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Focus on Bisoprolol
ISFANUDDIN N.KAOY
JNC 7
SBP mmHg
DBP mmHg
Normal
<120
and
<80
Prehypertension
120139
or
8089
Stage 1 Hypertension
140159
or
9099
Stage 2 Hypertension
>160
or
>100
Stage 1 Hypertension
(SBP 140 159 or DBP 90
99 mmHg)
Stage 2 Hypertension
(SBP > 160 or DBP > 100
mmHg)
GLB.IRB.06.10.09
BP Targets
JNC VII
ESH-ESC
WHO-ISH
<140/90
DM
<140/90
lower if tolerated
SBP <140
DM
renal
DM
Renal CVD
<130/80
<130/80
<130/80
Stage 2 Hypertension
(SBP >160 or DBP >100 mmHg)
2-drug combination for most
(usually thiazide-type diuretic and
ACEI, or ARB, CCB or (BB??)
Combination therapy:
ESH and JNC 7 accepted that most patients will need to use two or
more drugs in order to achieve goal BP
GLB.IRB.06.10.09
Diuretics
Betablockers
Angiotensinreceptor
blockers
Alphablockers
Calcium
channel
blockers
ACE
inhibitors
1:
Younger
(<55)
Older
(>55)
Renin
A or B
C or D
C or D
2:
3:
A or B
A or B
+
C or D
-blockers
AT1-receptor
blockers
1-blockers
Calcium
antagonists
ACE inhibitors
Pathophysiologic difference
Low renin
(Wet vasocontriction)
Arterioles
Higher
High
Low
Low
High
High
High
Low
Yes
Peripheral resistance
Aldosterone
Plasma volume
Cardiac output
Haematocrit
Blood urea
Blood viscosity
Tissue perfusion
Postural hypotension
High
Low to High
High
High
Low
Low
Low
High
No
Clinical examples
(+) Stroke
(+) Heart attack
(+) Renal damage
(+) Retinopathy encephalopathy
Vascular sequelae
(-)
(-)
(-)
(-)
Treatments
(-)
(-)
(+)
(+)
(+)
RAA
SNS
Heart rate and cardiac output
Sodium and water retention
Blood pressure
Atenolol + Thiazide
ASCOT Trial
BP Targets <140/90 m Hg or <130/80 mm Hg in Patients with Diabetes
Atenolol 50-100 mg
add
add
Perindopril 4-8 mg
add
Bendroflumethiazide-K
1.25 - 2.5 mg
Doxazosin 4-8 mg
Other medications
More than 50% in each group were on 2 or more medications; 26% crossed
over to other study drugs; 40%
*Lancet 2005;366:895
ASCOT
INVEST
CCB + perindorpil 4 to 8
mg (70%) vs. atenolol +
thiazide
(n = 9639 vs. 9618)
All cause
mortality
NS
11%
(p=0.0247)
NS
Combined
CHD
NS
13%
(p=0.007)
NS
Combined
CVD
NS
16%
(p=0.0001)
No data available
Stroke
NS
23%
(p=0.003)
NS
16%
(p=0.1257)
No data available
No data available
30%
(p<0.0001)
1.2%
(<p ?)
NS
S (HR 0.85%)
NS
Heart failure
New onset of
diabetes
New onset
renal
impairment
S in favor of
diuretic
CONCLUSION
JNC 7 and other guidelines provides
many guidance to the management of
hypertension
The ASCOT result MAY change the
guidelines
Perindopril makes the difference
between the ASCOT, ALLHAT and
INVEST results
ASCOT Trial*
Primary Objectives
To compare the effect on non-fatal
myocardial infarction (MI) and fatal CHD
of an antihypertensive regimen
based on a B-blocker +/- diuretic with a
regime based on a CCB +/- ACE-I
, Lancet 2005;366:895
ASCOT Trial*
ASCOT INVESTIGATORS
CONCLUSIONS
Contemporary
therapy [CCB/ACE]
is superior to older therapy
[BBL/Diuretic] in the management of
hypertension---
ASCOT Trial*
Stop-2- No difference in CV
outcome- Beta Blocker/diuretic
compared to ACE/CCB
ALLHAT.- Diuretic based RX
equal to or better than[ in some
subgroups] an ACE or CCB based
treatment group
SHEP-Diuretic based RX-elderly
marked reduction in CV events
compared to placebo
Vs
5 kelas anti hipertensi dapat secara setara sebagai 1stline treatment: initiation and maintenance....termasuk blockers !
(dengan pembatasan spt ;tidak direkomendasikan pada
pasien dengan metabolic syndrome atau resiko tinggi
diabetes).
Kombinasi -blocker + thiazide masih valid sebagai
alternatif terapi
secondary outcomes?
How much statistical manipulation
is acceptable to prove a point?
REBUTTAL
Criticisms of the
ALLHAT Conclusions
Conflicting Data
1. ALLHAT (favors a diuretic) Blinded
2. STOP-2
(equal outcomes B-BL/D vs CCB or ACE-I)
3. ASCOT
(different outcomes CCB/ACE-I vs B-BL/D)
4.VALUE
(CCB reduces MI events more than an ARB)
CRITICS
ALLHAT
Wrong add-on drugs
Demographics favored diuretics
Should have adhered to primary outcome results
BP differences accounted for difference in outcome
VALUE
Statistical manipulations to explain
results
ASCOT
Wrong comparator medication
Secondary analyses for conclusions?
Are the results generalizable?
CONCLUSIONS
Metoprolol
increasing
1-selectivity
1:20
no
selectivity
1.8:1
Propranolol
increasing
2-selectivity
300:1
ICI
118.551
Atenolol
Betaxolol
1:35
1:35
Thank You
For your kind attention