Despite compelling evidence for the efficacy of primary prevention, cardiovascular disease (CVD) remains the main cause of mortality in EuropeCitation1. Arterial hypertension is one of the leading causes of death and disability worldwideCitation1, nevertheless evidence suggests that the control of blood pressure (BP) is still suboptimalCitation2. Hypertension, defined as sustained elevation of brachial blood pressure, is a major risk factor for cardiovascular disease, but to stratify CVD risk many other risk factors are considered. In hypertensive subjects, renal subclinical organ damage is associated with a 10 year risk of cardiovascular events of 20%. Baseline carotid intima–media thickness (IMT) has been shown to predict cardiovascular events independently of BP. Asymptomatic peripheral vascular diseases have prospectively been reported to be associated with an incidence of cardiovascular events approaching 20% over 10 yearsCitation3. In addition, pulse wave velocity (PWV) and central aortic pressure (CAP) are gaining importance as CV risk factors. Pulse wave velocity, a measure of vascular stiffness, has been related to cardiovascular riskCitation4 and hypertensive patient mortalityCitation5 in the elderly, in patients with end-stage renal disease, and in population-based analysesCitation6–8.
Further to life-style interventions, efforts should be made to find effective, safe and easy-to-use pharmacological strategies able to control BP and prevent organ damage, thus reducing CV risk. The 2013 ESH/ESC guidelinesCitation9 underline that, no matter which drug is used, monotherapy can effectively reduce BP in only a limited number of hypertensive patients; in turn, most patients will require the combination of at least two drugs to achieve BP control. ESH/ESC guidelines recommend taking into consideration the combination of two drugs as initial treatment whenever hypertensive patients have a high initial BP or are classified as being at high/very high cardiovascular risk because of the presence of organ damage, diabetes, renal disease, or a history of cardiovascular diseaseCitation9.
Several fixed-dose combinations of antihypertensive drugs are currently available, with overall similar efficacy in the reduction of BP. Therefore, the effects beyond the mere reduction of BP should be taken into account when selecting an anti-hypertensive treatmentCitation10.
The association of a calcium channel blocker (CCB) and a modulator of the renin–angiotensin system (RAS) appears an effective optionCitation9. Among different CCBs, lercanidipine, a third-generation CCB, has gained great attention given its peculiar pharmaceutical properties and its favorable efficacy/safety ratioCitation10. Lercanidipine has been reported to exert reno-protective effects and to improve lipid profile and glucose toleranceCitation10. A number of clinical trials have demonstrated the lercanidipine/enalapril combination to effectively reduce BP showing better efficacy and tolerability than monotherapy with either agent. The fixed-dose combination of lercanidipine and enalapril is particularly advantageous since it can exert the beneficial effects on macro- and micro-vascular structure, arterial distensibility, and oxidative stress of both CCB and RAS blockersCitation11,Citation12. These benefits do translate into favorable clinical outcomes in a number of conditions, e.g. renal diseaseCitation10. Both these kinds of drug appear to diminish CVD more than can be attributable to BP lowering alone. Based on this evidence, a fixed-dose combination of lercanidipine/enalapril may provide effective cardiovascular protection.
In this supplement, eight interesting papers report the results of independent investigations on lercanidipine/enalapril, aimed at elucidating the properties of these combination strategies including those that go beyond BP reduction.
In the first paper, Professor Gianfranco Parati discusses the vascular effects of the lercanidipine/enalapril combination, and comments on their potential clinical relevance. Then, Professor Damiano Rizzoni presents two meta-analyses, the former investigating the dose–response relationship of fixed-dose lercanidipine + enalapril and the latter evaluating the efficacy and safety of this combination in four large observational studies, conducted in unselected populations in a “field-practice” scenario.
In the fourth manuscript, Professor Tsioufis presents the results of a randomized trial comparing the effects of the lercanidipine/enalapril combination versus amlodipine/enalapril and hydrochlorothiazide/enalapril on blood pressure, target organ damage and sympathetic activation. Target organ damage, and in particular renal damage, is also the subject of the fifth paper on the RED LEVEL randomized trial by Professor Robles: this study directly compares the effect of the lercanidipine + enapril and the enalapril + amlodipine combinations on renal function and albuminuria in a hypertensive population.
Last, three major studies from China. Dr Peixiao describes the results of a randomized trial investigating the effects of lercanidipine on circulating endothelial progenitor cells (EPCs), an emerging marker of cardiovascular disease and hypertension, in elderly patients. Dr Peng then provides us with robust evidence on the efficacy of lercanidipine-based medical therapy and renal artery stent as treatment for renal artery stenosis. The last manuscript, by Dr. Xu, compares the effectiveness of lercanidipine and felodipine on day-to-day home blood pressure variability.
We believe that this supplement – second of a series focused on lercanidipine and published in this journal – adds important new evidence on the use of the lercanidipine/enalapril combination in hypertensive patients and will help physicians in tailoring interventions for the treatment of hypertension.
Transparency
Declaration of funding
Editorial assistance was supported by Recordati.
Declaration of financial/other relationships
E.A.R. has disclosed that he has no significant relationships with or financial interests in any commercial companies related to this study or article.
The CMRO peer reviewer on this editorial has no relevant financial or other relationships to disclose.
Acknowledgments
Editorial assistance for the preparation of this manuscript was provided by Luca Giacomelli PhD of Content Ed Net.
References
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- Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 2013;31:1281-357
- Burnier M. Renal protection with calcium antagonists: the role of lercanidipine. Curr Med Res Opin 2013;29:1727-35
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- Duda-Seiman D, Duda-Seiman C, Borcan F, et al. Calcium channel blockers – benefits upon vascular biology in hypertensive patients. Cardiovasc Hematol Agents Med Chem 2015;13:54-62