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Levamlodipine BesylateLevamlodipine Besylate

New CCB half dose, save efficiency and safNew CCB half dose, save efficiency and safetyety

Dayi Hu, Dayi Hu, MD, FACC, FHRS, FESCMD, FACC, FHRS, FESC

Medical school of Tongji University, Shanghai PeoMedical school of Tongji University, Shanghai People’s Hospital of Peking University,Beijingple’s Hospital of Peking University,Beijing

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AmlodipineAmlodipine

A typical modern long acting CaA typical modern long acting Ca2+2+ channel blo channel blocker with significant antihypertensive effect.cker with significant antihypertensive effect.

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The antihypertensive effect in different age groupsThe antihypertensive effect in different age groups

Reduction in systolic BP

-30

-25

-20

-15

-10

-5

0

mm

Hg

mmHg -17.5 -23.9 -24.3

Young Middle-aged The elder

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Significant antihypertensive effectSignificant antihypertensive effect

*P<0.001

The systolic pressure change in mild and moderatehypertensive patients after administration of drugs

-35

-30

-25

-20

-15

-10

-5

0

mm

Hg

mmHg -33 -24

Amlodipine HCTZ

5

Outstanding antihypertensive effectOutstanding antihypertensive effect

Amlodipine vs. LasartanAmlodipine vs. Lasartan

P<0.001

Reduction in systolic BP

-20

-18

-16

-14

-12

-10

-8

-6

-4

-2

0

mm

Hg

mmHg -19 -13

Amlodipine Lasartan

n=97

n=93

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Significant antihypertensive effectSignificant antihypertensive effect

Amlodipine vs. ACEI , ARB (The Aged Hypertension)Amlodipine vs. ACEI , ARB (The Aged Hypertension)

Reduction in systolic BP

-30

-25

-20

-15

-10

-5

0

mm

Hg

-27 -16 -19

Amlodipine ACEI ARB

Amlodipine vs. ACEI, P=0.008 Amlodipine vs. ARB, P=NS

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The major heart terminals

Incidence of heart disease

Death of heart diseases

All myocardial infarction

All congestive heart failure

All cerebral apoplexy

Death caused by all the reasons

New onset diabetes

0.5 1 2

VALUE Study:

Julius S et al. Lancet. June 2004;363.

Valsartan / Amlodipine

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Amlodipine is remarkably superior in reducing the rate of cerebral Amlodipine is remarkably superior in reducing the rate of cerebral

apoplexy compared to other antihypertensive drugsapoplexy compared to other antihypertensive drugs

4040%%

1818%%1616%%

1414%%

P=0.038

P=0.004P=0.032

P=0.002

VS.VS.PlaceboPlacebo VS.VS.ACEIACEI VS.VS.ARBARB VS. VS. Diuretic /Diuretic /ββ-Blocker-Blocker

PREVENT(n=825)/CAMELOT(n=1318)/IDNT(n=1136PREVENT(n=825)/CAMELOT(n=1318)/IDNT(n=1136))Decr

ease

of t

he ri

sk o

f occ

urre

nce

Decr

ease

of t

he ri

sk o

f occ

urre

nce

of c

ereb

ral a

popl

exy(

%)

of c

ereb

ral a

popl

exy(

%)

ALLHAT(n=18102)/CAMELOT(n=1336)

IDNT(n=1146)/VALUE(n=15245IDNT(n=1146)/VALUE(n=15245))

ALLHAT(n=24309)/ASCOTALLHAT(n=24309)/ASCOT

(n=19257)(n=19257)

Franz H. Messerli et al. Hypertension. 2006;48:359-361.

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Amlodipine can effectively control early morning BP increaseAmlodipine can effectively control early morning BP increase

Its consistent 24 hour antihypertension effectIts consistent 24 hour antihypertension effect

It’s superior than other CCB in decreasing the rate of early morning BP increase.It’s superior than other CCB in decreasing the rate of early morning BP increase.

C. Macchiarulo et al. Cur Ther Res Clin Exp. 2001;62:236-253.

Before treatmentBefore treatment

2

3

4

5

6

7

8

9

10

Nifedipine60mg QD

N=20

Amlodipine10mg QD

N=20

Felodipine10mg QD

N=15

mm

Hg/H

mm

Hg/H

* P<0.05* P<0.05

**

**

SBPSBP DBPDBP

Nifedipine60mg QD

N=20

Amlodipine10mg QD

N=20

Felodipine10mg QD

N=15

The speed of early morning BP increase before and after treatmentThe speed of early morning BP increase before and after treatment

After treatmentAfter treatment

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Levamlodipine (Shi Hui Da) Levamlodipine (Shi Hui Da)

Amlodipine is a racemic compound composed of levorotary Amlodipine is a racemic compound composed of levorotary and dextrorotary forms. and dextrorotary forms.

The CaThe Ca2+2+ antagonist activity of levorotary form is approxim- antagonist activity of levorotary form is approxim-ately 1,000 times of the one of dextrorotary form and twice ately 1,000 times of the one of dextrorotary form and twice of the one of racemic compound..of the one of racemic compound..

Levamlodipine: half dose --the same effect of racemic amloLevamlodipine: half dose --the same effect of racemic amlodipine. Less side effects. dipine. Less side effects.

—— —— The New Generation Products of AmlodipineThe New Generation Products of Amlodipine

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Levamlodipine besylateLevamlodipine besylate (Shi Hui Da(Shi Hui Da))

Similar effectiveness in antihypertension?Similar effectiveness in antihypertension?

Safer?Safer?

Equal organ protection effect?Equal organ protection effect?

Amlodipine besylateAmlodipine besylate(Norvasc(Norvasc))

V.S.

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One of the Clinical Studies: Levamlodipine vs Amlodipine One of the Clinical Studies: Levamlodipine vs Amlodipine

Chinese Journal of Medicine, 2002,37(5);46-47

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Multi-center clinical study

The People’s Hospital of Beijing University (Hu Dayi, PI)The People’s Hospital of Beijing University (Hu Dayi, PI)

Capital Medical University Affiliated Beijing Tongren HospitalCapital Medical University Affiliated Beijing Tongren Hospital

Capital Medical University Affiliated Beijing Youyi HospitalCapital Medical University Affiliated Beijing Youyi Hospital

Capital Medical University Affiliated Beijing Xuanwu HospitalCapital Medical University Affiliated Beijing Xuanwu Hospital

Sino-Japan Friendship HospitalSino-Japan Friendship Hospital

Armed Police Contingent Hospital of BeijingArmed Police Contingent Hospital of Beijing

The No. 3 Hospital of Beijing UniversityThe No. 3 Hospital of Beijing University

Beijing HospitalBeijing Hospital

Capital Medical University Affiliated Beijing Fuxing HospitalCapital Medical University Affiliated Beijing Fuxing Hospital

Beijing Willow Hospital Beijing Willow Hospital

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The trough / peak value of The trough / peak value of levamlodipine besylate (Shi Hui Da) levamlodipine besylate (Shi Hui Da)

85% 83%

0%

20%

40%

60%

80%

100%

SBP DBP

T/P

(%)

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The changes of BP before treatment, after treatment and during drug holidays

Before Before TreatmentTreatment

Eight weeks Eight weeks treatmenttreatment

Drug holiday 1 Drug holiday 1 for 24hfor 24h

Drug holiday 2 Drug holiday 2 for 48hfor 48h

SBPSBPLevamlodipineLevamlodipine 141.3141.312.912.9 131.5 131.5 10.110.1** 135.3 135.3 11.511.5## 136.4 136.4 11.211.2##

AmlodipineAmlodipine 141.2 141.2 12.712.7 133.9 133.9 11.011.0** 136.9 136.9 11.511.5## 138.0 138.0 11.311.3##

DBPDBPLevamlodipineLevamlodipine 91.5 91.5 7.27.2 84.6 84.6 7.97.9** 85.8 85.8 7.67.6## 87.4 87.4 8.28.2##

AmlodipineAmlodipine 89.6 89.6 6.36.3 85.5 85.5 6.96.9** 86.8 86.8 6.96.9## 87.8 87.8 7.47.4##

CBP, n=80

*p<0.05: The value of SBP and DBP at the end of 8 weeks’ treatment compared with those of no drug administered.#p>0.05: The value of SBP and DBP after not administered for 24h or 48h compared with those at the end of 8 weeks’ treatment.

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The reduction of SBP and DBP after eight weeks The reduction of SBP and DBP after eight weeks treatment in the two groupstreatment in the two groups

-12.64

-15.82

-10.86-13.58

-20

-15

-10

-5

0

SBP DBP

Levamlodipine Amlodipine

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The SBP and DBP ChangesThe SBP and DBP Changesduring drug holiday 1 after eight weeks treatment during drug holiday 1 after eight weeks treatment

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The SBP and DBP Changes during drug holiday 2 after The SBP and DBP Changes during drug holiday 2 after eight weeks treatmenteight weeks treatment

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Adverse Events Adverse Events (eight weeks treatment )(eight weeks treatment )

0

0.5

1

1.5

2

2.5

3

3.5

4

Headache Light Headed Heart

Palpitation

Ankle Swollen Blushed face Upset Stomach

%

Levamlodipine Amlodipine

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Conclusion

Both 2.5mg Levamlodipine besylate and 5mg Amlodipine Both 2.5mg Levamlodipine besylate and 5mg Amlodipine besylate reduce BP effectively. besylate reduce BP effectively.

The incidence of Levamlodipine adverse effects is low.The incidence of Levamlodipine adverse effects is low.

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ConclusionConclusion

CCB is the most common antihypertensive drug used CCB is the most common antihypertensive drug used in Chinese hypertensives. in Chinese hypertensives.

Levamlodipine besylate (Shi Hui Da) is both save and Levamlodipine besylate (Shi Hui Da) is both save and effective.effective.

Half dosage, Same effect and safety.Half dosage, Same effect and safety.

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ThanksThanks！！