1. 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

3. 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:
Reappraisal of EU Guidelines, J Hypertens 2009

4. Lercanidipine and HBP
Favorable pharmacological profile

5. Pharmacological profile of lercanidipine
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 age
Double route of excretion (renal and hepatic)
No major drug-to-drug interaction

6. DHP-CCB’s in HBP: lercanidipine
Favorable pharmacological profile
Effective blood pressure control

7. BP and HR in response to different doses of Lercanidipine in patients with mild-to-moderate HBP
SBP DBP HR
(mmHg) (mmHg) (b/min) ns
Changes vs. baseline
p<0.001
P<0.001
Circo A. J Cardiovasc Pharmacol, 1997

8. % of hypertensive patients normalized or responders to 4-week monotherapy with different doses of Lercanidipine
(BP <140/90 mmHg) (BP decrease > 10%)
% patients
Circo A, J Cardiovasc Pharmacol, 1997

9. Antihypertensive efficacy of Lercanidipine (10-20 mg/day) in elderly HBP patients. The AGATE study
Office BP Home BP
P<0.05
P<0.05
Blood pressure (mmHg)
P<0.05
P<0.05
P<0.05
P<0.05
P<0.05
P<0.05
Ribstein J et al , J Hypertens 2002

10. Effects of Lercanidipine in elderly patients with ISH
Blood pressure (mmHg)
P<0.001
P<0.001
P<0.01
P<0.01
Barbagallo M et al, Aging Clin Exp Res, 2000

11. Hemodynamic indices before and after 10- weeks of antihypertensive treatment in patients with ISH
Mackenzie IS et al, Hypertension 2009

12. DHP-CCB’s in HBP: lercanidipine
Favorable pharmacological profile
Effective blood pressure control
Extensive prevention/regression of TOD

13. Lercanidipine and TOD in hypertension
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

14. Antioxidant effect of Lercanidipine, NO restoration and endothelial function in hypertensive patient. +
LERCANIDIPINE
Taddei S et al Hypertension 2005

16. Albumin excretion rate in hypertensive diabetic patients treated with lercanidipine or ramipril.
Dalla Vestra M et al, Diab Nutr Metab, 2004

17. RENAAL Study: 6-month reduction of proteinuria and cardiovascular outcome
Albuminuria reduction (%)
0.0
0.5
1.0
1.5
2.0
Hazard ratio for cardiovascular event
-90
-25 25 50 72
CV Endpoint
Hazard ratio for heart failure
Heart Failure
De Zeeuw et al; Circulation 2004

18. DHP-CCB’s in HBP: lercanidipine
Favorable pharmacological profile
Effective blood pressure control
Extensive prevention/regression of TOD
Improvement of the metabolic profile

19. Effects of Lercanidipine on blood pressure and glycemic profile in patients with HBP and type-2 diabetes *
Systolic BP
Diastolic BP
Fasting blood glucose
HbA1
mmHg
mg/dL %
*p<0.05 vs B
Viviani GL et al, J Cardiovasc Pharmacol 2002

20. Mechanism of interaction between BK, AT-II, NO and glucose transport
Lercanidipine . .
Henriksen EJ & Jacob S, J Cell Physiol 2003

21. DHP-CCB’s in HBP: lercanidipine
Favorable pharmacological profile
Effective blood pressure control
Extensive prevention/regression TOD
Improvement of the metabolic profile
Favorable tolerabilty profile

22. Proportion of patients with AE’s after 3 months of treatment with lercanidipine in a population of 9059 patients. The ELYPSE trial
Drug
Study
% AE’s
Nifedipine GITS
INSIGHT
49.0%
Amlodipine
VALUE
39.2%
% of patients with AE’s
Barrios V et al, Blood Pressure 2002

24. Treatment discontinuation for AE’s
Safety and tolerability profile of different CCB’s in 325 adults (35-74 ys) hypertensive patients: the LEAD study (Randomized, double-blind study)
P<0.05
Treatment discontinuation for AE’s
Blood pressure
DBP SBP
Leg edema
% of patients
Lercanidipine mg
Nifedipine GITS mg
Felodipina mg
mmHg
Romito R et al, Am J Hypertens, 2003

25. Prevalence of drug-specific AE’s in the Lercanidipine Challenge Trial
% patients with A.E.s
P<0.001
Ankle edema
Headache
Flushing
% patients withA.E.s
P<0.0001
Primary end-point
Lercanidpine
Borghi C et al, Blood Pressure, 2003

26. Conclusions
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.