HYPERTENSIONUnmet Needs in the Treatment of

A Major CV Risk Factor

HYPERTENSIONOne of the easiest conditions to diagnose

HOWEVER, UNCONTROLLED HYPERTENSION IS ASYMTOMATIC

Uncontrolled hypertension may be asymptomatic but can result in much CV morbidity & mortality

Impact of Hypertension and other risk factors

End-stageRenal Disease

CoronaryHeart Disease

Stroke

Heart failure

Left VentricularHypertrophy

Atherosclerosis

PersistentlyElevated BP

With every double digit increase in BP, risk of

CV Mortality doubles as well

0

2

4

6

8

10

115/75 135/85 155/95 175/105SBP/DBP (mmHg)

Lewington et al. Lancet. 2002;360:1903–1913.

Risk of CV Mortality Doubles With Each 20/10 mmHg BP Increase

Fold

incr

ease

in

rela

tive

CV ri

sk

1-fold2-fold

4-fold

8-fold

2 mmHg decrease in mean SBP

10% reduction in risk of stroke mortality

7% reduction in risk of IHD and other vascular disease mortality

Each 2 mmHg Decrease in SBP Reduces CV Risk by 7–10%

Lewington et al. Lancet. 2002;360:1903–1913.

Most patients with hypertension will require two

or more anti-hypertensive medications to achieve their

BP goals

Several Guidelines Acknowledge That Most

Patients Need Combination Therapy to Achieve BP Goals

Several Guidelines Acknowledge That Most Patients Need Combination Therapy to Achieve BP Goals

Combination treatment should be considered as first choice when there is CV high risk

Several Guidelines Acknowledge That Most Patients Need Combination Therapy to Achieve BP Goals

Many patients will require more than one drug to achieve adequate BP control

Even JNC-8 guidelines recommend use of Combination Therapy where:

SBP is over 160mmHg or 20mmHg above target BP

and/or

DBP is over 100mmHg or 10mmHg above target BP

JNC

Patie

nts w

ith B

P co

ntro

l (%

)

0

10

20

30

40 39%

20%

BP < 140/90 mmHg BP < 135/85 mmHg

Dickerson et al. Lancet. 1999:353:2008–2013.

Only Minority of Hypertensive Patients achieved BP Control through Monotherapy

Average number of antihypertensive medications1 2 3 4

Trial (SBP achieved)

ASCOT-BPLA (137 mmHg)

ALLHAT (138 mmHg)

IDNT (138 mmHg)

RENAAL (141 mmHg)

UKPDS (144 mmHg)

ABCD (132 mmHg)

MDRD (132 mmHg)

HOT (138 mmHg)

AASK (128 mmHg)

Several Trials Advocate Use of Combination to Achieve BP Goals

Bakris et al. Am J Med. 2004;116(5A):30S–38S;Dahlöf et al. Lancet. 2005;366:895–906.

IN PAKISTAN, THE BIGGEST AND MOST PREFFERED COMBINATION

IS ‘ARBs plus CCBs

BUT What’s the reason for preference of ARB plus CCB Combination?

CCB Induced Peripheral Edema minimized by ARB

1

Renal Hyperfiltration Induced by CCB is Reduced by ARB

DecreasedGlomerular pressure

and filtration

Amlodipine + Telmisartan

L-type Cachannels

IncreasedGlomerular pressure

and filtration

L-type Cachannels

Peti-Peterdi; Abstract ESC 2010 (submitted).

Amlodipine

2

Calcium channel blockade results in compensatory activation of the SNS, which, in turn, activates the renin angiotensin system (RAS).

These effects tend to attenuate the BP-lowering efficacy of CCBs. Administering an ARB counteracts these effects by blocking the RAS, which in turn decreases SNS activity.

Because CCBs have diuretic and natriuretic properties, they induce a state of negative sodium balance. This reinforces the antihypertensive effects of ARBs.

3 Synergistic Anti-Hypertensive Effect of ‘ARB plus CCB’ Combination

1.CCB Induced

Peripheral Edema is minimized by

ARB

2.Renal Hyper

filtration Induced by CCB is Reduced

by ARB

3.Synergistic

Anti-Hypertensive Effect of ‘ARB plus CCB’ Combination

Why Telmisartan plus Amlodipine?

Amlodipine has the Longest Plasma Elimination Half-life in its Class (CCB)

0

5

10

15

20

25

30

35

57

9

1214

16

19

> 30

Based on available online product information.

Plas

ma

elim

inati

on h

alf-l

ife (h

)

Lercani-dipine

Nife-dipine

Nimo-dipine

Nisol-dipine

Nicar-dipine

Felo-dipine

Laci-dipine

Amlo-dipine

0

6

12

18

24

78

9

12

15 15

24

Plas

ma

elim

inati

on h

alf-l

ife (h

ours

)

Epro-sartan

Lo-sartan

Val-sartan

Cande-sartan

Olme-sartan

Irbe-sartan

Telmi-sartan

Telmisartan has the Longest Plasma Elimination Half-life in its Class (ARBs)

Based on available online product information.

0

20

40

60

80

100

120

913

17 17

34

93

120

Volu

me

of d

istrib

ution

(litr

es)

Most lipophilic(high tissue penetration)

500

Cande-sartan

Epro-sartan

Val-sartan

Olme-sartan

Lo-sartan

Irbe-sartan

Telmi-sartan

500

Telmisartan also has the highest volume of Distribution amongst all ARBs

Based on available online product information.

Irbesartan Candesartan Losartan Olmesartan Valsartan Telmisartan

Renal Excretion 20% 40% 35% 40% 31% Less than 2%

Most favorable for patients with Renal

Impairment

Telmisartan has least excretion through renal route amongst all ARBs

Based on available online product information.

Telmisartan is the Most Studied Amongst ARBs in Mortality and Morbidity Endpoint Trials

0

10,000

20,000

30,000

40,000

50,000

60,000

Num

ber o

f pati

ents

44,264

51,878

19,335

12,565

1,405

1. Schrader et al. Stroke. 2005;36:1218–1226; 2. http://www.roadmapstudy.org/resident.aspx; 3. Parving et al. N Engl J Med. 2001;345:870–878; 4. Lewis et al. N Engl J Med. 2001;345:851–860; 5. Carson et al. J Card Fail. 2005;11:576–585; 6. Papademetriou et al. J Am Coll Cardiol. 2004;44:1175–1180; 7. www.atacand.com; 8. Brenner et al. N Engl J Med. 2001;345:861–869; 9. Pitt et al. Lancet. 2000;355:1582–1587; 10. Dickstein et al. Lancet. 2002;360:752–760; 11. Dahlof et al. Lancet. 2002;359:955–1003; 12. Cohn et al. N Engl J Med. 2001;345:1667–1675; 13. www.novartis.com; 14. Pfeffer et al. N Engl J Med. 2003;349:1893–1906; 15. Julius et al. Lancet. 2004;363:2022–2031; 15. www.ontarget-micardis.com.

6,4054,449

Val-HeFT12IRMA II3

LIFE11

ONTARGET®16

TRANSCEND®16

PRoFESS®16NAVIGATOR13

VALIANT14

VALUE15

OPTIMAAL10

ELITE II9

RENAAL8SCOPE6

CHARM7

MOSES1

IDNT4

I-Preserve5

ROADMAP2

Epro-sartan

Lo-sartan

Val-sartan

Cande-sartan

Irbe-sartan

Telmi-sartan

Olme-sartan

Telmisartan performs when needed most…

lets see how

Several studies conducted clearly exhibit that during early morning hours there

is a surge in BP.

This early morning surge is BP is directly linked with high occurrence of

CV incidents such as Stroke & MI during early morning hours

12 2 4 6 8 10 12 2 4 6 8 10 12

PM AM

Surge in Blood Pressure

Surge in CV Events such as MI and STROKE

With passing time, the Anti-Hypertensive effect of drug starts to wear off

ARBs other than Telmisartan

ARBs Other than Telmisartan

12 2 4 6 8 10 12 2 4 6 8 10 12

PM AM PM

Surge in Blood Pressure

Surge in CV Events such as MI and STROKE

24-Hour Plasma Half-life gives protection to Hypertensive Patients through-out the day, specially during early hours of the dayOver 30-Hour Plasma Half-life gives protection to Hypertensive Patients through-out the day, specially during early hours of the day

Superior BP Control and Protection

Telmisartan plus Amlodipine

TelmisartanAmlodipine

Provides protection to your patients during early hours of the day when cardiac events have high probability of occurrence

Telmisartan vs. Valsartan – last 6 hours

The MICADO-II Study

SBP DBP

-12

-10

-8

-6

-4

-2

0

Valsartan Telmisartan

BP co

mpa

red

with

the

initi

al v

alue

in la

st 6

hou

rs

befo

re re

peati

ng d

osin

g (m

mhg

)

* P = 0.02 versus Valsartan**P = 0.01 versus Valsartan

*

**

White et al Am J Hypertension 2004;17:347-353

Telmisartan vs. Valsartan – last 6 hours

Mallion et al. (1999)

DBP

-12

-10

-8

-6

-4

-2

0

Losartan Telmisartan

Dias

tolic

BP

com

pare

d w

ith in

itial

val

ue (m

mHg

)

P < 0.05 for Losartan

DBP

-12

-10

-8

-6

-4

-2

0

Ding et al. (2004)

Mallion et al. J Hum Hypertens 1999;13: 657-664Ding et al. Int J Clin Pract Suppl 2004;58 16-22

Telmisartan/Amlodipine vs. Valsartan / Amlodipine4 Weeks 8 Weeks 12 Weeks

-12

-10

-8

-6

-4

-2

0

Mea

n dr

op in

BP

from

Ba

selin

e (m

mH

g)

*SBPDBP

Replacement of Valsartan by Telmisartan reduced mean SBP and DBP by 7.1 and 6.5 mmHg at 4 weeks, 6.9 and 5 mmHg at 8 weeks, 10.5 and 7 mmHg at 12 weeks respectively. All patients were taking 5mg amlodipine

Oxi Med Cell Longev. (2010) 3(5): 342-346

Telmisartan Plus Amlodipine Has a Safety and Tolerability Profile Similar to Placebo

Se-ries1

0

2

4

6

8

10

12

0 0

4.3 4.3

0 0 0

2.2

10.9

0

1.30.9 0.9

0.6

1.91.3

2.2

1.3

6.0

7.8

1.1 1.1 1.1 1.11.4

1.82.2

3.0

4.7 4.8

Patie

nts w

ith

AEs >

1%

inci

denc

e (%

) A mono (n = 319) T/A (n = 789)Placebo (n = 46)

Littlejohn et al. J Clin Hypertens. 2009;11:207–213.

Fatigue Oedema Sinusitis Naso-pharyn-

gitis

Upper respiratory

tract infection

Influenza Back pain

Dizzi-ness

Headache Peripheral oedema

An Effective Anti-Hypertensive Combination Providing Holistic and Sustained BP Control

+Compared to other CCBs, Amlodipine has:- Longest Plasma Half lifeAM

LODI

PINE

Compared to other ARBs, Telmisartan has:- Longest Plasma Half life- Highest level of Distribution- Lowest Renal Excretion - Superior BP Control & Protection

TELM

ISAR

TAN