APEKS:SIC V

Mid claviculer

Hypertension Heart Disease

Ddrdr. Murthado Sani SpJP(K)FIHA

Prevalence of hypertension

The World Health Organization (WHO)

estimates that 20% of the worlds
current adult population has
hypertension

Awareness, Treatment and Control of

High Blood Pressure in Canada
13%

21%

43%
22%

Patients unaware of their high blood pressure

Aware but not treated and not controlled
Treated but not controlled
Treated and controlled

43%
22%
21%
13%

Joffres et al. Am J Hypertens 2001; 14(11):1099-1105

Trends in the awareness, treatment

and control of hypertension in the
U.S.
NHANES II
1976-80

NHANES
III
(Phase I)
1988-91

73.0%

NHANES
III
(Phase II)
1991-94

Awareness

51.0%

68.4%

Treated

31.0%

55.0%

53.6%

Controlled

10.0%

29.0%

27.6%

Controlled BP = SBP <140 mmHg and DBP <90 mmHg

Adapted from Burt et al. 1995

Causes of Resistant Hypertension

Efficacy of
medications
Patient compliance:

Side effects (-)

Convenience
Lack of symptoms
Patient education
Cost

Failure to treat to
target
MD Reluctance
Accurate blood pressure
measurements

Secondary Causes

Sleep apnea
Renal vascular HTN
Endocrine causes
Chronic renal failure
Rx Drugs (NSAIDS, steroids)
White-coat HTN

Diseases Attributable to Hypertension

Coronary heart disease

Stroke
Heart failure
Cerebral hemorrhage

Myocardial infarction
Left ventricular
hypertrophy

Hypertension

Chronic kidney failure

Hypertensive
encephalopathy

Aortic aneurysm
Retinopathy
Peripheral vascular disease

Adapted from: Dustan et al. Arch Intern Med 1996; 156:1926-1935

All
Vascular

Hypertension Optimal Treatment (HOT) study

Intensive BP-lowering decreases cardiovascular risk in patients with
hypertension, especially among those with diabetes
Major CV
events per
1000 patient
years

30

All patients (n=18 790)

Diabetics (n=1501)

24.4

25
20

18.6

15
11.9

10

9.9

10.0

9.3

5
0
90 mmHg

85 mmHg

80 mmHg

Target DBP group

Lancet 1998;351:17551762

UKPDS: relative risk reduction with tight

versus less tight blood pressure control
Tight BP control decreases morbidity and mortality in patients with diabetes
Any diabetes- Diabetes-related
deaths
related endpoint

Stroke

Microvascular
disease

Deterioration in
visual acuity

24% P<0.005
32% P<0.05
37% P<0.01
Tight control (n=758)
Less tight control (n=390)

44% P<0.05

47% P<0.005
BMJ 1998;317:703713

BP targets

BP targets in guidelines are becoming

more stringent

Coexistent cardiovascular risk factor

profile is important

Strngt : ktat,kras

Initial Assessment
Target organ damage
Overall cardiovascular risk
Rule out secondary and often curable
causes

Components of Risk Stratification

Target Organ Damage/Clinical Cardiovascular Disease

Target end-organs should be assessed

by history and physical examination
Brain
Heart

Eyes

Kidneys

Arteries

Adapted from: JNC VI. Arch Intern Med 1997;157: 2413-46

Components of Risk Stratification

Major Cardiovascular Risk Factors

Hypertension
Age

> 45 years Male

> 55 years Female (Postmenopausal)

Smoking

Dyslipidemia
Diabetes
Family history

CAD <65 Female

CAD <55 Male

Obesity
Adapted from: JNC VI. Arch Intern Med 1997;157: 2413-46

Stratification of risk to quantity

prognosis
Blood pressure (mm Hg)
Other risk factor and
disease history

Normal
SBP 120129
DBP 80-84

High
normal
SBP 130139
DBP 85-89

Grade 1
SBP140159
DBP 9099

Grade 2
SBP 160179
DBP 100109

Grade 3
SBP >
180
DBP >
110

No other risk factors

Average
risk

Average
risk

Low
added
risk

Moderate
added risk

High
added
risk

1 2 risk factors

Low added
risk

Low added
risk

Moderate
added
risk

Moderate
added risk

Very high
added
risk

3 or more risk factors Moderate

or TOD or DM
added risk

High
added risk

High
added
risk

High
added risk

Very high
added
risk

ACC

Very high
added risk

Very high
added
risk

Very high
added rsik

Very
added
risk

High
added risk

2003 ESH-ESC

14

The ideal antihypertensive agent

Effectively reduces BP

Maintains BP control over 24 h with

once-a-day dosing

Effective in all hypertensive patients

No adverse effects

No negative metabolic side effects

Affordable

 Persistent use of monotherapy

Obsession with first line therapy
Poor recognition of the importance and efficacy
of combination therapy
Lack of advice on most appropriate drugs to
use in combination

BP monotherapy:BP fall <10%

Statin therapy:
Cholesterol fall 30-40%

Clinical Practice:
Most people with hypertension are treated with monotherapy

Clinical Evidence:
Most people in clinical trials are treated with combination
therapy

HOT(Hyp.Optimal.Treatment): percentage of
patients requiring combination therapy to
achieve target DBP
Target DBP group
90 mmHg

85 mmHg

26.1%

31.7%

37.1%
62.9%

80 mmHg

68.3%

73.9%

Combination therapy
Monotherapy

The lower the target DBP, the greater the need for combination therapy
HOT:Hypertesion Optimal Treatment

Advantages of combination therapy

Additive antihypertensive efficacy (due to
complementary mechanisms of action)
Higher patient response rates
Simple titration and dosing schedules
Maintained or improved tolerability
Improved patient compliance
Cost effective

Drug Action
- vasodilatation

RAS Activation
SNS Activation
-Vasoconstriction
- Sodium retention
RAS = renin-angiotensin system
SNS = sympathetic nervous system

Thiazide
Natriuretic
Lowers Blood
Pressure

Activates
Renin Angiotensin
System

Reduces antihypertensive effect

24

Reduce Adverse Effects of Drug Therapy:

ACE inhibition or
Angiotensin Receptor Blockers
Retain potassium(K)

Thiazide
Diuretics
Excrete Potassium

Combination
Prevents hypokalaemia of thiazide therapy
Limits hyperkalaemia of RAS(renin angt sys) blockade

25

26

27

28

WHAT IS THE IDEAL WAY OF CONTROLLING BP?

The new therapeutic window in hypertension
IDEAL treatment
100

100

80

80

60

60

Traditional

40

40

20

20

0
Dose

Efficacy (%)
Freedom from
side effects (%)

29
Man Int Veld AJ. J Hypert, 1997

30

31

Initial Drug Therapy

BP Classification
Normal
<120/80 mm Hg

Lifestyle
Modification

Without Compelling
Indication

With Compelling
Indication

Encourage

Prehypertension
120-139/80-89 mm Hg

Yes

No drug indicated

Stage 1 hypertension
140-159/90-99 mm Hg

Yes

Thiazide-type diuretics
for most; may consider
ACE-I, ARB, BB, CCB, or
combination

Stage 2 hypertension
160/100 mm Hg

Yes

2-drug combination for most

(usually thiazide-type diuretic
and ACE-I, ARB, BB, or
CCB)

Drug(s) for the compelling

indications
Drug(s) for the compelling
indications; other
antihypertensive drugs
(diuretics, ACE-I, ARB, BB,
CCB) as needed

Drug(s) for the compelling

indications; other
antihypertensive drugs
(diuretics, ACE-I, ARB,
BB, CCB) as needed
ACE-I = angiotensin-converting enzyme inhibitor; ARB = angiotensin-receptor blocker;
32
BB = beta blocker; CCB, = calcium channel blocker.
Chobanian AV et al. JAMA. 2003;289:2560-2572.

 BP target of <140/90 mm Hg for patients with uncomplicated

hypertension without compelling indications
BP target of <130/80 mm Hg for patients with diabetes

Combinations of 2 or more drugs are usually needed to

achieve target BP goal
BP target of <130/80 mm Hg for patients with chronic renal
disease*

Combinations of 3 or more drugs are often needed to

reach target BP goal
*Chronic kidney disease = GFR <60 mL/min per 1.73 m 2 or presence of albuminuria
(>300 mg/d or 200 mg/g creatinine).
Chobanian AV et al. JAMA. 2003;289:2560-2572.
American Diabetes Association. Diabetes Care. 2003;26(Suppl 1):S33-S50.
Guidelines Committee. J Hypertens. 2003;21:1011-1053.

33

 Most patients with hypertension will require 2 or

more antihypertensive drugs to achieve BP goals
According to baseline BP and presence or absence
of complications, therapy can be initiated either
with a low dose of a single agent or with a low-dose
combination of 2 agents
When BP is >20/10 mm Hg above goal,
consideration should be given to initiating 2 drugs,
either as separate prescriptions or in fixed-dose
combinations, one of which should be a thiazidetype diuretic
Chobanian AV et al. JAMA. 2003;289:2560-2572.
Guidelines Committee. J Hypertens. 2003;21:1011-1053.

34

Easy as ABCD
A = ACE-Inhibitor or Angiotensin Receptor Blocker
B = - Blocker
C = Calcium Channel Blocker
D = Diuretic (thiazide)
Adapted from : Better blood pressure control: how to combine drugs
Journal of Human Hypertension (2003) 17, 81-86 www.bhsoc.org

35

A or B

C or D

Inhibit the
Renin-Angiotensin
System

Do not inhibit the

Renin-Angiotensin
System

More Effective
In Younger

More Effective
In Older

Adapted from : Better blood pressure control: how to combine drugs

Journal of Human Hypertension (2003) 17, 81-86 www.bhsoc.org

36

1.

Younger
Or Diabetes
( 55yrs)

Older
(55yrs)
or Black

A or B

C or D

2.

A or (B) + C or D

3.

A or (B) + C + D

4.

A or (B) + C + D + other
Adapted from : Better blood pressure control: how to combine drugs
Journal of Human Hypertension (2003) 17, 81-86 www.bhsoc.org

38

Recommended Combinations
1. ACE inhibitors / AIIRA
2. ACE inhibitors / AIIRA
3. ACE inhibitors / AIIRA
4. Beta-Blockers
5. Beta-Blockers

Diuretics
Calcium antagonists
Beta-blockers
(Special condition)
Diuretics
Calcium Antagonists
39

SUMMARY
COMBINATION THERAPY IN HTN
MANAGEMENT IS LOGIC AND EVIDENCE
BASED
MAXIMIZE EFFECT, MINIMIZE SIDE
EFFECT
COMBINATION THERAPY IN HTN
INCREASE COMPLIANCE

THE END