the role of lercanidipine in the treatment of hypertension: blood pressure control and beyond
DESCRIPTION
The role of lercanidipine in the treatment of hypertension: Blood pressure control and beyond Claudio Borghi Department of Internal Medicine, Aging and Kidney Diseases University of Bologna, Bologna Italy. Choice of Antihypertensive Drugs. - PowerPoint PPT PresentationTRANSCRIPT
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
0.5
1.0
1.5
2.0
Haza
rd r
ati
o f
or
card
iova
scu
lar
eve
nt
-90 -25 0 25 50 72
CV Endpoint
Albuminuria reduction (%)
0.0
0.5
1.0
1.5
2.0
Haza
rd r
ati
o f
or
heart
fail
ure
-90 -25 0 25 50 72
Heart Failure
De Zeeuw et al; Circulation 2004
Viviani GL et al, J Cardiovasc Pharmacol 2002
*p<0.05 vs B
*
*
**
*
*
*
*
**
*
*
*
*
**
*
*
* **
**
*
Systolic BP
Diastolic BP
Fasting blood glucose
HbA1
mm
Hg
mm
Hg
mg/
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.