Hypertension: Which Drug? Psirropoulos Dimitrios Z, MD, PhD

1
Hypertension Which Drug?

• Psirropoulos Dimitrios Z, MD, PhD
• Head Director, Cardiology Department CCU
• G. Gennimatas General Hospital
• Thessaloniki, Greece
• President of Society of Studying Cardiovascular
  Diseases, SOS-CVD

The First International Spring MeetingEdirne,
Turkey, 29th - 31st May 2009
2
What do we usually mean when speaking in general
for hypertension?

• Hypertension is sustained elevation of resting
  systolic BP ( 140 mm Hg), diastolic BP ( 90 mm
  Hg), or both.
• Hypertension with no known cause (primary,
  formerly, essential hypertension) is most common.
  
• Hypertension with an identified cause (secondary
  hypertension) is usually due to a renal disorder.
  
• Usually, no symptoms develop unless hypertension
  is severe or long-standing.
• Diagnosis is by sphygmomanometry.
• Tests may be done to determine cause, assess
  damage, and identify other cardiovascular risk
  factors.
• Treatment involves lifestyle changes and drugs,
  including mostly diuretics, ß - blockers, ACE
  inhibitors, angiotensin II receptor blockers, and
  Ca channel blockers.

3
Hypertension increases. with the age!
4

• What three factors contribute to blood pressure?

5
o
6
i
7
How would we define hypertension?
8
Definitions and Classification of BP Levels
(mmHg)
European Society of Hypertension, European
Society of Cardiology
Journal of Hypertension 2007251105-1187
9
Blood Pressure Classification
Seventh Joint USA National Committee on
Prevention, Detection, Evaluation, and Treatment
of High Blood Pressure -JNC 7, JAMA, May 21,
2003, and USA Government Printing Office
publication.
10

• ARTERIAL HYPERTENSION
• Stratification of
• CardioVascular risk

11

• The JNC 7 guidelines were published in 2003, and
  a lot has changed since then.
• Two new guidelines have suggested
  recommendations substantially different form JNC
  7, one from the American Heart Association, and
  the other from the European Society of
  Hypertension.
• Also, the 2009 Canadian Hypertension Education
  Program Recommendations are already published.
• New US National Hypertension Guidelines (JNC 8)
  are scheduled for 2009

Treatment of Hypertension in the prevention and
management of ischemic heart disease. Rosendorff
et al, Circulation 2007 115 2761-2788.
12
Stratification of CV risk in four categories
(Blood pressure - mmHg)
European Society of Hypertension, European
Society of Cardiology
Journal of Hypertension 2007251105-1187
13
Benefits of Lowering BP
Average Percent Reduction Stroke incidence
3540 Myocardial infarction 2025
Heart failure 50
Seventh Joint USA National Committee on
Prevention, Detection, Evaluation, and Treatment
of High Blood Pressure - JNC 7, JAMA, May 21,
2003, and USA Government Printing Office
publication.
14
Benefits of Lowering BP

• stage 1 HTN and additional CVD risk factors,
  achieving
• a sustained 12 mmHg reduction in SBP over 10
  years will
• prevent 1 death for every 11 patients treated.
• Pre-hypertension signals the need for increased
  education to reduce BP in order to prevent
  hypertension.

Seventh Joint USA National Committee on
Prevention, Detection, Evaluation, and Treatment
of High Blood Pressure - JNC 7, JAMA, May 21,
2003, and USA Government Printing Office
publication.
15
BP Reductions as Little as 2 mm Hg Reduce the
Risk of CV Events by Up to 10

• Meta-analysis of 61 prospective, observational
  studies
• 1 million adults
• 12.7 million person-years

7 reduction in risk of ischemic heart disease
mortality
2 mm Hg decrease in mean SBP
10 reduction in risk of stroke mortality
Lewington S et al. Lancet 20023601903-1913.
16
Approaching Hypertension
17
Patient Evaluation

• Evaluation of patients with documented HTN has
  three objectives
• A. Assess lifestyle and identify other CV risk
  factors or concomitant disorders that affect
  prognosis and guides treatment.
• B. Reveal identifiable causes of high BP.
• C. Assess the presence or absence of target organ
  damage and CVD.

18
A. CVD Risk Factors

• Hypertension
• Cigarette smoking
• Obesity (BMI gt30 kg/m2)
• Physical inactivity
• Dyslipidemia
• Diabetes mellitus
• Microalbuminuria or estimated GFR lt60 ml/min
• Age (older than 55 for men, 65 for women)
• Family history of premature CVD
• (men under age 55 or women under age 65)

Components of the metabolic syndrome (ESH
2007).
19
B. Identifiable Causes of Hypertension

• Sleep apnea
• Drug-induced or related causes
• Chronic kidney disease
• Primary aldosteronism
• Renovascular disease
• Chronic steroid therapy and Cushings syndrome
• Pheochromocytoma
• Coarctation of the aorta
• Thyroid or parathyroid disease

20
C. Target Organ Damage - TOD

• Heart
• Left ventricular hypertrophy
• Angina or prior myocardial infarction
• Prior coronary revascularization
• Heart failure
• Brain
• Stroke or transient ischemic attack
• Chronic kidney disease
• Peripheral arterial disease
• Retinopathy

21
Treatment Overview

• 1. Goals of therapy
• 2. Lifestyle modification
• 3. Pharmacologic treatment
• Algorithm for treatment of hypertension
• 4. Classification and management of BP for adults
• 5. Follow-up and monitoring

Seventh Joint USA National Committee on
Prevention, Detection, Evaluation, and Treatment
of High Blood Pressure - JNC 7, JAMA, May 21,
2003, and USA Government Printing Office
publication.
22
Goals of therapy

• Reduce CVD and renal morbidity and mortality.
• Treat to BP lt140/90 mmHg or BP lt130/80 mmHg in
  patients with diabetes or chronic kidney disease.
  
• Achieve SBP goal especially in persons gt50 years
  of age.

23
Approaching Hypertension Pharmacologic treatment
24
Reference Card
25
Algorithm for Treatment of Hypertension - 2003
Lifestyle Modifications
Not at Goal Blood Pressure (lt140/90 mmHg)
(lt130/80 mmHg for those with diabetes or chronic
kidney disease)
Initial Drug Choices
Seventh Joint USA National Committee on
Prevention, Detection, Evaluation, and Treatment
of High Blood Pressure - JNC 7, JAMA, May 21,
2003, and USA Government Printing Office
publication.
26
-Initiation of antihypertensive treatment - 2007
ESH/ESC - Journal of Hypertension
2007251105-1187
27
Brown MJ, et al. Journal of Human Hypertension
(2003) 17, 8186
28
Comments

• The guidelines for hypertension indicate that
  cardiovascular risk reduction resulting from the
  use of five categories of antihypertensive drugs,
  diuretics, beta-blockers, converting enzyme
  inhibitors (a-MEA), competitors of the
  angiotensin (AT1) and Calcium antagonists is the
  result of reduction in blood pressure
• Unclear, however, is whether the nature of the
  drug can be used to further reduce risk.

29
Comments

• The guidelines of the American National Committee
  for Hypertension (JNC 7) recommend diuretics as
  the 1st line drug for the majority of patients.
• The drug administration is recommended for all
  persons with BP gt 140/90 mmHg and in patients
  with diabetes or chronic kidney disease when the
  BP is gt 130/80 mmHg.
• In case that blood pressure is higher than the
  target by 20/10 mmHg for systolic and diastolic
  pressure, respectively, then is suggested to
  initiate therapy with two drugs, one of which may
  be diuretic.

30
Comments

• According to the instructions of the British
  Hypertension Society (British Hypertension
  Society) the best initial option in people aged
• lt55 years are ACE-I or AT1
• and in those aged gt 55 years, calcium
  antagonists or thiazide diuretics.

31
Comments
In contrast, beta-blocking medicine is
recommended as 1st line in young people where is
contraindicated the administration of ACE-I and
AT1, in women who are planning to have children
or people with increased sympathetic activity.
In hypertensive pts receiving beta-blockade is
recommended change to another drug class only
when there is not sufficient BP management.
32
Comments

• The recently published guidelines of the American
  Heart Association recommend as their first choice
  the ACE-I, the AT1, the calcium antagonists and
  diuretics.
• The beta-blocking awarded only when there is an
  absolute indication, such as effort angina or
  after myocardial infarct.
• Also, elderly gt80 years as recommended
  antihypertensive treatment significantly reduced
  the risk for cerebro-vascular manifestations.

33
Comments
The guidelines of the World Health Organization
are identified with the earlier reference to the
objectives of the pressure and the 1st-line
drugs. But there is disagreement in the cases
of failure to regulate a drug in small doses,
which proposed a gradual increase in dose and
subsequent addition of another drug category.
34
Comments

• The European Society of Hypertension and the
  European Society of Cardiology concluded that all
  five categories of drugs are appropriate for the
  initiation of treatment.
• The beta-blocking, however, especially when
  combined with a thiazide diuretic, should not be
  administered to patients with metabolic syndrome
  or in individuals with increased risk of
  diabetes.

35
Comments

• As shown by the previous guidelines their main
  arguments concerns the use of beta-blockers as
  1st line drugs.
• So could be proposed that this class is
  recommended as initial therapy in hypertension a)
  only to persons aged lt55 years and only if is
  contraindicated the use of other categories of
  drugs and also b) in hypertensives aged gt 55
  years only when heart failure and history of
  myocardial infarction or angina coexist.
• Also, beta-blocking can be used as medicines on
  the 2nd or 3rd line for enhancing the effect of
  other antihypertensive classes.

36
First line anti-hypertensive drugs
37
Special Considerations

• A. Compelling Indications
• B. Other Special Situations
• B1. Minority populations
• B2. Obesity and the metabolic syndrome
• B3. Left ventricular hypertrophy
• B4. Peripheral arterial disease
• B5. Hypertension in older persons
• B6. Postural hypotension
• B7. Dementia
• B8. Hypertension in women
• B9. Hypertension in children and adolescents
• B10. Hypertension urgencies and emergencies

38
A. Compelling Indications for Individual Drug
Classes
39
A. Compelling Indications for Individual Drug
Classes
40
B1. Minority Populations

• In general, treatment similar for all demographic
  groups.
• Socioeconomic factors and lifestyle important
  barriers to BP control.
• Prevalence, severity of HTN increased in African
  Americans.
• African Americans demonstrate somewhat reduced BP
  responses to monotherapy with BBs, ACEIs, or ARBs
  compared to diuretics or CCBs.
• These differences are usually eliminated by
  adding adequate doses of a diuretic.

41
B3. Left Ventricular Hypertrophy

• LVH is an independent risk factor that increases
  the risk of CVD.
• Regression of LVH occurs with aggressive BP
  management weight loss, sodium restriction, and
  treatment with all classes of drugs except the
  direct vasodilators, hydralazine and minoxidil.

42
B4. Peripheral Arterial Disease(PAD)

• PAD is equivalent in risk to ischemic heart
  disease.
• Any class of drugs can be used in most PAD
  patients.
• Other risk factors should be managed
  aggressively.
• Aspirin should be used.

43
B5. Hypertension in OlderPersons

• More than two-thirds of people over 65 have HTN.
• This population has the lowest rates of BP
  control.
• Treatment, including those who with isolated
  systolic HTN, should follow same principles
  outlined for general care of HTN.
• Lower initial drug doses may be indicated to
  avoid symptoms standard doses and multiple drugs
  will be needed to reach BP targets.

44
Results of Tight Blood Pressure Control Compared
with Less-Tight BP Control in the UKPDS Study
Risk Reduction ()
Any diabetes related end- point
Diabetes related death
Stroke
Micro vascular endpoints
Retinopathy progression
Deterior- ation of vision
Heart failure
BMJ 1998317703-713
45
Benefits of Lowering BP by
Average Percent Reduction Stroke incidence
3540 Myocardial infarction 2025
Heart failure 50
46
The Difficulty in Reducing SBP STOP-2
Conventional ACEI based Calcium antagonist based
SBP Goal
? BP(mm Hg)
DBP Goal
1
0
6
12
24
36
48
54
Months
Swedish Trial in Old Patients with Hypertension-2
(STOP-2), Hansson L, et al. Lancet.
19993541751-1756.
47
Diuretics or B-Blockers as Initial Therapy in 8
Randomized Controlled Hypertension Treatment
Trials in Older Persons
Risk Reduction ()
All reductions significant (p lt.05) except CHD
and death with B-blockers
Cutler JA, et al. In Laragh JH, Brenner BM, eds,
Hypertension 1995
48
B6. Postural Hypotension

• Decrease in standing SBP gt10 mmHg, when
  associated with dizziness/fainting, more frequent
  in older SBP patients with diabetes, taking
  diuretics, venodilators, and some psychotropic
  drugs.
• BP in these individuals should be monitored in
  the upright position.
• Avoid volume depletion and excessively rapid dose
  titration of drugs.

49
Isolated Systolic Hypertension
Definition gt140 lt90 mm
Hg Etiology Age related decrease in aortic
compliance (increase in
vascular stiffness)
Decrease in elastic tissue In rigid
aorta Increase in collagen deposition
Intimal thickening
Diastolic pressure remains constant or
decreases. In rigid aorta elastic recoil that
helps maintain DBP is decreased.
50

• Algorithm for Management of the Elderly -
• Primarily Systolic Hypertension
• 1) Lifestyle changes
• Low dose diuretic (12.5 mg HCTZ)
• CCB B-Blocker
  ACE or ARB
• 3) Stop, Look Listen before dosages
• Let the Baroreceptors reset
• 4) Rx until goal achieved

51
B8. Hypertension in Women

• Oral contraceptives may increase BP, and BP
  should be checked regularly. In contrast, HRT
  does not raise BP.
• Development of HTNconsider other forms of
  contraception.
• Pregnant women with HTN should be followed
  carefully. Methyldopa, BBs, and vasodilators,
  preferred for the safety of the fetus.
• ACEI and ARBs are contraindicated in pregnancy.

52
B9. Children and Adolescents

• HTN defined as BP95th percentile or greater,
  adjusted for age, height, and gender.
• Use lifestyle interventions first, then drug
  therapy for higher levels of BP or if
  insufficient response to lifestyle modifications.
• Drug choices similar in children and adults, but
  effective doses are often smaller.
• Uncomplicated HTN not a reason to restrict
  physical activity.

53
Additional Considerations in Antihypertensive
Drug Choices

• Potential favorable effects
• Thiazide-type diuretics useful in slowing
  demineralization in osteoporosis.
• BBs useful in the treatment of atrial
  tachyarrhythmias-fibrillation, migraine,
  thyrotoxicosis (short-term), essential tremor, or
  perioperative HTN.
• CCBs useful in Raynauds syndrome and certain
  arrhythmias.
• Alpha-blockers useful in prostatism.

54
Additional Considerations in Antihypertensive
Drug Choices

• Potential unfavorable effects
• Thiazide diuretics should be used cautiously in
  gout or a history of significant hyponatremia.
• BBs should be generally avoided in patients with
  asthma, reactive airways disease, or second- or
  third-degree heart block.
• ACEIs and ARBs are contraindicated in pregnant
  women or those likely to become pregnant.
• ACEIs should not be used in individuals with a
  history of angioedema.
• Aldosterone antagonists and potassium-sparing
  diuretics can cause hyperkalemia.

55

• Antihypertensive Treatment
• Preferred Drugs as Per New European Guidelines
  2007
• Subclinical organ damage Treatment
• LVH ACE inhibitors, calcium antagonists,
  angiotensin receptor blockers
• Asymptomatic atherosclerosis Calcium
  antagonists, ACE inhibitors
• Microalbuminuria ACE inhibitors, angiotensin
  receptor blockers
• Renal dysfunction ACE inhibitors, angiotensin
  receptor blockers
• Clinical event
• Previous stroke Any BP-lowering agent
• Previous MI Beta blockers, ACE inhibitors,
  angiotensin receptor blockers
• Angina pectoris Beta blockers, calcium
  antagonists
• Heart failure Diuretics, beta blocker, ACE
  inhibitors, angiotensin receptor blockers,
  antialdosterone agents
• Atrial fibrillation Recurrent Angiotensin
  receptor blockers, ACE inhibitors
  Permanent Beta blockers, nonhydropyridine
  calcium antagonists
• ESRD/proteinuria ACE inhibitors, angiotensin
  receptor blockers, loop diuretics
• PAD Calcium antagonists
• Condition
• ISH (elderly) Diuretics, calcium antagonists
• Metabolic syndrome ACE inhibitors, angiotensin
  receptor blockers, calcium antagonists

56
Population-Based Strategy
SBP Distributions
Before Intervention
After Intervention
Reduction in BP
Reduction in SBP mmHg 2 3 5
Reduction in Mortality
Stroke CHD Total 6 4 3 8 5 4 14 9 7
Whelton, P. K. et al. JAMA 20022881882-1888
57
Incidence of New Onset Diabetes with Various
Medications. How significant is it?
58
Risk of Hyperglycemia with Use of Antihypertensive
Drugs

Thiazide Central antiadrenergic agents
Peripheral antiadrenergic agents
ACE inhibitors
B-Blockers Calcium
channel blockers
Vasodilators gt1 Agent without
thiazide gt1 Agent with thiazide
0.5 1 1.5 2 2.5 3
Decreased Risk
Increased Risk
Gurwitz J H. Arch Intern Med 1993118273-278
Adjusted ORs and 95 CI
59
Effects of High-Dose Diuretic Therapy Compared
To Control or Placebo on Glucose Metabolism
Study Yrs Hyperglycemia or
Diabetes Oslo 5 No
data EWPHE MRC
3-4 Excess of 6 new cases/1000 pt
yrs HAPPY HDFP 5 1.6
(57/3,563) SHEP 1 No diff new onset
diabetes Rx/C

Moser, M. Cleve Clin J Med 19936027-37
60
Incidence of New Onset Diabetes in the 3-8 Year
Hypertension Treatment Trials

Years Absolute
Difference Trial Duration
New Onset Diabetes
I. ACE-I compared to conventional Rx ACE / D
/ B-BL CAPPP 6.1
-1.0 STOP-2 6
-0.2 ANBP-2
4
-2.1 ALLHAT
4.9 - 3.5 II.
CCB compared to conventional Rx CCB / D /B-BL
NORDIL 4.5 -
0.6 ALLHAT 4.9
- 1.8 INVEST 4.0
- 1.1 INSIGHT 3.5
- 1.6 STOP-2 6
- 0.1
Approximate overall difference ACEI vs D/B-BL
2.0 CCB vs D/B-B/L 1.5
61
Incidence of New Onset Diabetes in the 3-8 Year
Hypertension Treatment Trials
Years Absolute Difference
Trial Duration New Onset
Diabetes

• III. ARB vs other Rx ARB /
  Other Rx
• VALUE 4.2
  - 3.3
• LIFE 4.8
  - 2.0
• SCOPE 5
  - 1.0
• CHARM 3
  - 1.4
• IV. ACE-I vs CCB ACE / CCB
• ALLHAT 4.9
  -1.7

Approximate overall difference ARB vs D/B-BL
2.0 ACE/CCB 2.0
62
Prognostic Significance of New Diabetes in
Treated Hypertensive Subjects

• At entry and at 3 year follow-up non diabetic
  patients who developed diabetes had
• higher SBP and DBP
• more LVH
• higher glucose levels
• 42 vs 6 who developed NOD had IFG

Greater baseline risk more diabetes
more events
Verdeccia, Hypertens 200443963-968
(observational cohort study)
63
Many clinical trial results demonstrate that

• Fewer cases of new onset diabetes occur if an ACE
  or an ARB is included in therapy
• Diabetic patients, especially those with
  proteinuria, have a better outcome if an ACE or
  an ARB based regimen usually with a diuretic
  is given rather than a CCB

IDNT, RENAAL, LIFE, HOPE, CAPPP, AASK, VALUE,
ALLHAT
64
Conclusions Concern about the risk of
diabetes should not discourage physicians from
prescribing thiazide diuretics to nondiabetic
adults who have hypertension. The use of
B-blockers appears to increase the risk of
diabetes, but this adverse effect must be weighed
against the proven benefits of B-blockers in
reducing the risk of cardiovascular events.
Gress, et al. NEJM 2000342905-12
65
While data indicate that NOD is increased by
about 1 with diuretics compared to CCBs and
1-3.5 compared to ACEIs, long-term CV
outcomes are not affected.
66
Recommendations for a change in
treatment approaches should be made based on
consistent evidence from well controlled
clinical trials. At present data on new onset
diabetes do not satisfy these criteria.
67

• Monotherapy
• or combination treatment
• for hypertension

68
Monotherapy

• Antihypertensive monotherapy is effective in only
  about 40-60 of hypertensive patients,
  irrespective of the category of the agent that is
  used.
• Most of the responders are Stage I hypertensives.
  Therefore, there is frequently a need for the
  use of two medications with different mechanisms
  of action.
• Should therapy be started with two drugs or a
  combination?

69
The concept of combination therapy is not new.
Every major hypertension treatment trial has
been a study of multiple drug therapy. This was
necessary to achieve goal BP.
70
Multiple Drug Therapy in the Clinical Trials
SHEP - only 46 on diuretic alone LIFE
- gt 85 on multiple drugs UKPDS - 29 in
tight BP group on 3 or more drugs compared to 11
in less tight BP group -MDRD, ABCD, AASK, IDNT,
HOT - - More than 3 medications necessary to
attain goal BP
71
Causes of Resistant Hypertension

• Improper BP measurement
• Excess sodium intake
• Inadequate diuretic therapy
• Medication
• Inadequate doses
• Drug actions and interactions (e.g.,
  non-steroidal anti-inflammatory drugs - NSAIDs,
  illicit drugs, oral contraceptives,
  sympathomimetics)
• Over-the-counter (OTC) drugs and herbal
  supplements
• Excess alcohol intake
• Identifiable causes of HTN

72
Drug-related Causes of Resistance
Objective Medication Intolerance
5
6
9
Suboptimal
Drug-related
5
Medication
58
Regimen
1
94
Drug interactions
16
73
Combination versus Monotherapy
Risk Reduction ( 95CI )
Favors active
Favors placebo

• Stroke
• Combination 43
• Single Drug 5 (-19 to 23)
• Total Stroke 28

0.4
1.0
2.0
Hazard Ratio
Lancet 2001 358 1033-41 - PROGRESS Study
74
Lower Blood Pressure Goals
Lower Treatment Goals Reduces the Success of
Monotherapy
Hansson et al. Lancet 1998 3511755-1762
75
Baroreflex hypertension therapy Chronic
Treatment of Resistant Hypertension with an
Implantable Medical Device Interim 3 Year
Results of Two Studies of the Rheos Hypertension
System
1 Washington University School of
Medicine 2Academisch Ziekenhuis Maastricht
(AZM) 3 CVRx, Inc.
76
Majority of US Hypertensive Patients Not at
Systolic BP Goal of lt 140 mmHg
Hypertensive N 73.6 million
Aware (79) 57.9 million
Unaware (21) 15.7 million
Untreated (10) 7.1 million
Treated (69) 50.8 million
40.2 million (55) not at goal
Controlled (45) 33.4 million
Uncontrolled (24) 17.4 million
D Lloyd-Jones et al., Circulation, Heart Disease
and Stroke Statistics 2009 Update
6e87-e95 Based on Data from NHANES/NCHS 2005-2006
77
The CVRx Rheos System
Programming System
Baroreflex Activation Leads
Implantable Pulse Generator
78
Comprehensive Mechanism of Action
79
Ability to Personalize and Control the Therapy
80
Office BP Response to Rheos Therapy
Systolic (Baseline 183 mmHg)
Diastolic (Baseline 105 mmHg)
Heart Rate (Baseline 78 BPM)
-5
-7
-8
Mean change in mmHg or BPM
-15
-15
-21
-22
-25
-31
p value lt 0.001 p value lt 0.005 p value
0.15
81
Cardiac Structure and Function Improvements
Values mean SD p value lt0.05
Bisognano JD. Journal of Cardiac Failure
200814(No. 6S Suppl)S48.
82
Case ExampleLVMi and BP Reduction Following 3
Months of Rheos Therapy
Pre-Implant
3-Months of Therapy
LVMI 119.9 g/m2
LVMI 97.0 g/m2
Septal Wall Thickness 1.16 cm LV End-Diastolic
Diameter 5.16 cm BP 185/95 mmHg ATI 22.5
BMI 34.4 kg/m2
Septal Wall Thickness 0.90 cm LV End-Diastolic
Diameter 4.12 cm (SBP ? 30 mmHg, DBP ? 14
mmHg) ATI 22.5 BMI 33.9 kg/m2
83
Case ExampleLVMi and BP Reduction Following 3
Months of Rheos Therapy
Pre-Implant
3-Months of Therapy
84
Conclusions

• Baroreflex hypertension therapy demonstrates
  clinically meaningful and sustained reduction in
  blood pressure in subjects with drug resistant
  hypertension
• The Rheos therapy also has been shown to improve
  cardiac structure and function.

85
ESH 2003 Possible combinations between some
classes of anti-hypertensive drugs
ESH/ESC 2007

• The most rational combinations are represented
  as thick lines
• Journal of Hypertension 2007, 25 1105-1187

86
Finally,

• The great truth is what?
• Wide knowledge of hypertension treatment trials
• Respect to guidelines
• Experience

87

• Thank you

88
(No Transcript)
89
V. Choice of Pharmacological Treatment
Uncomplicated
Associated risk factors? or Target organ
damage/complications? or Concomitant
diseases/conditions?
2009 Canadian Hypertension Education Program
Recommendations
90
V. Choice of Pharmacological Treatment

• 1. Treatment of Systolic/Diastolic hypertension
  without other compelling indications
• 2. Treatment of Isolated Systolic hypertension
  without other compelling indications

2009 Canadian Hypertension Education Program
Recommendations
91
V. Summary Treatment of Systolic-Diastolic
Hypertension without Other Compelling Indications
TARGET lt140/90 mmHg
Lifestyle modification
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
Initial therapy
Dual Combination

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

Not indicated as first line therapy over 60 y
Triple or Quadruple Therapy
2009 Canadian Hypertension Education Program
Recommendations
92
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
2009 Canadian Hypertension Education Program
Recommendations
93
Choice of Pharmacological Treatment for
Hypertension

• Individualized treatment
• Compelling indications
• Ischemic Heart Disease
• Recent ST Segment Elevation-MI or non-ST Segment
  Elevation-MI
• Left Ventricular Systolic Dysfunction
• Cerebrovascular Disease
• Left Ventricular Hypertrophy
• Non Diabetic Chronic Kidney Disease
• Renovascular Disease
• Smoking
• Diabetes Mellitus
• With Diabetic Nephropathy
• Without Diabetic Nephropathy
• Global Vascular Protection for Hypertensive
  Patients
• Statins if 3 or more additional cardiovascular
  risks
• Aspirin once blood pressure is controlled

2009 Canadian Hypertension Education Program
Recommendations
94
VI. Treatment of Hypertension in Patients with
Ischemic Heart Disease

• Caution should be exercised when combining a
  non DHP-CCB and a beta-blocker
• If abnormal systolic left ventricular
  function avoid non DHP-CCB (Verapamil or
  Diltiazem)
• Combinations of an ACEI with an ARB are not
  recommended in the absence of heart failure

Those at low risk with well controlled risk
factors may not benefit from ACEI therapy
2009 Canadian Hypertension Education Program
Recommendations
95
VI. Treatment of Hypertension in Patients with
Recent ST Segment Elevation-MI or non-ST Segment
Elevation-MI
Beta-blocker and ACEI or ARB (if ACEI not
tolerated)
Recent myocardial infarction
If beta-blocker contraindicated or not effective
Long-acting Dihydropyridine CCB (e.g.
Amlodipine)
YES
Heart Failure ?
NO
Long-acting CCB
Avoid non dihydropyridine CCBs (diltiazem,
verapamil)
2009 Canadian Hypertension Education Program
Recommendations
96
VII. Treatment of Hypertension with Left
Ventricular Systolic Dysfunction
ACEI and Beta blocker if ACEI intolerant
ARB Titrate doses of ACEI or ARB to those used in
clinical trials
Systolic cardiac dysfunction

• If additional therapy is needed
• Diuretic (Thiazide for hypertension Loop for
  volume control)
• for CHF class III-IV or post MI Aldosterone
  Antagonist

If ACEI and ARB are contraindicated Hydralazine
and Isosorbide dinitrate in combination
If additional antihypertensive therapy is
needed ACEI / ARB Combination
Long-acting DHP-CCB (Amlodipine)
Beta-blockers used in clinical trials were
bisoprolol, carvedilol and metoprolol.
2009 Canadian Hypertension Education Program
Recommendations
97
VIII. Treatment of Hypertensionfor Patients
with Cerebrovascular Disease
Combinations of an ACEI with an ARB are not
recommended
2009 Canadian Hypertension Education Program
Recommendations
98
IX. Treatment of Hypertension in Patients with
Left Ventricular Hypertrophy
Hypertensive patients with left ventricular
hypertrophy should be treated with
antihypertensive therapy to lower the rate of
subsequent cardiovascular events.

• ACEI
• ARB,
• CCB
• Thiazide Diuretic
• - BB (if age below 60)

2009 Canadian Hypertension Education Program
Recommendations
99
X. Treatment of Hypertension in Patients with Non
Diabetic Chronic Kidney Disease
albumincreatinine ratio ACR gt 30 mg/mmol or
urinary protein gt 500 mg/24hr
Monitor serum potassium and creatinine carefully
in patients with CKD prescribed an ACEI or
ARB Combinations of a ACEI and a ARB are
specifically not recommended in the absence of
proteinuria
2009 Canadian Hypertension Education Program
Recommendations
100
XI. Treatment of Hypertension in Patients with
Renovascular Disease
2009 Canadian Hypertension Education Program
Recommendations
101
XII. Treatment of Hypertension in association
with Diabetes Mellitus
2009 Canadian Hypertension Education Program
Recommendations
102
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
2009 Canadian Hypertension Education Program
Recommendations
103
XIII. Treatment of Hypertension for Patients
Who Use Tobacco
2009 Canadian Hypertension Education Program
Recommendations
104
Last full review/revision July 2007 by George L.
Bakris, MD
105
Last full review/revision July 2007 by George L.
Bakris, MD
106

• American Heart Association
• -The new recommendation here is that high risk
  individuals, defined as those patients with known
  coronary artery disease, or with CAD risk
  equivalents (carotid artery disease, peripheral
  arterial disease, or abdominal aortic aneurysm,or
  a 10 year Framingham risk score of more than 10)
  should have their blood pressure lowered to less
  than 130/80 mmHg.
• While observational trials certainly suggest that
  risk is lower at very low levels of BP, the
  evidence from interventional trials that support
  this argument is thin.
• -The main support comes from the CAMELOT trial,
  which was performed in patients with documented
  CAD, in which the primary outcome was change in
  the volume of atheromatous plaque measured by
  intravascular ultrasound.

Treatment of Hypertension in the prevention and
management of ischemic heart disease. Rosendorff
et al, Circulation 2007 115 2761-2788.
107

• European Society of Hypertension
• 2007 Guidelines for the Management
• of Arterial Hypertension.
• The trend towards a lower target blood pressure
  is also apparent here, where it is suggested
  among others that Antihypertensive treatment
  should be more aggressive in diabetics, in whom a
  target blood pressure of lt130/80 mmHg appears a
  reasonable one. Similar targets should be adopted
  in individual with cerebrovascular disease and
  can at least be considered in patients with
  coronary disease.
• -The basis for the recommendation about stroke
  patients was the PROGRESS study, which showed
  that lowering the blood pressure in already
  normotensive subjects reduced the likelihood of
  recurrent strokes.

Journal of Hypertension 2007 25 1105-1187
108
British Hypertension Society

• -Another topical issue is the use of beta
  blockers, which the British Hypertension Society
  have stated are no longer preferred as routine
  initial therapy for hypertension (see their web
  page http//www.bhsoc.org/ for more details).
• -The European Guidelines say Thus beta-blockers
  may still be considered an option for initial and
  subsequent antihypertensive treatment strategies.
  Because they favor an increase in weight, have
  adverse effects on lipid metabolism and increase
  (compared with other drugs) the incidence of new
  onset diabetes, they should not be preferred,
  however, in hypertensives with multiple metabolic
  risk factors including the metabolic syndrome

http//www.bhsoc.org