TREATMENT OF ESSENTIAL HYPERTENSION WITH CALCIUM CHANNEL BLOCKERS: WHAT IS THE PLACE OF LERCANIDIPINE

In all actual clinical guidelines, dihydropyridine calcium channel blockers (CCBs) belong to the recommended first line antihypertensive drugs to treat essential hypertension. Several recent large clinical trials have confirmed their efficacy not only in lowering blood pressure but also in reducing cardiovascular morbidity and mortality in hypertensive patients with a normal or high cardiovascular risk profile. In clinical trials such as ALLHAT, VALUE or ASCOT, an amlodipine-based therapy was at least as effective, when not slightly superior, in lowering blood pressure and sometimes more effective in preventing target organ damages than blood pressure lowering strategies based on the use of diuretics, beta-blockers and blockers of the renin-angiotensin system. One of the main clinical side effects of the first and second generation CCBs including amlodipine is the development of peripheral edema. The incidence of leg edema can be markedly reduced by combining the CCB with a blocker of the renin-angiotensin system. This strategy has now led to the development of several fixed-dose combinations of amlodipine and angiotensin II receptor antagonists. Another alternative to lower the incidence of edema is to use CCBs of the third generation such as lercanidipine. Indeed, although no major clinical trials have been conducted with this compound, clinical studies have shown that lercanidipine and amlodipine have a comparable antihypertensive efficacy but with significantly less peripheral edema in patients receiving lercanidipine. In some countries, lercanidipine is now available in a single-pill association with an ACE inhibitor thereby further improving its efficacy and tolerability profile.

Essential arterial hypertension, therapy, dihydropyridine calcium channel blockers, hypertension, singlepill fixed-dose combinations

1. The ALLHAT officers and coordinators for the ALLHAT collaborative research group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the antihypertensive and lipid lowering treatment to prevent heart attack trial (ALLHAT). JAMA 2002;288:2981—97.

2. Julius S, Kjeldsen SE, Weber M, el al. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet 2004;363:2022—31.

3. Dahlöf B, Severs PS. Poulter NR, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding bendroflumethiazide, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lovering arm (ASCOT-BPLA): a multicentre randomized controlled trial. Lancet 2005;366(9489):895—906.

4. Jamerson K, Weber MA, Bakris GL, et al: for the ACCOMPLICH trial Investigators. Benazepril plus amlodipine or hydrochlorotiazide for hypertension in high risk patients. N Eng J Med 2008;359:2417— 28.

5. Abernethy DR, Schwartz JB. Calcium-antagonist drugs. N Eng J Med 1999;341:1447—57.

6. Herbette LG, Vecchiarelli M, Sartani A, Leonardi A. Lercadipine: short plasma half-life, long duration of action and high cholesterol tolerance its pharmacokinetic properties. Blood Press Suppl 1998;2:10—17.

7. Bang LM, Chapman TM, Goa KL. Lercanidipine: a review of its efficacy in the management of hypertension. Drugs2003;63:2449— 72.

8. Sironi G, Montagna E, Greto L, et al. Haemodynamic effects of lercanidipine in anaesthetized open-chest dogs. Arzneimittelforschung 1996;46:256—61.

9. Cherubini A, Fabris F, Ferrari E, et al. Comparative effects of lercanidipine, lacidipine and nifedipine gastrointestinal therapeutic system on blood pressure and heart rate in elderly hypertensive patients: the ELderly and LErcanidipine (ELLE) study. Arch Gerontol Geriatr 2003;37:203—12.

10. Romito R, Pansini MI, Perticone F, et al. Comparative effect of lercanidipine, felodipine, and nifedipine GITS on blood pressure and heart rate in patients with mild to moderate arterial hypertension: the Lercanidipine in Adults (LEAD) Study. J Clin Hypertens 2003;5:249—53.

11. Leonetti G, Magnani B, Pessina AC, et al.; COHORT Study Group. Tolerability of long-term treatment with lercanidipine versus amlodipine and lacidipine in elderly hypertensives. Am J Hypertens 2002;15:932—40.

12. Barrios V, Navarro A, Esteras A, et al. Antihypertensive efficacy and tolerability of lercanidipine in daily clinical practice. The ELYPSE study. Blood Press 2002;11:95—100.

13. Burnier M, Gasser UE. Efficacy and tolerability of lercanidipine in patients with hypertension: results of a Phase IV study in general practice. Expert Opin Pharmacother 2007;8(14):2215— 23.

14. Barrios V, Escobar C, de la Figuera M, et al. Tolerability of high doses of lercanidipine versus high doses of other dihydropyridines in daily clinical practice: the TOLERANCE study. Cardiovasc Ther 2008;26:2—9.

15. Barrios V, Escobar C, Navarro A, et al: LAURA Investigators. Lercanidipine is an effective and well tolerated antihypertensive drug regardless the cardiovascular risk profile: The LAURA study. Int J Clin Pract 2006;60(11):1364—70.

16. Borghi C. Lercanidipine in hypertension. Vasc Health Risk Manag 2005;1(3):173—82.

17. Dalla Vestra M, Pozza G, Mosca A, et al. Effect of lercanidipine compared with ramipril on albumin excretion rate in hypertensive type 2 diabetic patients with microalbuminuria: DIAL study. Diabetes Nutr Metab 2004;17:259—66.

18. Sasaki T, Maruyama H, Kase Y, et al. Antianginal effects of lercanidipine on the vasopressin or metacholine induced anginal models in rats. Biol Pharm Bull 2005;28(5):811—6.

19. Acanfora D, Gheorghiade M, Trojano L, et al. A randomized, double-blind comparison of lercanidipine 10 and 20mg in patients with stable effort angina: clinical evaluation of cardiac function by ambulatory ventricular scintigraphic monitoring. Am J Ther 2004;11(6):423—32.

20. Borghi C, Prandin MG, Dormi A, Ambrosioni E. Study group of the regional Unit of the Italian Society of Hypertension. Improved tolerability of the dihydropyridine calcium-channel antagonist lercanidipine: the lercanidipine challenge trial. Blood Press 2003;(Suppl 1): 14—21.

21. Lund-Johansen P, Stranden E, Helberg S, et al. Quantification of leg oedema in postmenopausal hypertensive patients treated with lercanidipine or amlodipine. J Hypertens 2003;21:1003—10.

22. Fogari R, Malamani GD, Zoppi A, et al. Comparative effect of lercanidipine and nifedipine Gastrointestinal Therapeutic System on ankle volume and subcutaneous interstitial pressure in hypertensive patients: a double-blind, randomized, parallel-group study. Curr Ther Res Clin Exp 2000;61:850—62.

23. Fogari R, Mugellini A, Zoppi A, et al. Differential effects of lercanidipine and nifedipine GITS on plasma norepinephrine in chronic treatment of hypertension. Am J Hypertens 2003;16:1357— 69.

24. Pedrinelli R, Dell’Omo G, Nuti M, et al. Heterogeneous effect of calcium antagonists on leg oedema: a comparison of amlodipine versus lercanidipine in hypertensive patients. J Hypertens 2003;21(10):1969—73.

25. Hollenberg NK. Observations on the safety of lercanidipine: adverse events from placebo-controlled trials. Am J Hypertens 2002;15:58A-9A.

26. Burnier M, Brown RE, Ong SH, et a]. Issues in blood pressure control and the potential role of single-pill combination therapies. Int J Clin Pract 2009;63(5):790—8.

27. Quan A, Chavanu K, Merkel J. A review of the efficacy of fixeddose combinations of olmesartan medoxomil/hydrochlorothiazide and amlodipine belatel/benazepril in factorial design studies. Am J Cardiovasc Drugs 2006;6:103—13.

28. Stergiou G, Makris T, Papavasiliou M, et al. Comparison of antihypertensive effects of an angiotensin-converting enzyme inhibitor, a calcium antagonist and a diuretic in patients with hypertension not controlled by angiotensin receptor blocking monotherapy. Hypertens 2005;23:883—9.

29. Fogari R, Zoppi A, Derosa G, et a]. Effect of valsartan addition to amlodipine on ankle oedema and subcutaneous tissue pressure in hypertensive patients. J Hum Hypertens 2007;21:220—4.

30. Cleophas TJ, van Ouwekerk BM, van der Meulen J, et al. Diabetics with hypertension not controlled with ACE-inhibitors: alternate therapies. Angiology 200 1;52(7):469—75.

31. Grandi AM, Solbiati F, Laurita E, et al. Effects of dual blockade of renin-angiotensin system on concentric left ventricular hypertrophy in essential hypertension: a randomized, controlled pilot study. Am J Hypertens 2008;21(2):231—7.

32. Agrawal R, Marx A, Haller H. Efficacy and safety of lercanidipine versus hydrochlorothiazide as add-on to enalapril in diabetic populations with uncontrolled hypertension. J Hypertens 2006;24(1): 185—92.

33. Hair PI, Scott LJ, Perry CM. Fixed-dose combination lercanidipinelenalapril. Drugs 2007;67(1):95—106.

34. Puig JG, Calvo C, Luurila 0, et al. Lercanidipine, enalapril and their combination in the treatment of elderly hypertensive patients: placebo-controlled, randomized, crossover study with four ABPM. J Hum Hypertens 2007;21(12):917—24.

35. Robles NR, Ocon J, Gomez CF, et al. Lercanidipine in patients with chronic renal failure: the ZAFRA study. Ren Fail2005:1:73—80.