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

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.

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

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  1. The role of lercanidipine in the treatment of hypertension: Blood pressure control and beyond Claudio BorghiDepartment of Internal Medicine, Aging and Kidney DiseasesUniversity of Bologna, BolognaItaly

  2. 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

  3. 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

  4. SBP DBP HR (mmHg) (mmHg) (b/min) ns Changes vs. baseline p<0.001 P<0.001 Circo A. J Cardiovasc Pharmacol, 1997

  5. % patients (BP <140/90 mmHg) (BP decrease > 10%) Circo A, J Cardiovasc Pharmacol, 1997

  6. Office BP Home BP P<0.05 P<0.05 P<0.05 Blood pressure (mmHg) P<0.05 P<0.05 P<0.05 P<0.05 P<0.05 Ribstein J et al , J Hypertens 2002

  7. Blood pressure (mmHg) P<0.001 P<0.001 P<0.01 P<0.01 Barbagallo M et al, Aging Clin Exp Res, 2000

  8. Hemodynamic indices before and after 10- weeks of antihypertensive treatment in patients with ISH P<0.02 P<0.002 P<0.002 P<0.02 P<0.001 P<0.001 P<0.001 Mackenzie IS et al, Hypertension 2009

  9. 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

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

  11. P<0.05 Lercanidipine Ramipril P<0.05 Dalla Vestra M et al, Diab Nutr Metab, 2004

  12. RENAAL Study: 6-month reduction of proteinuria and cardiovascular outcome CV Endpoint Heart Failure 2.0 2.0 1.5 1.5 Hazard ratio for cardiovascular event 1.0 Hazard ratio for heart failure 1.0 0.5 0.5 0.0 0.0 -90 -25 0 25 50 72 -90 -25 0 25 50 72 Albuminuria reduction (%) Albuminuria reduction (%) De Zeeuw et al; Circulation 2004

  13. Systolic BP Fasting blood glucose * * * * * * mg/dL * mmHg * * * * * Diastolic BP HbA1 * * * * % mmHg * * * * * * * * *p<0.05 vs B Viviani GL et al, J Cardiovasc Pharmacol 2002

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

  15. % of patients with AE’s Barrios V et al, Blood Pressure 2002

  16. Blood pressure mmHg DBP SBP Lercanidipine 10-20 mg Nifedipine GITS 30-60 mg Felodipina 10-20 mg Treatment discontinuation for AE’s Leg edema % of patients P<0.05 % of patients P<0.05 P<0.05 Romito R et al, Am J Hypertens, 2003

  17. Primary end-point Ankle edema P<0.0001 P<0.001 P<0.001 P<0.0001 % patients withA.E.s % patients with A.E.s Headache Flushing P<0.001 P<0.001 % patients with A.E.s P<0.001 P<0.001 % patients with A.E.s Lercanidpine Borghi C et al, Blood Pressure, 2003

  18. 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 mightreduce 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.

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