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Thursday, August 21, 2014

100 patients with eGFR < 60


(Wednesday afternoon in Outpatients)
Thursday, August 21, 2014

Wednesday afternoon, 1 year later: 1 patient needs RRT, 10


patients have died (> 50% CV death)
Thursday, August 21, 2014

Wednesday afternoon, 10 years later: 8 patients need RRT, 65


patients have died, 27 have ongoing CKD
6
The Prevalence of Hypertension & DM in Indonesia

Age (year) Prevalence (%)


Hypertension DM
18 – 24 12.2 0.6
25 – 34 19.0 1.8
35 – 44 29.9 10.5
45 – 54 42.2 13.5
55 – 64 53.7 14.5
65 – 74 63.3 10.7
All 31.7 5.6

RisKesDas 2007
Diabetic nephropathy is the leading cause of ESRD

Diabetes
160
Hypertension
Incidence per million population

140 Glomerulonephritis
Cystic kidney
120
100
80
60
40
20
0
1980 1985 1990 1995 2000
Year
Brewster, Perazella. Am J Med 2004; 116:263-272
The Continuum of Diseases

Kidney Diseases Cardiovascular Diseases

Dialysis Heart Failure


End-Stage

GFR  Progression CVD events

Damage ; Proteinuria Initiation CAD ; LVH

Diabetes Diabetes
Hypertension Increase Risk Hypertension
Hyperlipidemia Hyperlipidemia
Majority of Hypertensive Patients Not at SBP Goal of
<140 mm Hg: Goal Gap

14.0

12.0

10.0

Population 8.0
(millions)
6.0
73% NOT
4.0 MEETING
GOAL
2.0

0.0
91–100

131–140

231–240
141–150

151–160

161–170

171–180

181–190

241–250
121–130
111–120

221–230
191–200

201–210
101–110
81–90

211–220
SBP Range (mm Hg)
SBP = Systolic Blood Pressure
Adapted from Whyte JL et al. J Clin Hypertens. 2001;3:211-216.
JNC 7: CVD Risk Factors

• Hypertension*
• Cigarette smoking
• Obesity* (BMI >30 kg/m2)
• Physical inactivity
• Dyslipidemia*
• Diabetes mellitus*
• Microalbuminuria
• estimated GFR <60 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.

JAMA 2003:289:2560
Adapted from Dzau V, et al.
Am Heart J. 1991;2(4 pt
1):1244-1263.
Identifiable Causes of Hypertension

 Sleep apnea
 Drug-induced or related causes
 Chronic kidney disease
 Primary aldosteronism
 Renovascular disease
 Chronic steroid therapy and Cushing’s syndrome
 Pheochromocytoma
 Coarctation of the aorta
 Thyroid or parathyroid disease
JNC 7 Express. JAMA. 2003 Sep 10; 290(10):1314
Causal Factors for Hypertension

 Excess over weight or obese


 Excess dietary sodium
 Mean intake: Men 4100 mg; Women 2750 mg
 75% from processed foods
 Reduced physical activity
 Inadequate fruit, vegetable and potassium
intake
 Excess alcohol consumption

Hypertension 2003;289:2560-2572.
Endothelial cells

Angiotensinogen Angiotensin II
Blood
vessel
Aldosteron
Angiotensin I ACE
Renin
Kininogen Angiotensinogen
kallikrein renin

Bradykinin (BK) Angiotensin

endopeptides
BKB receptor

Ang (1 – 7)
Inactive
Vasodilation peptides
NO
ACE
prostaglandins
A (1-7)
EDHF receptor
Inactive
tPA AT1 AT2 AT3 AT4 Peptides
receptors receptors receptors receptors
Vasodilation
Antiproliferation
Oxidation Vasodilation ? Vascular
Vasoconstriction Antiproliferation integrity
Proliferation Apoptasis
Matrix Formation
PAI-1
Aldosterone Prolong stimulation
Secretion leads to deleterious
effects
Angiotensin II Plays a Central Role in Organ Damage

Atherosclerosis* Stroke
Vasoconstriction
Vascular hypertrophy
Endothelial dysfunction Hypertension

LV hypertrophy
A II Fibrosis
Remodeling Heart failure DEATH
Apoptosis MI

GFR
Proteinuria
Renal failure
Aldosterone release
Glomerular sclerosis
*preclinical data
LV = left ventricular; MI = myocardial infarction; GFR = glomerular filtration rate

Adapted from Willenheimer R et al Eur Heart J 1999; 20(14): 9971008, Dahlöf B J Hum Hypertens 1995; 9(suppl 5): S37S44, Daugherty A et al J Clin
Invest 2000; 105(11): 16051612, Fyhrquist F et al J Hum Hypertens 1995; 9(suppl 5): S19S24, Booz GW, Baker KM Heart Fail Rev 1998; 3: 125130,
Beers MH, Berkow R, eds. The Merck Manual of Diagnosis and Therapy. 17th ed. Whitehouse Station, NJ: Merck Research Laboratories 1999:
16821704, Anderson S Exp Nephrol 1996; 4(suppl 1): 3440, Fogo AB Am J Kidney Dis 2000; 35(2):179188 18
Algorithm for Treatment of Hypertension

Lifestyle Modifications

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


(<130/80 mmHg for those with diabetes or chronic kidney disease)

Initial Drug Choices

Without Compelling With Compelling


Indications Indications

Stage 1 HTN (SBP 140–159 or Stage 2 HTN (SBP >160 or DBP Drug(s) for the compelling
DBP 90–99 mmHg) >100 mmHg) indications
Thiazide-type diuretics for most. 2-drug combination for most Other antihypertensive drugs
May consider ACEI, ARB, BB, (usually thiazide-type diuretic and (diuretics, ACEI, ARB, BB, CCB)
CCB, or combination. ACEI, or ARB, or BB, or CCB) as needed.

Not at Goal
Blood Pressure
Optimize dosages or add additional drugs
until goal blood pressure is achieved.
Consider consultation with hypertension specialist.

JNC 7 Express. JAMA. 2003 Sep 10; 290(10):1314


Lifestyle Modification
Approximate SBP Reduction
Modification
(range)
Weight reduction 5-20 mmHg/ 10 kg weight loss

Adopt DASH eating plan 8-14 mmHg

Dietary sodium reduction 2-8 mmHg

Physical activity 4-9 mmHg

Moderation of alcohol
2-4 mmHg
consumption
JNC 7 Express. JAMA. 2003 Sep 10; 290(10):1314
The Diabetes Epidemic

189 mill. in 2003


324 mill.estimated for 2025
72% increase

38.2
44.2
16% 81.8
25.0 156.1
39.7 91%
59%
18.2
35.9
13.6 97%
26.9
10.4 98%
19.7
1.1
88%
1.7
59%

From Zimmet P et al. Diabet Med. 2003;20:693-702.


Development and progression of Type 2 Diabetes

350
300
Glucose

250 Post Prandial Glucose


mg/dl

200
150
100 Fasting Glucose
50
Relative Function

250
200 Insulin Resistance
%

150
100
50 Insulin Level
Beta cell failure
0
-10 -5 0 5 10 15 20 25 30
Years of Diabetes
Adapted from R.M. Bergenstal, International Diabetes Center
Association of Systolic Blood Pressure (SBP) and CV
Death in Type 2 Diabetes

250
225 No diabetes
(deaths/10,000 person-years)

Diabetes
200
175
CV Mortality

150
125
100
75
50
25
0
120 120–139 140–159 160–179 180–199 200

SBP (mm Hg)

Adapted from Stamler J et al. Diabetes Care. 1993;16:434-444.


Cardiovascular Disease in Type 2 Diabetes:
Convergence of Multiple Pathogenetic Mechanisms

Libby P and Plutzky J, Circulation 2002;106:2760-63


Natural History of Type 2 Diabetic Nephropathy

Clinical type 2 diabetes

Functional changes*

Structural changes*

Rising blood pressure

Microalbuminuria

Proteinuria

Rising serum creatinine levels

End-stage renal disease

Cadiovascular death

Onset of diabetes 2 5 10 20 30
Years
* Renal hemodynamics altered, glomerular hyperfiltration.
† Glomerular basement membrane thickening ,

mesangial expansion , microvascular changes +/-.


Antidiabetic mechanisms of angiotensin-converting enzyme inhibitors
and angiotensin II receptor antagonists: beyond the renin-angiotensin
system

Angiotensin II receptor
blockers
Activation Blockade

PPAR-γ Angiotensin
pathways pathways

Insulin Cell Cell Oxidative


resistance inflammation proliferation stress

Dyslipidemia Hypertension

Inhibition of
atherosclerosis
Kurtz TW, Pravenec M. J Hypertens 2004;22: 2253
• JNC 8 or the 2014 Evidence-Based Guideline for the Management
of High Blood Pressure in Adults was released in December
• James PA, Oparil S, Carter BL, et al. 2014 Evidence-based guideline for the management of
high blood pressure in adults: Report from the panel members appointed to the Eighth Joint
National Committee (JNC 8). JAMA 2014; DOI:10.1001/jama.2013.284427. Available at:
http://jama.jamanetwork.com/journal.aspx

• The American Society of Hypertension (ASH) and International


Society of Hypertension (ISH) also issued a separate document
entitled, “Clinical Practice Guidelines for the Management of
Hypertension in the Community
• Weber MA, Schiffrin EL, White WB, et al. Clinical practice guidelines for the management of
hypertension in the community. A statement by the American Society of Hypertension and the
International Society of Hypertension. J Clin Hypertens 2013; DOI:10.1111/jch.12237.
Available at http://www.ash-us.org/documents/ASH_ISH-Guidelines_2013.pdf . J Hypertens
2014; 32:3-15
JNC 8

Addressed 3 high priority questions:

• 1. In adults with hypertension, does initiating antihypertensive pharmacologic


therapy at specific BP thresholds improve health outcomes?

• 2. In adults with hypertension, does treatment with antihypertensive


pharmacologic therapy to a specified BP goal lead to improvements in health
outcomes?

• 3. In adults with hypertension, do various antihypertensive drugs or drug


classes differ in comparative benefits and harms on specific health
outcomes?

The panel undertook “a rigorous, evidence-based approach to recommend


treatment thresholds, goals and medications” in hypertension management in
adults
JNC 8 recommendations:
Recommendation 1
– In the general population aged >60 years, initiate pharmacologic
treatment to lower blood pressure (BP) at systolic blood pressure (SBP)
>150 mmHg or diastolic blood pressure (DBP) >90mmHg and treat to a
goal SBP <150 mm Hg and goal DBP <90 mm Hg. (Strong
Recommendation – Grade A)
Corollary Recommendation
– In the general population aged >60years, if pharmacologic treatment for
high BP results in lower achieved SBP (eg, <140mmHg) and treatment
is well tolerated and without adverse effects on health or quality of life,
treatment does not need to be adjusted. (Expert Opinion – Grade E)
Recommendation 2
– In the general population <60 years, initiate pharmacologic treatment to
lower BP at DBP >90mmHg and treat to a goal DBP <90mmHg. (For
ages 30-59 years, Strong Recommendation – Grade A; For ages 18-29
years, Expert Opinion – Grade E)
JNC 8 recommendations: cont….
Recommendation 3
– In the general population <60 years, initiate pharmacologic treatment to
lower BP at SBP >140mmHg and treat to a goal SBP <140mmHg.
(Expert Opinion – Grade E)
Recommendation 4
– In the population aged >18 years with chronic kidney disease (CKD),
initiate pharmacologic treatment to lower BP at SBP >140mmHg or DBP
>90 mmHg and treat to goal SBP<140mmHg and goal DBP<90mmHg.
(Expert Opinion – Grade E)
Recommendation 5
– In the population aged >18years with diabetes, initiate pharmacologic
treatment to lower BP at SBP >140mmHg or DBP >90mmHg and treat
to a goal SBP <140mmHg and goal DBP <90mmHg. (Expert Opinion –
Grade E)
JNC 8 recommendations: cont…
Recommendation 6
– In the general nonblack population, including those with diabetes, initial
antihypertensive treatment should include a thiazide-type diuretic,
calcium channel blocker (CCB), angiotensin-converting enzyme inhibitor
(ACEI), or angiotensin receptor blocker (ARB). (Moderate
Recommendation – Grade B)
Recommendation 7
– In the general black population, including those with diabetes, initial
antihypertensive treatment should include a thiazide-type diuretic or
CCB. (For general black population: Moderate Recommendation –
Grade B; for black patients with diabetes: Weak Recommendation –
Grade C)
Recommendation 8
– In the population aged >18 years with CKD, initial (or add-on)
antihypertensive treatment should include an ACEI or ARB to improve
kidney outcomes. This applies to all CKD patients with hypertension
regardless of race or diabetes status. (Moderate Recommendation –
Grade B)
JNC 8 recommendations: cont…
Recommendation 9
– The main objective of hypertension treatment is to attain and maintain
goal BP.
– If goal BP is not reached within a month of treatment, increase the dose of
the initial drug or add a second drug from one of the classes in
recommendation 6 (thiazide-type diuretic, CCB, ACEI, or ARB).
– The clinician should continue to assess BP and adjust the treatment
regimen until goal BP is reached.
– If goal BP cannot be reached with 2 drugs, add and titrate a third drug
from the list provided. Do not use an ACEI and an ARB together in the
same patient.
– If goal BP cannot be reached using only the drugs in recommendation 6
because of a contraindication or the need to use more than 3 drugs to
reach goal BP, antihypertensive drugs from other classes can be used.
– Referral to a hypertension specialist may be indicated for patients in whom
goal BP cannot be attained using the above strategy or for the
management of complicated patients for whom additional clinical
consultation is needed. (Expert Opinion – Grade E)
Continue in next slide
JNC 8 Summary

• BP goal for >60 y.o. <150/90 mmHg


• BP goal of <140/90 mmHg for <60 y.o.
• BP goal of <140/90 mmHg for adults with diabetes and
non-diabetic chronic kidney disease
• Initial pharmacologic treatment with ACEi, ARB, CCB or
thiazide-type diuretic in non-black population
• In persons with CKD and hypertension, initial or add on
therapy with either ACEi or ARB
• 3 titration strategies: (choose from any of the 4 classes)
• Note that ACEi and ARB should not be combined
– Maximize 1st medication before adding a 2nd
– Add second medication before reaching max dose of 1st
ACEi- angiotensin converting
– Start 2 medication separately or as FDC enzyme inhibitor
ARB – angiotensin receptor
blocker
CCB – calcium channel blocker
FDC – fixed dose combination
Blood pressure management
in CKD ND without DM (KDIGO-CPG 2012)

1. We recommend that adults with diabetes


and CKD ND with urine albumin excretion <
30 mg per 24 hours whose office BP is
consistently > 140 mmHg systolic or > 90
mmHg diastolic be treated with BP-
lowering drugs to maintain a BP that is
consistently ≤ 140 mmHg systolic and ≤ 90
mmHg diastolic. (1B)
Blood pressure management
in CKD ND without DM (KDIGO-CPG 2012)

2. We suggest that non-diabetic adults with


CKD ND and urine albumin excretion of 30
to 300 mg per 24 hours whose office BP is
consistently > 130 mmHg systolic or > 80
mmHg diastolic be treated with BP-
lowering drugs to maintain a BP that is
consistently ≤ 130 mmHg systolic and ≤
80 mmHg diastolic. (2D)
Blood pressure management
in CKD ND without DM (KDIGO-CPG 2012)

3. We suggest that non-diabetic adults


with CKD ND and urine albumin
excretion > 300 mg per 24 hours
whose office BP is consistently >130
mmHg systolic or > 80mmHg diastolic
be treated with BP-lowering drugs to
maintain a BP that is consistently
≤130 mmHg systolic and ≤80 mmHg
diastolic. (2C)
Blood pressure management
in CKD ND without DM (KDIGO-CPG 2012)

4. We suggest that an ARB or ACE-I be


used in non-diabetic adults with CKD
ND and urine albumin excretion of 30
to 300 mg per 24 hours in whom
treatment with BP-lowering drugs is
indicated. (2D)
Blood pressure management
in CKD ND without DM (KDIGO-CPG 2012)

5. We recommend that an ARB or ACE-I be


used in non-diabetic adults with CKD ND
and urine albumin excretion
> 300 mg per 24 hours in whom
treatment with BP-lowering drugs is
indicated. (1B)
Blood pressure management
in CKD ND with DM (KDIGO-CPG 2012)

1. We recommend that adults with diabetes


and CKD ND with urine albumin excretion
o30 mg per 24 hours whose office BP is
consistently >140mmHg systolic or
>90mmHg diastolic be treated with BP-
lowering drugs to maintain a BP that is
consistently ≤140mmHg systolic and ≤
90mmHg diastolic. (1B)
Blood pressure management
in CKD ND with DM (KDIGO-CPG 2012)

2. We suggest that adults with diabetes and


CKD ND with urine albumin excretion >30
mg per 24 hours whose office BP is
consistently >130mmHg systolic or
>80mmHg diastolic be treated with BP-
lowering drugs to maintain a BP that is
consistently ≤130mmHg systolic and
≤80mmHg diastolic. (2D)
Blood pressure management
in CKD ND with DM (KDIGO-CPG 2012)

3. We suggest that an ARB or ACE-I be


used in adults with diabetes and CKD
ND with urine albumin excretion of 30
to 300 mg per 24 hours (2D)
4. We recommend that an ARB or ACE-I be
used in adults with diabetes and CKD ND
with urine albumin excretion
> 300 mg per 24 hours (1B)
Endothelial cells

Angiotensinogen Angiotensin II
Blood
vessel
Aldosteron
Angiotensin I ACE
Renin
Kininogen Angiotensinogen
kallikrein renin

Bradykinin (BK) Angiotensin

endopeptides
BKB receptor

Ang (1 – 7)
Inactive
peptides
Ang II
Vasodilation
NO
ACE
prostaglandins
A (1-7)
EDHF receptor
Inactive
tPA AT1 AT2 AT3 AT4 Peptides
receptors receptors receptors receptors
Vasodilation
Antiproliferation
Oxidation Vasodilation ? Vascular
Vasoconstriction Antiproliferation Integrity
Proliferation Apoptasis
Matrix Formation
Aldosterone Prolong stimulation PAI-1
Secretion leads to deleterious
effects
AT1R-Blockade and Insulin Sensitivity

Irbesartan improves Insulin-Sensitivity in ZDF-Rats

Irbesartan
increased
Glucose uptake
in skeletal
muscle

Henriksen et al., Hypertension 2001


Endothelial function
And inflammatory
parameters after a
high-fat load in type
2 diabetic patients
(n=20)

Ceriello A et al., Circulation 2005, 111: 2518-24


Recommendations:
Hypertension/Blood Pressure Control
Goals
• People with diabetes and hypertension should be treated to
a systolic blood pressure goal of <140 mmHg (B)
• Lower systolic targets, such as <130 mmHg, may be
appropriate for certain individuals, such as younger
patients, if it can be achieved without undue treatment
burden (C)
• Patients with diabetes should be treated to a diastolic blood
pressure <80 mmHg (B)

ADA. VI. Prevention, Management of Complications. Diabetes Care 2013;36(suppl 1):S29.


IRMA-2 Study Design : Irbesartan in Patients with Early
Renal Disease

590 patients (mean age 58 years) with type 2 diabetes,


microalbuminuria (albumin excretion rate 20–200 g/min),
normal renal function, and hypertension

Screening/Enrollment Double-blind Treatment

Placebo
n = 201

Irbesartan 150 mg
n = 195

Irbesartan 300 mg
n = 194

Up to 5 weeks Follow-up: 2 years


Parving H-H et al. N Engl J Med 2001;345: 870–8.
IRMA-2 Results: Consistent Blood Pressure Response

160 Control SeSBP


Irbesartan 150 mg SeSBP
150 Irbesartan 300 mg SeSBP
140
130
Mean SeSBP 120
and SeDBP 110
(mm Hg) Control SeDBP
100 Irbesartan 150 mg SeDBP
90 Irbesartan 300 mg SeDBP
80
70
0
0 3 6 9 12 15 18 21 24 27
Months
Concomitant antihypertensive agents received by 56% of patients in the
control group, 45% in the irbesartan 150 mg group, and 43% in the
irbesartan 300 mg group. Parving H-H et al. N Engl J Med 2001;345: 870–8.
IRMA-2 Results: Irbesartan Significantly Delays
Progression To Overt Proteinuria

Primary endpoint: Time to overt proteinuria


20
Control n = 201
Irbesartan 150 mg n = 195
15 Irbesartan 300 mg n = 194
Subjects
(%)
10

0
0 3 6 12 18 22 24
Follow-up (months)

Parving H-H et al. N Engl J Med 2001;345: 870–8.


IRMA-2 Results: Irbesartan Reduces Incidence of Overt
Proteinuria

RRR=70%
p<0.001
18 RRR=39%
p=0.08
16 14.9
14
Subjects with 12
Overt 9.7
10
Proteinuria
(%) 8
6 5.2
4
2
0
Control 150 mg 300 mg
(n=201) (n=195) (n=194)
Irbesartan
Parving H-H et al. N Engl J Med 2001;345: 870–8.
IRMA-2 Results: Irbesartan Normalizes Urinary Albumin
Excretion

45 p=0.006
40
35 34
30
Subjects 24
25
(%) 21
20
15
10
5
0
Control 150 mg 300 mg
(n=201) (n=195) (n=194)
Irbesartan
Parving H-H et al. N Engl J Med 2001;345: 870–8.
IRMA-2: Early Use of Irbesartan is Renoprotective in Hypertensive
Type 2 Diabetes Patients with Microalbuminuria

• Irbesartan is renoprotective in hypertensive patients with


type 2 diabetes and microalbuminuria,
– Regression to normoalbuminuria was more frequent with
irbesartan 300 mg
• The renoprotective effect of irbesartan is independent of its
blood pressure-lowering effect
• Irbesartan has a good safety/tolerability profile
– Fewer non-fatal CV events, serious AEs, and discontinuations
due to AEs in the irbesartan groups

70% risk reduction in the progression from microalbuminuria


to overt proteinuria with irbesartan 300 mg

Parving H-H et al. N Engl J Med 2001;345: 870–8.


IDNT Study: Irbesartan in Patients with Late Renal
Disease Study Design

1,715 patients (mean age 59 years) with type 2 diabetes,


nephropathy (proteinuria 900 mg/d), and hypertension
Double-blind Treatment

Irbesartan*
Screening/Enrollment n = 579

Placebo*
n = 569
Up to 5 weeks

Amlodipine*
n = 567
Minimum follow-up:
approximately 2 years
(average 3 years)
* Adjunctive antihypertensive therapies (excluding ACE
inhibitors, angiotensin II receptor antagonists, and calcium
channel blockers) added to each arm to achieve equal
blood pressure reduction Lewis EJ et al. N Engl J Med 2001; 345: 851–860.
IDNT: Irbesartan Produces A Consistent Blood
Pressure Response

160 Irbesartan
Amlodipine
SBP Control
140

BP
(mm Hg) 120 Patients received 3.0 concomitant
antihypertensive agents in the irbesartan
and amlodipine groups, and 3.3
Mean concomitant agents in the control group.
100

DBP
80

0 6 12 18 24 30 36 42 48 54

Follow-up visit (mo)


Lewis EJ et al. N Engl J Med 2001; 345: 851–860.
IDNT Results: Irbesartan Reduces the Progression of
Diabetic Nephropathy (Combined Endpoint)

IDNT primary endpoint: Time to doubling of serum creatinine, ESRD, or death


70
Irbesartan
n = 579 RRR 23%
60 p=0.006
RRR 20%
Amlodipine p=0.02
n = 569
50 p=NS

Control
Subjects 40 n = 567

(%)
30

20

10

0
0 6 12 18 24 30 36 42 48 54 60
Follow-up (mo)
Lewis EJ et al. N Engl J Med 2001; 345: 851–860.
IDNT Results: Irbesartan Significantly Reduces the
Time to ESRD

40

Irbesartan
n = 579
RRR 23%
n = 567
30 Control +
p=0.04

Subjects amlodipine
n = 569
(%)
20

10

0
0 6 12 18 24 30 36 42 48 54 60
Follow-up (months)

Lewis EJ et al. N Engl J Med 2001; 345: 851–860.


The role of irbesartan in the treatment of diabetic
kidney disease
Time to renal endpoint by treatment assignment
(Doubling of serum creatinine or ESRD)

Irbesartan RRR = 34%


0.6 n = 579
p = 0.0002 RRR = 26%
Patients Amlodipine
reaching 0.5 n = 569 RRR = -12% p = 0.011
Scr Placebo p = 0.32
doubling n = 567
0.4
or ESRD
(fraction)
0.3

0.2

0.1

0.0

0 6 12 18 24 30 36 42 48 54 60 66 72 78
Follow-up time (months)
Lewis EJ et al. N Engl J Med 2001; 345: 851–860.
SUMMARY
 Lower is better and Earlier is better
 Clinical benefits occur in patients with hypertension when BP
is lowered to optimal levels.

 Irbesartan is renoprotective in hypertensive patients with type


2 diabetes and microalbuminuria

 70% risk reduction in the progression from microalbuminuria


to overt proteinuria with irbesartan 300 mg

 There was a significant improvement in blood pressure and


metabolic risk factors as a results of Irbesartan treatment.