The role of lercanidipine in the treatment of hypertension: Blood pressure control and beyond

Claudio BorghiDepartment of Internal Medicine, Aging and Kidney Diseases

University of Bologna, BolognaItaly

Choice of Antihypertensive Drugs

Five major classes of antihypertensive agents are considered suitable for the initiation and maintenance of antihypertensive treatment, alone or in combination. Thiazide diuretics, Calcium antagonists, ACE inhibitors, Angiotensin receptor antagonists β- blockers

ESH-ESC Guidelines J Hypertens 2007;25:1105-1187Reappraisal of EU Guidelines, J Hypertens 2009

Elevated lipophilicity (15 times vs. amlodipine)

High affinity for vascular membrane- Short plasma half-life Prolonged tissue half-life

High selectivity for vascular tissue- Lack of negative inotropic effect

- Increased vascular protection

Pharmacokinetic properties not affected by ageDouble route of excretion (renal and hepatic)No major drug-to-drug interaction

Circo A. J Cardiovasc Pharmacol, 1997

P<0.001

Chan

ges

vs. b

asel

ine

p<0.001

ns

SBP DBP HR(mmHg) (mmHg) (b/min)

Circo A, J Cardiovasc Pharmacol, 1997

(BP <140/90 mmHg) (BP decrease > 10%)

% p

atien

ts

Ribstein J et al , J Hypertens 2002

P<0.05

P<0.05

P<0.05

P<0.05

P<0.05

P<0.05

P<0.05

P<0.05

Office BP Home BP

Bloo

d pr

essu

re (m

mH

g)

Barbagallo M et al, Aging Clin Exp Res, 2000

P<0.001 P<0.001

P<0.01 P<0.01

Bloo

d pr

essu

re (m

mH

g)

Hemodynamic indices before and after 10- weeks of antihypertensive treatment in patients with ISH

P<0.001

P<0.001

P<0.001

P<0.002 P<0.002 P<0.02

P<0.02

Mackenzie IS et al, Hypertension 2009

• Regression of LVH (vs. Losartan) - Fogari R et al, J Hypertens 2000

• Improvement of endothelium - dependent vasodilatation- Taddei S et al, Hypertension 2003

• Balanced effects on renal vasculature- Sabatini M et al, Hypertension 2000

• Preservation of impaired renal function - Robles NR et al, Ren Fail 2005

Antioxidant effect of Lercanidipine, NO restoration and endothelial function in hypertensive patient.

LERCANIDIPINE

+

Taddei S et al Hypertension 2005

Dalla Vestra M et al, Diab Nutr Metab, 2004

P<0.05

P<0.05

Lercanidipine

Ramipril

RENAAL Study: 6-month reduction of proteinuria and cardiovascular outcome

Albuminuria reduction (%)

0.0

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2.0

Haza

rd r

ati

o f

or

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iova

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lar

eve

nt

-90 -25 0 25 50 72

CV Endpoint

Albuminuria reduction (%)

0.0

0.5

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1.5

2.0

Haza

rd r

ati

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or

heart

fail

ure

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Heart Failure

De Zeeuw et al; Circulation 2004

Viviani GL et al, J Cardiovasc Pharmacol 2002

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Systolic BP

Diastolic BP

Fasting blood glucose

HbA1

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Hg

mm

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dL%

Mechanism of interaction between BK, AT-II, NO and glucose transport

Henriksen EJ & Jacob S, J Cell Physiol 2003

Lercanidipine

.

.

% o

f pati

ents

with

AE’

s

Barrios V et al, Blood Pressure 2002

Drug Study % AE’s

Nifedipine GITS INSIGHT 49.0%

Amlodipine VALUE 39.2%

Romito R et al, Am J Hypertens, 2003

P<0.05

Treatment discontinuation for AE’s

Blood pressure

DBP SBP

Leg edema

P<0.05 P<0.05

% o

f pati

ents

Lercanidipine 10-20 mg Nifedipine GITS 30-60 mg Felodipina 10-20 mgm

mH

g

% o

f pati

ents

% p

atien

ts w

ith A

.E.s

P<0.001

P<0.001%

pati

ents

with

A.E

.s

P<0.001P<0.001

% p

atien

ts w

ith A

.E.s

P<0.001

P<0.001

Ankle edema

Headache Flushing

% p

atien

ts w

ithA.

E.s

P<0.0001

P<0.0001Primary end-point

Borghi C et al, Blood Pressure, 2003

Lercanidpine

ConclusionsConclusions DHP-CCB’s play a primary role in the treatment of HBP by reducing elevated BP values and the rate of major CV events.

Lercanidipine is highly effective in reducing BP both in the general population and in subgroups of high risk patients (elderly, ISH, diabetic, etc.) The treatment with Lercanidipine is associated with an extensive target organ and metabolic protection in addition and beyond BP control. Its peculiar tolerability profile vs. other compounds of the same class, is an additional key feature that increases the clinical effectiveness of antihypertensive treatment and might reduce the costs of HBP. All these features may largely justify a primary role for lercanidipine for the management of the global cardiovascular risk in a large proportion of patients with HBP.