Since Fleckenstein’s pioneering studies about 35 years ago, calcium channel blockers have become a cornerstone in antihypertensive treatment, thanks to a large number of randomized controlled trials in which calcium blockers have been compared with placebo or no treatment. These trials showed that blood pressure lowering by these compounds can effectively reduce stroke, major cardiovascular events, and cardiovascular and all-cause death. A number of other controlled randomized trials have compared calcium channel blockers with other antihypertensive agents and have shown that, for similar blood pressure reductions, similar incidences of all types of cardiovascular fatal and nonfatal events were observed.
Almost all the randomized trials that have compared calcium channel blockers with placebo, and have thus provided the most solid evidence of the significant beneficial effects of these compounds in the prevention of cardiovascular disease, have used compounds belonging to the chemical class of dihydropyridines, which are possessed of a higher vascular selectivity and guarantee a marked reduction in systolic and diastolic blood pressure without adverse effects on myocardial contractility or in the smooth muscles of other body systems (such as the gastrointestinal tract).
The therapeutic use of calcium channel blockers in hypertension has achieved unanimous consensus particularly after the introduction of a subclass of compounds free of the rapid onset and short duration of action of early agents, and endowed of a prolonged and smooth type of activity. This subclass, often referred to as third-generation calcium channel blockers, is composed of highly lipophilic compounds whose long duration and slow onset of action are due to their strong binding to the lipid bilayer of the vascular smooth muscle cell membrane. Lercanidipine is the most widely used among compounds belonging to this interesting subclass of calcium channel blockers.
Although lercanidipine was initially developed, investigated and used in Europe, its clinical use has spread to other parts of the world, and this widespread clinical use has been accompanied by investigators’ interest in further testing lercanidipine clinical properties. The present journal issue collects five papers reporting studies carried out in China, Vietnam and Lebanon, illustrating the type of interest raised by lercanidipine in the medical context of these countries. Stroke is the most frequent cardiovascular complication of hypertension in the Far East, where increasing attention is directed to the use of calcium channel blockers because of some evidence that they may be particularly effective in stroke prevention, probably due to their antiatherosclerotic action and to a better and smoother blood pressure control. The paper by Cao Thuc Sinh et al. in this journal issue witnesses deep interest of Vietnam investigators in treatment of ischemic stroke, and the paper by Ying Wu et al., a collaborative study in a large number of Chinese hospitals, reflects the interest in blood pressure control and control of blood pressure variability indices such as the trough to peak and the smoothness index, by lercanidipine and other calcium channel blockers.
Lipophilic calcium channel blockers have often attracted the attention of investigators because of experimental and clinical studies suggesting they may have not only the well known blocking actions on L-type calcium channels explaining the blood pressure lowering effect, but also on other calcium channel types (T- and/or N-subtypes), present in the kidney and probably responsible for a more balanced effect of lipophilic compounds on afferent and efferent glomerular arterioles, and of an antiproteinuric effect. The paper by Meng Peng et al. illustrates current interest in further exploring these important properties of lercanidipine and companion compounds.
Finally, there is increasing awareness that, in clinical practice, satisfactory control of blood pressure in most hypertensive patients cannot be achieved without combination therapy. This is particularly important in these parts of the world where blood pressure control is far from being optimal. Association of a calcium channel blocker and an angiotensin converting enzyme inhibitor is a logical and widely used solution both for efficacy and tolerability reasons. A paper by Z. Yang et al. from China reports testing of the combination of separate pills of lercanidipine and perindopril, whereas the paper by Arnaut reports experience in Lebanon with a single pill fixed combination of lercanidipine and enalapril. Fixed combination of two drugs in a single pill is known to increase adherence to treatment, and full adherence to treatment together with blood pressure lowering effectiveness of drugs are equally important components of a successful treatment of hypertension.
The papers published in this journal issue, while they witness the spreading of the clinical usage of calcium channel blockers, and in particular of lercanidipine, to the Middle and Far East, are also a demonstration of the increasing amount of clinical research that is being developed nowadays in these countries. We can only be delighted with these new contributions and welcome our colleagues’ help in making control of hypertension easier and more widely achieved.
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Declaration of funding
Editorial support for this manuscript was funded by Recordati.
Declaration of financial/other relationships
A.Z. has disclosed he has received lecture fees from Recordati.
CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no financial or other relationships to disclose.
Acknowledgments
Editorial assistance was provided by Luca Giacomelli PhD of Content Ed Net.