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

Lercanidipine and HBP Favorable pharmacological profile

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

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

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

% 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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 10-20 mg Nifedipine GITS 30-60 mg Felodipina 10-20 mg mmHg Romito R et al, Am J Hypertens, 2003

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

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.