The Role of Ca-blockers in

The Management of Older

People with Hypertension
 Definition of Hypertension
• ISH/WHO has agreed to adopt in principle the
definition and classification provided in JNC-VI.
New definition defines the lower limits of
hypertension as 140 mmHg SBP and 90 mmHg
DBP

• Hypertension is therefore defined as a SBP of 140

mmHg or greater and/or a DBP of 90 mmHg or
greater in a subject who are not taking
antihypertensive medication.

WHO/ISH Guidelines
2
Chalmers J., et al. J. Hypertension. 1999 ; 17
Relative risk for cardiovascular disease of
elevated systolic and diastolic blood
pressure

3
Systolic BP
2

1
Diastolic BP
0
<110 110-119 120-129 130-135 135-139 140-149 150-159 >160

<70 70-75 76-80 81-85 86-90 91-95 96-100 >100 4

 Hypertension
And End-Organ Damage

Left ventricular Heart Failure Coronary heart

hypertrophy disease

Persistently elevated
blood pressure

PVD Stroke
End-stage renal disease

5
Treatment of Hypertension Background

• Hypertension is the major risk factor for coronary heart

disease and congestive heart failure
• Hypertension is second only to diabetes as the cause of
renal failure
• In a recent meta analysis, treating hypertension reduced
the incidence of stroke by 38% and coronary heart disease
by 16%
• In a US survey, only 21% of hypertensive patients had their
blood pressure controlled at <140/90 mmHg
 Goal of Hypertension Therapy

To achieve the maximum reduction in the

total risk of cardiovascular / target vital organ
morbidity and mortality

Target:
BP: SBP < 130 – 140 mm Hg
DBP < 90 mm Hg
JNC. VI, 1997 & WHO – ISH, 1999
Algorithm for the Treatment of Hypertension
Begin or Continue Lifestyle Modifications

Not at Goal Blood Pressure (<140/ 90 mmHg)

Lower goals for patients with diabetes or renal disease

Initial Drug Choices

Diuretics , Beta-Blockers, Calcium Channel Blockers ( CCBs ), ACE Inhibitor & AIIRA

Not at Goal Blood Pressure

No response or troublesome side effects Inadequate response but well tolerated

Substitute another drug from Add a second agent from a different

a different class class ( diuretic if not already used )

Not at Goal Blood Pressure

Continue adding agents from other classes.

Consider referral to a hypertension specialist
 Results of therapy
Effect of antihypertensive drug treatment
on cardiovascular events
% reduction of events

-10
-16
-20 -21
-30
-35
-40 -38

-50 -52
-60
CHF Strokes LVH CVD death CHD
fatal/non events

Combined results of 17 randomized placebo controlled trial (48000 pts)

9
with diuretics or betablocker. Moser;AJCC;1996;27:1214-1218
 Guidelines:

WHO-ISH:

Target blood pressure:

• young and middle age <130/85mmHg

• elderly <140/90mmHg

10
 Recommendations for antihypertensive
treatment in elderly patients
3 consecutive measurements
Threshold BP
SBP DBP Target BP
mm Hg mm Hg mm Hg

WHO/ISH 1993 160 95 <140/90

Working group on 140 90 <140/90 or

hypertension in 20 mm Hg  in SBP
the elderly (USA)

Sweden 180 100 <160/90

11
 Concomitant disorders are common in
hypertensive at age 70
CHD
No hypertension
Angina (n=2338)
pectoris

Myocardial Hypertension
infarction (n=755)

Stroke

Diabetes

Claudication
Obstructive
Lung disease
%

0 5 10 15 20 25 30 35 40 45
Landahl 1996
12
Venous function is reduced with age

Muscle strength Baroreceptor function

Venous tone Plasma volume

Valvular function

Hydrostatic capillary Postural hypotension

pressure

Peripheral edemas

13
Principles of management of hypertension
in the elderly

Therapeutics strategies: ISH = diastolic hypertension

Start with lifestyle modifications

Avoid drugs that may worsen co-morbid condition or

induce orthostatic hypotension or cognitive
dysfunction

Low starting dose - usually half recommended in

younger patients

14
 Drug therapy in the elderly

• Goal of therapy <140/90 mmHg

• Choice of anti-hypertensive agent depend
on the presence of concomitant
conditions
• First line: low dose diuretics
• Beta blocker is not the drug of choice,
except in angina or post AMI
• ACEI and calcium blocker if diuretics and
beta blocker contraindicated ( asthma,
diabetes )
15
 Ten trials which used first line drug diuretics or
betablocker, involving 16164 elderly patients

Diuretics B-blocker
• Cerebrovascular events 0.61 0.75
• Fatal strokes 0.67
• Coronary heart disease 0.74 1.01
• Cardiovascular death 0.75 0.98
• All causes mortality 0.86 1.05

Messerli: Jama1998:279:1903-1907
16
Messerli FH: JAMA 1998;279:1903-1907

Conclusion: In contrast to diuretics, which

remain the standard first line therapy,
beta-blocker until proven otherwise,
should no longer be considered
appropriate first line therapy of
uncomplicated hypertension in the elderly
hypertensive patients
 Drug therapy in the elderly:

• Diabetes Mellitus, congestive HF,

ACEI
• Angina Pectoris, post MI
Beta-blocker
• Isolated systolic hypertension
Diuretic/Ca antagonist

18
 Ideal Antihypertensive Agent

EFFECTIVE - for systolic & diastolic hypertension

EASY TO USE – once a day

SAFE – free of brain, heart & kidney side effects

AFFORDABLE – economical daily cost

Int’l Forum on Angiotensin Receptor Antagonist, Monte Carlo, 19999

 Calcium Channel Blockers (CCBs)

 Dihydropyridine ( DHP )
Nifedipine, Amlodipine, Felodipine
 Non-Dihydropyridine ( NDHP )
Diltiazem, Verapamil

Opie, Drugs for the Heart, 2001

 Calcium Channel Blockers (CCBs)

Advantages
• Highly effective in reducing BP in the elderly
• Favorable or neutral effects on concomitant disease
• Symptomatic relief of angina pectoris
• No metabolic side-effects

Disadvantages
• Tachycardia
• AV block
• Constipation
• Ankle edema
 Through / Peak (T/P) Ratio

• Guidelines for the Clinical Evaluation of

Antihypertensive Drugs 1988 (Cardio-
renal Division of FDA) :
• The drug effect at trough (measured as the
difference from the placebo effect) should be no
less than 1/2 to 2/3 of the peak effect,
depending on the magnitude of the effect.

22
Through / Peak Ratio of HERBESSER® CD 72 %
Diltiazem Hydrochloride Sustained Released (HERBESSER® CD) on Essential Hypertension Evaluated by
24-hour Ambulatory Blood Pressure Monitoring (ABPM)

Oiwa J et al., Pharma Medica 18 (5) : 139-147 : 2000

Hypertension Efficacy of HERBESSER® CD
Clinical Effect of Diltiazem Hydrochloride Sustained Released Preparation (HERBESSER® CD) on Essential Hypertension
– A Double Blind Study with Diltiazem Hydrochloride Current Product

** : p<0.01 (vs baseline) Mean + S.D. n = 37 Subject : Essential hypertension ( mild to moderate ) 53 cases
Method : HERBESSER® CD 100-200 mg once a day for 12 weeks

K. Arakawa et al, J. Clinical Therapeutics & Medicines 1989 ; 5: 171

Cardio Protective Effect of HERBESSER CD
( DRS Study )

25
Cardio Protective Effect of HERBESSER® CD
( INTERCEPT )
INTERCEPT : Diltiazem reduced cardiac death, non-fatal re-infarction or refractory
ischemia, and the need for PTCA / CABG in acute myocardial infarction (AMI).
1.20
Cardiac death Cardiac death
Cardiac death Non-fatal Non-fatal
+ Non-fatal + Non-fatal Non-fatal
+ Non-fatal reinfarction + reinfarction +
1.10 reinfarction + reinfarction +
reinfarction + Refractory All recurrent
reinfarction + PTCA/CABG
Refractory All recurrent PTCA/CABG
PTCA/CABG ischemia ischemia
ischemia ischemia
1.00

0.90

0.80

0.70

0.60
21% 19% 29% 24% 20% 33% 39%
P= 0.07 P= 0.07 P= 0.05 P= 0.05 P= 0.05 P= 0.03 P= 0.03
0.50
William E. Boden, et al;, Lancet, 2000, 355: 1751-1756
Cerebral Protective Effect of HERBESSER® CD
( NORDIL Study )
NORDIL STUDY : showed Diltiazem group had a 20% lower rate of all
stroke than Diuretics and -Blockers

The Lancet, Vol 356, July 29, 2000

 Summary:
• Prevalence of hypertension in the elderly is
quite high ( 60%-71%).
• There is convincing evident that treatment of
hypertension in the elderly is beneficial, it will
reduce cardiovascular morbidity and mortality.
• Blood pressure reduction is more important
than specific drug.
• Low dose diuretic is the first line drug
• Selection of the drugs depend on the comorbid
disease.

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