Copyright © 2023 The Author(s): This is an open-access article distributed under the terms of the CC BY-NC 4.0 which permits unrestricted use, distribution, and reproduction in any medium for non-commercial use provided the original author and source are credited

Francesco Fici ^1,2 , Gokhan Faikoglu ³* , Guido Grassi ^4,5 , Nicolas Roberto Robles ^1,2,6 , Kubra Saygisever-Faikoglu ³

1. Catedra de Riesgo Cardiovascular, Universidad de Salamanca, Salamanca, Spain

3. Department of Pharmacology, Cerrahpasa Faculty of Medicine, Istanbul University, Cerrahpasa, Istanbul, Turkey

4. Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy

Article Info:

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Article History:

Received 03 Feb 2023

Reviewed 24 Feb 2023

Accepted 01 March 2023

Published 15 March 2023

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Cite this article as:

Fici F, Faikoglu G, Grassi G, Robles NR, Faikoglu KS,All About Lercanidipine: Ten Questions and Answers, Journal of Drug Delivery and Therapeutics. 2023; 13(3)P1-P3 DOI: http://dx.doi.org/10.22270/jddt.v13i3.5769 ____________________________________________________________________________________________________________

*Address for Correspondence:

Gokhan Faikoglu, Department of Pharmacology, Cerrahpasa Faculty of Medicine, Istanbul University, Cerrahpasa, Istanbul, Turkey

Dihydropyridine calcium channel blockers (DHP‑CCBs) are first–line drugs in antihypertensive therapy, either as monotherapy, or in combination with other antihypertensive drugs, as recommended by ESC/ESH ¹. Lercanidipine, a third-generation calcium channel blocker, is characterized by high vascular selectivity, high lipophilic properties, slow onset and long duration of pharmacological effect. Therefore, lercanidipine is different from a number of other CCBs ².

Dihydropyridine‑CCBs reversibly inhibit voltage-activated L-type Ca++ channels, located in the smooth muscle cells of the arteries ^3,4. The reduction of intracellular calcium level leads to vasodilation and consequently to blood pressure (BP) reduction. Differently from other dihydropyridine CCBs, lercanidipine inhibits both L and T calcium channels ⁵. There is evidence that T channels are particularly expressed in the renal efferent arterioles, while L channels are particularly located in the afferent arterioles ^6,7.

Therefore, lercanidipine blocking both L and T channels, dilates afferent and efferent renal arterioles and thereby prevents the increase of glomerular pressure. The result is a decrease of filtration fraction and, therefore, a kidney function protective effect ⁸.

Double-blind, randomized, comparative trials and large open, observational studies have shown that, lercanidipine (5-20mg once daily) significantly decreases systolic and diastolic blood pressure (SBP/DBP), assessed either as office and home measurement or as 24-hours monitoring (ABPM). Responder rate (SBP/DBP reduction greater than 20 and 10 mmHg respectively) is achieved by 62%-72% of patients ^9,10,11. The antihypertensive efficacy of lercanidipine has also been successfully reported in patients with isolated systolic hypertension, ^12,13, with diabetes, ¹⁴ and with cardiovascular disease ¹⁵. The therapeutic activity does not differ statistically from that of amlodipine, felodipine, nifedipine GITS, lacidipine, manidipine, ¹⁶, losartan ¹⁷ and candesartan ¹⁸.

Blood pressure reduction during lercanidipine treatment is sustained throughout 24-hour, with a significant reduction of morning BP rise and BP variability ^10,11,19,20.

4. Is the antihypertensive effect different according to the age and gender of patients?

The antihypertensive effect of lercanidipine is not different between young and elderly patients, as well between women and men ^{10, 21}.

5. What is the relationship between lercanidipine and endothelial dysfunction?

Essential hypertension is associated with impaired endothelium-mediated nitric oxide (NO) release, induced by oxidative stress. Therefore, the vascular tone shifts to vasoconstriction, resulting in higher peripheral vascular resistance ²². In patients with essential hypertension, lercanidipine significantly increases endothelium-mediated vasodilation, through the release of NO. Additionally the drug shows, antioxidant activity, lowering some markers of oxidative stress, as lipoperoxides, isoprostanes and malondialdehyde and asymmetric dimethylarginine ^20,23,24,25.

Lercanidipine significantly reduces the Augmentation index, as well the aortic SBP and pulse pressure ^13,20.

The increase in central aortic pressure is a marker of arterial stiffness and is involved in the development of cardiovascular events ^26,27,28. Lercanidipine, improving arterial stiffness and decreasing aortic pressure, shows a cardiovascular protective effect in hypertensive patients.

Differently from felodipine and nifedipine, chronic administration of lercanidipine, does not induce sympathetic activation, and does not increase plasma norepinephrine level. This aspect has an important clinical relevance considering that, in hypertensive patients, sympathetic overdrive is associated with tachycardia and development of cardiovascular events ^29,30.

Hypertension remains a major risk factor for kidney disease ³¹. Lercanidipine blocking both L and T channels, dilates afferent and efferent renal arteries, thus decreases intraglomerular pressure. The result shows that lercanidipine reduces chronic kidney disease progression ³². This is evident considering that lercanidipine lowers microalbuminuria in patients with type 2 diabetes similarly to ramipril, as reported in the DIAL study ³³. The improvement of renal function with was also obtained in patients with chronic renal failure ³⁴ and in subjects after renal artery intervention for atherosclerotic lesions ³⁵ in whom lercanidipine significantly increased glomerular filtration rate, after 6 months of treatment and decreased proteinuria.

Lercanidipine improving endothelial function and increasing NO bioavailability shows an atheroprotective effects. NO decreases oxidative stress, reduces vascular intimal and smooth muscle cell proliferation, decreases the plasma levels of E‑selectin, P‑selectin, adhesion molecules, inhibits cholesterol accumulation, LDL oxidation and platelet aggregation to the endothelium. Through these effects, lercanidipine decreases the risk of atherothrombotic events ^11,36,37. Moreover, in hypertensive patients lercanidipine treatment is associated with a regression of microvascular structural changes, evaluated as wall-to-lumen ratio ²⁰.

Lercanidipine is well tolerated, with a very low rate of adverse events, such as dizziness, headache, flushing, palpitations, and vertigo. ^{38, 39}. Particularly, compared with other CCBs (amlodipine, nifedipine, felodipine) lercanidipine, decreases ankle edema, by 56% ^{16 40}. Chronic treatment does not change laboratory parameters ^4,41 and is associated with very low (2.1%–<1%) withdrawal rate ^10,42.

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