FOCUS ON ARB

Dr. I Gede Palgunadi, Sp.PD

1 September 2009
The World Health
Organisation (WHO)Estimates
Prevalence of Hypertension
That >20% of The Worlds
!"rrent #d"lt Pop"lation Has
Hypertension
BLOOD PRESSURE CONTROL
GOAL
GOAL
Less than 140/90 mm Hg
or
Less than 130/80 mm Hg
(diabetes)
or
Less than 125/75 mm Hg
(rotein !ria "1g/da#)
1999 WHO/ISH Hypertension Guidelines. J Hypertens 1999;17:151-183
! "osition St#te$ent. !i#%etes &#re '((';'5:S33-S)9
Total cases > 43 million adults
Prevalence of diabetes in Western
Pacific Region in 2003
International Diabetes Federation. Diabetes Atlas. 2
nd
Edition.
www.eatlas.idf.org. Accessed 27 October 2!!".
Australia
".2#
!.$ million
%ew &ealand
7."#
!.2 million
'(ina
2.7#
23.) million
Indonesia
*.$#
2.+ million
,ala-sia
$.4#
*.3 million
.a/an
".$#
".7 million
0(ili//ines
2.4#
*.! million
Ada/ted from 12O Diabetes 0rogramme Facts and Figures3
www.w(o.int4diabetes4facts4world5figures4en. Accessed * August 2!!".
Worldwide prevalence of
diabetes in 2000
%umber of /ersons
6 +!!!
+!!!774!!!
7+!!!734$!!!
3+!!!!7*4$$!!!
*+!!!!!74$$$!!!
> +!!!!!!
%o data a8ailable
Worldwide prevalence of
diabetes in 2030 (projected)
Total cases > 3!! million adults
%umber of /ersons
6 +!!!
+!!!774!!!
7+!!!734$!!!
3+!!!!7*4$$!!!
*+!!!!!74$$$!!!
> +!!!!!!
%o data a8ailable
Ada/ted from 12O Diabetes 0rogramme Facts and Figures3
www.w(o.int4diabetes4facts4world5figures4en. Accessed * August 2!!".
What is Diabetic Nephropathy?
Diabetic ne/(ro/at(- 9a term often used
interc(angeabl- wit( diabetic kidney disease
is a c(ronic /rogressi8e :idne- disease t(at de8elo/s
in ab!ut !ne t"ird of all /eo/le wit( diabetes
What is Diabetic Nephropathy?
The signs of diabetic nephropathy are: The signs of diabetic nephropathy are:
Rising urine albumin and protein excretion Rising urine albumin and protein excretion
Rising blood pressure Rising blood pressure
Declining kidney function Declining kidney function
This is associated with: This is associated with:
A greatly increased risk of cardiovascular A greatly increased risk of cardiovascular
disease disease
An increased risk of diabetic eye disease An increased risk of diabetic eye disease
(retinopathy) (retinopathy)
An increased risk of diabetic nerve damage An increased risk of diabetic nerve damage
(neuropathy) (neuropathy)
Screening of microalbuminuria in patients with type
2 DM
$orma% &i'roa%b!min(
!ria
)%ini'a% *o+ert,
nehroath#
24 h !rinar#
a%b!min (mg/da#)
-30 30(300 "300
.A/0 (g/min)
-20 20(200 "200
.rine a%b!min(
'reatinine ratio
-215 &a%es
-325 3ema%es
10(25 "25
!onnelly *!+ ,eun- J.&+ .#nnin- G. J Hypertens '((3;'1 /suppl 10:S7-S1'
4t!d# 5o!%ation 5re+a%en'e
.4A
1
6iabetes 297
Asian
2
6iabetes and
h#ertension
407
8nternationa%
(33 'o!ntries)
3
6iabetes 397
L89/
4
H#ertension and L:H 237
1. Jones & et #l. $ J 1idney !is '((';39:))5-59
'. Wu , et #l. !i#%etolo-i# '((5;)8:17-'2
3. "#r3in- HH et #l. 1idney Int /in press0
). 14eldsen S5 et #l. J. '((';'88:1)91-8
50/:AL/$)/ O9 &8)0OAL;.&8$.08A
Stage Stage Time after diagnosis of Time after diagnosis of
diabetes diabetes
Function Function
Normal Normal !"# years !"# years $ormal urine protein $ormal urine protein
excretion excretion
$ormal blood $ormal blood
pressure pressure
$ormal or high $ormal or high
kidney function kidney function
Early kidney Early kidney
disease disease
#!"# years #!"# years %icroalbuminuria %icroalbuminuria
Slight increase in Slight increase in
blood pressure blood pressure
$ormal kidney $ormal kidney
function function
Proteinuria Proteinuria "!& years "!& years 'igh levels of urine 'igh levels of urine
protein protein
'igh blood pressure 'igh blood pressure
Failing kidney Failing kidney
function function
End-stage disease End-stage disease "#!( years "#!( years )ery high urine )ery high urine
protein protein
)ery high blood )ery high blood
pressure pressure
*idney fail *idney fail
Stages in the development of diabetic nephropathy
,ETA;O<I' 2AE,OD=%A,I'
>lucose Flow 4 /ressure
?asoacti8e
(ormones
9egAII endot(elin@
0A'II
Ad8anced
gl-cation
'-to:ines
T>F ?E>F
E',
cross lin:ing
E',
E', A''B,B<ATIO%
?ascular /ermeabilit-
0COTEI%BCIA
,etabolic dan (aemod-namic /at(ogenesis
of diabetic ne/(ro/at(-
A$G8O</$48$ 0/)/5<O0 ;LO)=/0 ( A0; ) A$G8O</$48$ 0/)/5<O0 ;LO)=/0 ( A0; )
$e> 4tandard Anti(hiertensi 5er3orman'e $e> 4tandard Anti(hiertensi 5er3orman'e
A$G8O</$48$ 0/)/5<O0 ;LO)=/0 ( A0; ) A$G8O</$48$ 0/)/5<O0 ;LO)=/0 ( A0; )
$e> 4tandard Anti(hiertensi 5er3orman'e $e> 4tandard Anti(hiertensi 5er3orman'e
RENOROTE!T"ON

Ceduction of blood /ressure

Ceduction of albuminuria

%on blood /ressure de/endent action of

CAAD bloc:ade
J Am oc !ep"rol #3$202%20&' 2002
Formation of
Angiotensin and
organs effected b-
t(eir actions
% Eng . ,ed ?ol. 334
%O. 2+E *$$"
/?erent " a?erent arterio%ar di%atation
A?erent " e?erent arterio%ar di%atation
G%omer!%ar 'ai%%ar# ress!re
(5G))
G%omer!%ar 'ai%%ar# ress!re
(5G))
Calcium Channel
Blockers
ACE inhibitors
6olins J"+ *#i4 7. Se$in 8ep9rol 1991;11:538-)8
#T $ #T $
#""R%
#T & #T &
A'E in(ibitor
Ang
Ang
'(-mase
Ang ;rad-:inin
%O
0>I2
?asoconstriction
Cenal sodium reabso/tion
Aldosteron secretion
D-m/at(etic acti8ation
'ell growt( and /roliferation
?asodilatation
Anti/roliferation
A/o/tosis
=86$/@ 50O</)<8O$ /99/)<
=86$/@ 50O</)<8O$ /99/)<
O9 A$G8O</$48$ 0/)/5<O0
O9 A$G8O</$48$ 0/)/5<O0
;LO)=/04
;LO)=/04
=86$/@ 50O</)<8O$ /99/)<
=86$/@ 50O</)<8O$ /99/)<
O9 A$G8O</$48$ 0/)/5<O0
O9 A$G8O</$48$ 0/)/5<O0
;LO)=/04
;LO)=/04
A PRogram for Irbesartan Mortality and Morbidity Evaluation
Parving (%(' et al) N Engl J Med 200#*3+,$-&0%-&-)
A PRogram for Irbesartan Mortality and Morbidity Evaluation
Ob'ective :

To e8aluate t(e AIICA irbesartan (as reno/rotecti8e

effects inde/endent of its im/act on s-stemic ;0 in
(-/ertensi8e t-/e 2 diabetic /atients wit(
/ersistent microalbuminuria
St(dy Design :

,ulticenter randomiFed doubleGblind /laceboG

controlled com/arison or irbesartan *+! mg and 3!!
mg 8ersus control 9/lacebo /lus ot(er
anti(-/ertensi8e agents eHcluding A'E in(ibitors
AIICAs and di(-dro/-ridine '';s@.

+$! /atients wit( t-/e 2 diabetes microalbuminuria

92!G2!! g4min@ normal renal function and
(-/ertension were followed for an a8erage of 2 -ears.
rimary Endpoint :

Time to first occurrence of clinical

/roteinuria 9diabetic ne/(ro/at(-@ defined
as albumin eHcretion rate 9AEC@ > 2!! g4min
and an increase in AEC of at least 3!# from
baseline at 2 successi8e e8aluations
Secondary Endpoints :

O8ernig(t AEC c(anges

Estimated creatinine clearance c(anges

Cegression to normoalbuminuria 96 2! g4min@

at 2 -ears 9#@
RES)*TS :

Dignificant reduction in t(e /rogression to

clinical /roteinuria

Dignificant increase in t(e number of /atients

regressing to normoalbuminuria 934# irbesartan
3!! mgE 2*# controlE /I!.!!"@

Dimilar le8els of ;0 reduction across all

treatment arms

Irbesartan was safe and well tolerated

33
0
,
#0
#,
20
0 3 . #2 #- 22 2+
/ollow%0p (mo)
0bjects
(1)
2ontrol
3rbesartan #,0 mg
3rbesartan 300 mg
0rimar- End/oint Anal-sis in IC,A 2
Time to First Occurrence of 'linical 0roteinuria
Parving (%(' et al) N Engl J Med 200#*3+,$-&0%-&-)
A PRogram for Irbesartan Mortality and Morbidity Evaluation
Ob'ective :

To determine w(et(er t(e in(ibition of angiotensin II

acti8it- wit( t(e AIICA irbesartan alters t(e
/rogression of t-/e 2 diabetic ne/(ro/at(-
inde/endent of its im/act on s-stemic ;0
St(dy Design :

,ulticenter randomiFed doubleGblind /laceboG

controlled com/arison or irbesartan t(e '';
amlodi/ine and control 9/lacebo /lus ot(er
anti(-/ertensi8e agents eHcluding A'E in(ibitors
AIICAs and di(-dro/-ridine '';s@.

*7*+ /atients wit( t-/e 2 diabetes /roteinuria $!!

mg4d and (-/ertension were followed for an a8erage
of 2 -ears.
rimary Endpoint :

Time to t(e doubling of baseline serum

ceratinine 9De'r@ le8elE or endGstage renal
disease 9EDCD@ defined as t(e need for
dial-sis or renal trans/lant or De'r > ".!
mg4d<@E or allGcause mortalit-
Secondary Endpoints:
Time to com/osite end/oint of fatal or nonfatal '?
e8ents

'? deat(

%onfatal ,I

2os/italiFation for (eart failure

0ermanent neurologic deficit due to stro:e

Abo8eGt(eGan:le am/utation
Res(lts :

Dignificant reduction in t(e /rogression of diabetic

ne/(ro/at(-

Dignificant reduction in t(e ris: of '? e8ents

across all treatment arms

Dignificant reduction in (os/italiFation due to (eart

failure 8s amlodi/ine 9P6!.!!*@

Dimilar le8el of ;0 reduction across all treatment

arms

Irbesartan was safe and well tolerated

0bject
s (1)
0 . #2 #- 2+ 30 3. +2 +- ,+
/ollow%0p (mo)
.0
0
#0
20
30
+0
,0
.0
&0
rimary Endpoint #nalysis in "DNT
Time to Doubling of Derum 'reatinine EDCD or Deat(
3rbesartan
Amlodipine
2ontrol
4ewis 5J et al) N Engl J Med 200#*3+,$-,#%-.0)
CCC 2!#
PI!.!2
PI%D
CCC 23#
PI!.!!"
!ON!*)S"ON
T(e results of 0CI,E demonstrate t(at t(e
AIICA IC;EDACTA% (as /rotecti8e effects for
/atients wit( (-/ertension and t-/e 2
diabetes at earl- and late stages of renal
disease inde/endent of t(e effects on ;0.