
  however controlling systolic blood pressure is as
  important if not more important than controlling
  diastolic blood pressure

53
Lifestyle Recommendations for Prevention and
Treatment of Hypertension

• To reduce the possibility of becoming
  hypertensive,
• Reduce sodium intake to less than 2300 mg / day
• Healthy diet high in fresh fruits, vegetables,
  low fat dairy products, dietary and soluble
  fiber, whole grains and protein from plant
  sources, low in saturated fat, cholesterol and
  sodium in accordance with Canada's Guide to
  Healthy Eating.
• Regular physical activity accumulation of 30-60
  minutes of moderate intensity cardiorespiratory
  activity (e.g. a brisk walk)
• 4-7 days/week in addition to routine activities
  of daily living
• Low risk alcohol consumption (2 standard
  drinks/day and less than 14/week for men and less
  than 9/week for women)
• Maintenance of ideal body weight (BMI 18.5-24.9
  kg/m2)
• Waist Circumference
  Men Women
• - Europid, Sub-Saharan African, Middle Eastern
  lt94 cm lt80 cm
• - South Asian, Chinese lt90 cm lt80 cm
• - Smoke free environment

54
Sodium Meta-analyses

• Hypertensives
• Reduction of BP
• 5.1 / 2.7 mmHg with a average reduction of 1800
  mg sodium/day
• 7.2/3.8 mmHg with a average reduction of 2300 mg
  sodium/day
• Normotensives
• Reduction of BP
• 2.0 / 1.0 mmHg with a average reduction of sodium
  1700 mg/day
• 3.6/1.7 mmHg with a average reduction of 2300
  mg/day sodium

The Cochrane Library 200631-41
55
Lifestyle Recommendations for Hypertension
Physical Activity
Should be prescribed to reduce blood pressure
Frequency - Four to seven days per week
Type cardiorespiratory activity - Walking,
jogging - Cycling - Non-competitive swimming
Exercise should be prescribed as adjunctive to
pharmacological therapy
56
Lifestyle Recommendations for Hypertension
Weight LossHeight, weight, and waist
circumference (WC) should be measured and body
mass index (BMI) calculated for all adults.
CMAJ 20071761103-6
57
Impact of Lifestyle Therapies on Blood Pressure
in Hypertensive Adults
Applying the 2005 Canadian Hypertension Education
Program recommendations 3. Lifestyle
modifications to prevent and treat hypertension
Padwal R. et al. CMAJ ? SEPT. 27, 2005 173 (7)
749-751
58
V. Choice of Pharmacological Treatment
Uncomplicated
Associated risk factors? or Target organ
damage/complications? or Concomitant
diseases/conditions?
59
V. Treatment of Adults with Systolic/Diastolic
Hypertension without Other Compelling Indications
TARGET lt140/90 mmHg
INITIAL TREATMENT AND MONOTHERAPY
Lifestyle modification therapy
A combination of 2 first line drugs may be
considered as initial therapy if the blood
pressure is gt20 mmHg systolic or gt10 mmHg
diastolic above target
Thiazide
Beta-blocker
Long-acting CCB

• BBs are not indicated as first line therapy for
  age 60 and above

ACEI, ARB and direct renin inhibitors are
contraindicated in pregnancy and caution is
required in prescribing to women of child bearing
potential
60
V. Considerations Regarding the Choice of
First-Line Therapy

• Use caution in initiating therapy with 2 drugs in
  whom adverse events are more likely (e.g. frail
  elderly, those with postural hypotension or who
  are dehydrated).
• ACE inhibitors, renin inhibitors and ARBs are
  contraindicated in pregnancy and caution is
  required in prescribing to women of child bearing
  potential.
• Beta adrenergic blockers are not recommended for
  patients age 60 and over without another
  compelling indication.
• Diuretic-induced hypokalemia should be avoided
  through the use of potassium sparing agent if
  required.
• The use of combination of ACE inhibitor with a
  ARB should only be considered in selected and
  closely monitored people with advanced heart
  failure or proteinuric nephropathy.
• ACE-I are not recommended (as monotherapy) for
  black patients without another compelling
  indication.

61
V. Add-on Therapy for Systolic/Diastolic
Hypertension without Other Compelling Indications
If partial response to monotherapy
If blood pressure is still not controlled, or
there are adverse effects, other classes of
antihypertensive drugs may be combined (such as
alpha blockers or centrally acting agents).
62
Drug Combinations

• When combining drugs, use first-line therapies.
• Two drug combinations of beta blockers, ACE
  inhibitors and angiotensin receptor blockers have
  not been proven to have additive hypotensive
  effects. Therefore these potential two drug
  combinations should not be used unless there is a
  compelling (non blood pressure lowering)
  indication
• Combinations of an ACEI with an ARB do not reduce
  cardiovascular events more than the ACEI alone
  and have more adverse effects therefore are not
  generally recommended

63
Drug Combinations contd

• Caution should be exercised in combining a non
  dihydropyridine CCB and a beta blocker to reduce
  the risk of bradycardia or heart block.
• Monitor serum creatinine and potassium when
  combining K sparing diuretics, ACE inhibitors
  and/or angiotensin receptor blockers.
• If a diuretic is not used as first or second line
  therapy, triple dose therapy should include a
  diuretic, when not contraindicated.

64
Treatment Algorithm for Isolated Systolic
Hypertension without Other Compelling Indications
TARGET lt140 mmHg
INITIAL TREATMENT AND MONOTHERAPY
Lifestyle modification therapy
Thiazide diuretic
ARB
Long-acting DHP CCB
65
V. Summary Treatment of Isolated Systolic
Hypertension without Other Compelling Indications
TARGET lt140 mmHg
Lifestyle modification therapy
Thiazide diuretic
ARB
Long-acting DHP CCB
Dual therapy

• CONSIDER
• Nonadherence
• Secondary HTN
• Interfering drugs or lifestyle
• White coat effect

If blood pressure is still not controlled, or
there are adverse effects, other classes of
antihypertensive drugs may be combined (such as
ACE inhibitors, alpha blockers, centrally acting
agents, or nondihydropyridine calcium channel
blocker).
Triple therapy
66
XII. Treatment of Hypertension in association
with Diabetes Mellitus Summary
Threshold equal or over 130/80 mmHg and TARGET
below 130/80 mmHg
A combination of 2 first line drugs may be
considered as initial therapy if the blood
pressure is gt20 mmHg systolic or gt10 mmHg
diastolic above target
ACE Inhibitor or ARB
1. ACEInhibitor or ARB or 2. Thiazide diuretic or
DHP-CCB
without Nephropathy
gt 2-drug combinations
Monitor serum potassium and creatinine carefully
in patients with CKD prescribed an ACEI or
ARB Combinations of an ACEI with an ARB are
specifically not recommended in the absence of
proteinuria
More than 3 drugs may be needed to reach target
values for diabetic patients If Creatinine over
150 µmol/L or creatinine clearance below 30
ml/min ( 0.5 ml/sec), a loop diuretic should be
substituted for a thiazide diuretic if control of
volume is desired
67
XIII. Treatment of Hypertension for Patients Who
Use Tobacco
68
XIV. Vascular Protection for Hypertensive
Patients Statins

• In addition to current Canadian recommendations
  on management of dyslipidemia, statins are
  recommended in high-risk hypertensive patients
  with established atherosclerotic disease or with
  at least 3 of the following criteria

ASCOT-LLA Lancet 20033611149-58
69
XIV. Vascular Protection for Hypertensive
Patients ASA
Consider low dose ASA
Caution should be exercised if BP is not
controlled.
70
Adherence to anti-hypertensive management can be
improved by a multi-pronged approach

• Assess adherence to pharmacological and
  non-pharmacological therapy at every visit
• Teach patients to take their pills on a regular
  schedule associated with a routine daily activity
  e.g. brushing teeth.
• Simplify medication regimens using long-acting
  once-daily dosing
• Utilize fixed-dose combination pills
• Utilize unit-of-use packaging e.g. blister
  packaging

71
NEW PATIENT RESOURCES FOR HYPERTENSION ON LINE

• www.heartandstroke.ca/BP
• To monitor home blood pressure and encourage self
  management of lifestyle
• www.hypertension.ca
• To access up to date downloadable patient
  information on hypertension

72
ACNOV 2008

• OSA TRIED CPAP
• 220 LB
• A1C 7.7 CHOL 2.62 TG 1.39 HDL 0.9 LDL 1.13
  RR2.3
• MEDS ASA 81 , AVALIDE 300/25 , NORVASC 10 MG ,
  TENORMIN 50 MG ,SPIRONOLACTONE 50 MG, CRESTOR 20
  MG ,DIAMICRON MR 60 MG , METFORMIN 500 MG BID ,
  OMEGA 3-6-9
• BP STILL 170/80
• CT R/O RAS EXTENSIVE AORTO-ILIAC CALCIFICATION

73
A.C.

• U/A TRACE BLOOD
• MICROALBUMINURIA 2279 IN JAN
• FELL TO 522 IN JUNE
• BY DEC 2063
• EXTENSIVE NEPHROLOGY WORK UP HAD REVEALED
  INCREASED IGA
• BP 230/130
• ADMITTED

74
A.C.

• COUGH WITH ACE INHIBITORS
• DEPRESSION WITH BETA BLOCKERS
• PEDAL EDEMA WITH CALCIUM CHANNEL BLOCKERS
• RESPONDED TO DIURETICS AND MINOXIDIL
• ECHO SHOWED MARKED LVH AND DILATED LEFT ATRIUM
• SEEN AGAIN BY NEPHROLOGY

75
A.C.

• KIDNEY BIOPSY RE IGA AND PROTEINURIA
  DISPROPORTIONATE
• DEVELOPED BLADDER CLOTS CAUSING RETENTION
• TREATED WITH CBI
• MEDS ASA 81 MG , ALDACTAZIDE 25/25 OD ,
  ALISKIREN 300 MG OD , AVAPRO 300 MG BID ,
  ISOPTIN SR 240 MG BID , MINOXIDIL 10 MG BID ,
  GLICLAZIDE 60 MG OD , METFORMIN 500 MG BID ,
  CRESTOR 20 MG OD , PREVACID 30 MG OD

76
A.C.

• OBSERVED BY COLLEAGUES 2 WEEKS LATER TO APPEAR
  UNWELL
• PERSUADED TO HAVE ECG
• NEW ST CHANGE SEEN
• ADMITTED TROPONIN BORDERLINE
• ECHO SHOWED NEW INFERIOR HYPOKINESIS
• HB 88----130 ON DISCHARGE
• TREATED AS ACS

77
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78
(No Transcript)
79
Risk Stratification and Treatment Plan for
Patients Presenting with Non-ST-Elevation Acute
Coronary Syndrome Atlantic Canada Consensus
ER and In Hospital Protocol
LOW RISK 30-day death/MI lt2
HIGH RISK 30-day death/MI 12-30
VERY HIGH RISK 30-day death/MI 30
INTERMEDIATE RISK 30-day death/MI 4-8
Catheterization Time lt 24 hrs
Catheterization Time 24-72 hrs
Catheterization Time lt 7 days
80
A.C.

• ENDOSCOPY/ COLONOSCOPY NEGATIVE
• USG SHOWED LARGE PERINEPHRIC HEMATOMA
• NO ANTICOAGULATION ALLOWED BY NEPHROLOGY UNTIL
  RESOLUTION SEEN.
• 10 DAYS OF OBSERVATION
• FINALLY SENT TO ST. J.R.H.
• 85 PROX RCA MID 100 RCA , 70-80 OM1 , RAMUS
  80 , 80 D1 , 70 D2 , 70 LAD.
• ACCEPTED FOR IN HOUSE SURGERY

81
A.C.

• CABG X SIX
• MEDIASTINITIS
• KLEBSIELLA SEPTIC SHOCK
• IMPROVED WITH ANTIBIOTICS
• C-DIFFICILE ENTEROCOLITIS
• AFTER 3 WEEKS DISCHARGED UNDER EMH FOR HOME
  ANTIBIOTICS
• AFTER 24 HOURS HOME PICC LINE BLOCKED

82
Risk Stratification and Treatment Plan for
Patients Presenting With Non-ST- Elevation ACS
Atlantic Canada Consensus
Discharge Management

• MEDICAL THERAPY CONTINUED AT DISCHARGE
• ASA (80-325 mg od) ? Clopidogrel (75mg od for
  9 months to 1 year)
• Lipid lowering agent ? ACE Inhibitor
• Beta blocker - discretionary

• PATIENT EDUCATION/REHABILITATION
• No driving for 1 month for private car ?
  Resumption of daily activities
• Warning signs for future event ? Resumption of
  sexual activity
• What to do if chest pain occurs ? Exercise
  Program
• When to call 911 ? How to take medications

• LIFESTYLE/RISK FACTOR MANAGEMENT
• Smoking Cessation
• Achieve Ideal body weight
• Heart Healthy Diet
• Waist Circumference lt36(male), 33(women)
• Control Diabetes with HbA1c lt10 above normal
  limit
• Exercise Regularly

• FOLLOW-UP TESTING
• Control blood pressure, monitor BMI, waist
  circumference
• Check cholesterol, LFTs, Fasting glucose
• Check HbA1C if diabetic
• Assess ejection fraction-ECHO/WMS (RNA)/or
  Ventriculogram if not done in hospital

83
Many Patients Fail to Persist With Prescribed
Treatments for BP and Lipids

• High BP High Lipids
• Failure to fill a 2nd prescription(for the same
  or any othermedication for that indication)1
  15 10
• Failure to persist withpharmacotherapy
• 12 months after 1st prescription1 38 34
• 18 months after 1st prescription2 49 47

1. Hertz RP, et al. Pharmacoepidemiol Drug Saf.
200312S75. 2. Pfizer facts. High cholesterol
and high blood pressure in the United States
workforce, 2002.
84
Adherence Decreases as the Number of Daily Doses
Increases

• Frequency of regimen No. of Mean
  dose-taking(doses/day) reports compliance
• 1 29 79
• 2 32 69
• 3 13 65
• 4 11 51
• All regimens 85 71

Some studies reported data for gt1 dosing
regimen. Claxton AJ, et al. Clin Ther.
2001231296-1310.
85
Refocusing Management From Individual Risk
Factors to the Patients Overall Global Risk
Adapted from WHO/ISH Recommendations on
Hypertension. Journal of Hypertension 2003, Vol
21 No 6
86
Combined Treatment of Major Risk Factors Would
Significantly Impact CHD and Stroke
BP blood pressure CHD coronary heart
disease. Wald NJ, et al. BMJ. 20033261419.
87
Simultaneous Initiation of Therapies Improves
Patient Adherence
100
80
60
Patients Adherent to Both AHD and LRD Therapies (
)
40
20
0
0
2
4
6
8
10
12
Months From Index
AHD antihypertensive drug therapy LRD
lipid-regulating drug therapy. Adapted from
Schwartz JS, et al. Poster presented at 52nd
Annual Scientific Session of the American College
of Cardiology March 30-April 2, 2003 Chicago,
Ill.
88
Future Paradigm
Unified Treatment Guidelines

• Aligned on strategies to reduce overall CV risk

CWG
CDA
CHEP
SOLIDDE Some Opinion Leaders in the
Development, Dissemination, and Evaluation of
Cardiovascular Health Recommendation in Canada
Group
89
JUPITER study design
No history of CAD men 50 yrs women 60
yrs LDL-C lt130 mg/dL CRP 2.0 mg/L
Rosuvastatin 20 mg (n8901)
Placebo run-in
Placebo (n8901)
16
24
30
413
VisitWeek
Final
6-monthly
Lead-in/eligibility
Lipids CRP Tolerability
Lipids CRP Tolerability HbA1C
Randomisation
Lipids CRP Tolerability
Median follow-up 1.9 years
CADcoronary artery disease LDL-Clow-density
lipoprotein cholesterol CRPC-reactive protein
HbA1cglycated haemoglobin
Ridker P et al. N Eng J Med 2008359 2195-2207
These slides have been supplied, on request, by
AstraZeneca Medical Affairs. For complete
therapeutic and safety information please consult
the CRESTOR Product Monograph.
90
JUPITER - Study Endpoints

• Primary Endpoint
• Time to the first occurrence of a major
  cardiovascular event, composite of
• cardiovascular death
• Stroke
• MI
• unstable angina
• arterial revascularisation
• Secondary Endpoints
• total mortality
• non-cardiovascular mortality
• development of diabetes mellitus
• development of venous thromboembolic events
• bone fractures
• discontinuation of study medication due to
  adverse effects.

Ridker PM. Circulation 2003 108 22922297
91
JUPITER - Major exclusion criteria

• Current use of statins or other lipid-lowering
  therapies
• Current use of post menopausal hormone
  replacement therapy
• Prior history of cardiovascular or
  cerebrovascular events, such as MI, unstable
  angina, prior arterial revascularisation or
  stroke, or CHD-risk equivalents
• Chronic inflammatory condition, such as severe
  arthritis, lupus or inflammatory bowel disease
  and/or treatment with immunosuppressants
• Uncontrolled
• hypertension SBP gt 190 mmHg or DBP gt 100 mmHg
• hypothyroidism TSH gt 1.5 x ULN
• CK ?3 x ULN
• Serum creatinine gt 2.0 mg/dL
• Evidence of hepatic dysfunction (ALT gt 2 x ULN)
• History of prior malignancy, alcohol or drug abuse

CHD coronary heart disease CK creatinine
kinase ULN upper limit of normal SBP
systolic blood pressure DBP diastolic blood
pressure
Ridker P et al. N Eng J Med 2008359 2195-2207
Ridker PM. Circulation 2003 108 22922297
These slides have been supplied, on request, by
AstraZeneca Medical Affairs. For complete
therapeutic and safety information please consult
the CRESTOR Product Monograph.
92
JUPITER - Patient Flow
89,890 subjects screened 17,802 randomised
Rosuvastatin 20mg n8,901
Placebo n8,901
Lost to follow up n44
Lost to follow up n37
Completed study n8,857
Completed study n8,864
Ridker P et al. N Eng J Med 2008359 2195-2207
93
JUPITER - Baseline characteristics
Rosuvastatin Placebo n8901 n8901
Age (years) 66 (60-71) 66 (60-71) Male sex ()
61.5 62.1 Race () White 71.4 71.1 Black 12.4
12.6 Hispanic 12.6 12.8 Other 3.6 3.5 BMI
(kg/m2) 28.3 (25.3-32.0) 28.4 (25.3-32.0) Systoli
c BP (mmHg) 134 (124-145) 134 (124-145) Diastoli
c BP (mmHg) 80 (75-87) 80 (75-87)
All values are median (interquartile range) or N
().
Ridker P et al. N Eng J Med 2008359 2195-2207
94
JUPITER - Baseline laboratory parameters
Rosuvastatin Placebo n8901 n8901
Total cholesterol (mmol/L) 4.81 (4.34-5.17) 4.78
(4.37-5.15) LDL cholesterol (mmol/L) 2.79
(2.43-3.08) 2.79 (2.43-3.08) HDL cholesterol
(mmol/L) 1.27 (1.03-1.55) 1.27
(1.03-1.55) Triglycerides (mmol/L) 1.33
(0.96-1.91) 1.33 (0.97-1.91) hsCRP (mg/L) 4.2
(2.8-7.1) 4.3 (2.8-7.2) Glucose (mmol/L) 5.2
(4.8-5.7) 5.2 (4.9-5.7) HbA1c() 5.7
(5.4-5.9) 5.7 (5.5-5.9) Glomerular filtration
rate, (ml/min/1.73m2) 73.3 (64.6-83.7) 73.6
(64.6-84.1)
For hsCRP, values are the average of the values
obtained at two screening visits
All values are median (interquartile range) or N
().
Ridker P et al. N Eng J Med 2008359 2195-2207
95
JUPITER - Medical History
Medical History Rosuvastatin
Placebo n8901
n8901
Current smoker () 15.7 16.0 Family history
CHD () 11.2 11.8 Metabolic syndrome
() 41.0 41.8 Aspirin use () 16.6 16.6
Family history of premature coronary heart
disease (CHD) defined as first degree relative
with CHD at age lt 55 yrs (male), lt 65 yrs
(female) Metabolic syndrome defined according
to consensus criteria of American Heart
Association and the National Heart, Lung, and
Blood Institute
Ridker P et al. N Eng J Med 2008359 2195-2207
96
JUPITER - Primary Endpoint Time to first
occurrence of a CV death, non-fatal stroke,
non-fatalMI, unstable angina or arterial
revascularisation
Hazard Ratio 0.56 (95 CI 0.46-0.69) Plt0.00001
Placebo
0.08
0.06
Cumulative Incidence
Rosuvastatin 20 mg
0.04
NNT for 2 yrs 95 5 yrs 25
0.02
0.00
0
1
2
3
4
5
Years
Number at risk Rosuvastatin 8901 8412
3893 1353
538 157 Placebo 8901 8353
3872 1333
531 174
Extrapolated figure based on Altman and Andersen
method
Ridker P et al. N Eng J Med 2008359 2195-2207
97
JUPITER - Primary Endpoint Components
Placebo Rosuvastatin HR 95 CI P
value n8901 n8901 n (rate) n (rate)
Primary Endpoint 251 (1.36)
142 (0.77) 0.56 0.46-0.69 lt0.001 (Time to
first occurrence of CV death, MI, stroke,
unstable angina, arterial revascularisation) Non-
fatal MI 62 (0.33)
22 (0.12) 0.35 0.22-0.58 lt0.001 Fatal or
non-fatal MI 68 (0.37) 31
(0.17) 0.46 0.30-0.70 0.0002 Non-fatal stroke
58 (0.31) 30
(0.16) 0.52 0.33-0.80 0.003 Fatal or non-fatal
stroke 64 (0.34) 33
(0.18) 0.52 0.34-0.79 0.002 Arterial
Revascularization 131 (0.71) 71
(0.38) 0.54 0.41-0.72 lt0.0001 Unstable angina
27 (0.14) 16
(0.09) 0.59 0.32-1.10 0.09 CV death, stroke, MI
157 (0.85) 83
(0.45) 0.53 0.40-0.69 lt0.001 Revascularization
or unstable angina 143 (0.77)
76 (0.41) 0.53 0.40-0.70 lt0.001
Rates are per 100 person years
Hospitalisation due to unstable angina Actual
p-value was lt 0.00001
HRHazard Ratio CI Confidence Interval
Ridker P et al. N Eng J Med 2008359 2195-2207
98
JUPITER - Total Mortality Death from any cause
Hazard Ratio 0.80 (95 CI 0.67-0.97) p0.02
Placebo
0.06
Rosuvastatin 20mg
0.04
Cumulative Incidence
0.02
0.00
0
1
2
3
4
5
Years
Number at risk Rosuvastatin 8901 8787
4312 1602 676
227 Placebo 8901
8775 4319 1614
681 246
Ridker P et al. N Eng J Med 2008359 2195-2207
99
JUPITER Effects on LDL-C, HDL-C, TG and hsCRP
at 12 monthsPercentage change between
rosuvastatin and placebo
10
LDL-C
HDL-C
TG
hsCRP
4
0
plt0.001
-10
17
-20
Percentage change from baseline ()
plt0.001
-30
37
-40
plt0.001
50
-50
plt0.001
-60
P-value at study completion (48 months) 0.34
Ridker P et al. N Eng J Med 2008359 2195-2207
100
JUPITERTolerability and safety data
Placebo Rosuvastatin P value
n8901 n8901
Adverse Events, () Any serious adverse
event 15.5 15.2 0.60 Muscle weakness,
stiffness, pain 15.4 16.0 0.34 Myopathy 0.1
0.1 0.82 Rhabdomyolysis
0.0
lt0.1 ---- Newly diagnosed cancer 3.5 3.4 0.
51 Death from cancer 0.7 0.4 0.02 Gastrointest
inal disorders 19.2 19.7 0.43 Renal
disorders 5.4 6.0 0.08 Bleeding 3.1 2.9 0.
45 Hepatic disorders 2.1 2.4 0.13 Other
events, () Newly diagnosed diabetes 2.4 3.0
0.01 Haemorrhagic stroke
0.1 0.1 0.44
Occurred after trial completion physician
-reported
Ridker P et al. N Eng J Med 2008359 2195-2207
101
JUPITERLaboratory Safety Data
Placebo Rosuvastatin P
value n8901 n8901
Laboratory Values, N () Serum creatinine
10 (0.10)
16 (0.20) 0.24 ALT gt 3 x ULN
17 (0.20) 23
(0.30) 0.34 Glycosuria
32 (0.40) 36
(0.50) 0.64 Laboratory Values, median values
(IQR) GFR, (mL/min/1.73m2)
66.6 (58.8-76.2) 66.8
(59.1-76.5) 0.02 HbA1c
5.8 (5.6-6.1) 5.9
(5.7-6.1) 0.001 Fasting plasma glucose
(mmol/L) 5.4 (5.0-5.9) 5.4
(5.1-5.9) 0.12
gt100 increase from baseline on consecutive
visits gttrace at 12 months at 12 months,
at 24 months
GFR Glomerular filtration rate, HbA1c
Haemoglobin A1c IQR interquartile range
Ridker P et al. N Eng J Med 2008359 2195-2207
102
JUPITER summary and perspectives

• The JUPITER study included patients with low to
  normal LDL-C who were at increased CV risk as
  identified by elevated CRP levels and who did not
  require statin treatment based on current
  treatment guidelines
• A 44 reduction in the primary endpoint of major
  cardiovascular events (composite of CV death,
  MI, stroke, unstable angina, arterial
  revascularisation) was observed in patients who
  received rosuvastatin 20 mg compared with placebo
  (plt 0.00001)
• A 20 reduction in total mortality was observed
  in patients who received rosuvastatin 20 mg
  compared with placebo (p0.02), a unique finding
  for statins in a population without established
  CHD
• In JUPITER, long-term treatment with rosuvastatin
  20 mg was well tolerated in nearly 9000 study
  participants
• There was no difference between treatment groups
  for muscle weakness, cancer, haematological
  disorders, gastrointestinal, hepatic or renal
  systems
• The results from JUPITER highlight the importance
  of highly effective statin treatment for these
  patients with an increased risk of CV disease

Ridker P et al. N Eng J Med 2008359 2195-2207
103
GUIDELINESWHATS NEW AND WHATS NOT

• WWW.DIABETES.CA/FOR-PROFESSIONALS/2008-CPG
• WWW.HYPERTENSION.CA/CHEP
• WWW.LIPIDNURSE.CA
• WWW.CHRC.NET