Mineralocorticoid Receptor Antagonists in Cardiovascular Medicine: Looking for the Forest Among the Trees

Abstract

Mineralocorticoid receptor antagonists (MRAs) were initially introduced six decades ago, when spironolactone, a first generation nonselective MRA was developed [1]. MRAs were immediately placed at the epicenter of cardiovascular medicine, mainly, due to their blood pressure lowering effects. Thereafter, a great scientific effort lead to a thorough evaluation of such agents, resulting in a stable evolve of this category of drugs, as well as in vast clinical experience. Recently, MRAs emerged at the epicenter of scientific interest after the approval of finerone (a third generation, non-steroidal MRA), and the development of novel hypokalemic agents [2-6]. Nowadays, all the abovementioned scientific efforts have provided three generations of MRAs, along with a well-established benefit in several crucial cardiovascular comorbidities and life expectancy, featuring a quite useful option in the armamentarium of physicians in everyday clinical practice. More specific, MRAs are currently considered as a second-line drug for the management of arterial hypertension, while they portrait the most efficacious add-on therapy for the management of drug resistant arterial hypertension [7-9]. Moreover, MRAs are the gold-standard therapy in patients with bilateral primary aldosteronism [10]. Accumulating data suggests that both spironolactone and eplerenone result in amelioration of mortality outcomes in patients with heart failure with reduced ejection fraction, and left ventricular dysfunction after myocardial infarction [11-16]. Furthermore, MRAs are indicated for the management of albuminuria in concomitant administration with renin-angiotensin system blockers [17, 18]. Altogether, MRAs are ascertained as a fundamental class of drugs for the multifactorial management of patients with cardiovascular disease; however, their usage remains quite restricted. The point behind this fact lies in the potential life-threatening side effects of such agents, as hyperkalemia and acute kidney injury. In this end, the recently developed third generation, more selective, and non-steroidal MRAs seem to offer a substantial cardiorenal protection with a parallel promising safety in terms of the abovementioned side effects [19-27]. In the current special issue published by the Current Pharmaceutical Design, we sought to: A) highlight the pleiotropic effects of MRAs in the management of cardiovascular risk, b) critically discuss clinically meaningful aspects and to conclude in useful tips for everyday clinical practice, c) present novel perspectives with the introduction of more selective agents, such as the lately approved finerenone, d) discuss new perspectives about the safety of these agents with the use of new hypokalemic agents, e) suggest clinically meaningful implications for physicians, and f) underline the major aspects for further evaluation in the upcoming randomized controlled clinical trials. In this end, Professor Lovic and co-authors drafted a review article to thoroughly present the impact of mineralocorticoid receptors on the progression of cardiovascular disease, as well as the pathophysiological role of MRAs in the management of such deterioration [28]. Professor Faselis et al discussed about the effects of MRAs in the management of essential hypertension, while they innovatively present data on the use of MRAs in resistant hypertension compared with other second-line antihypertensive agents, and of major interest versus renal sympathetic denervation [29]. Professor Doumas and colleagues highlight the most important clinical aspects and future perspectives in the management of primary aldosteronism with such agents [30]. Prof Papademetriou and co-authors provide state of the art evidence and summarize future perspectives of the MRAs in the management of heart failure with reduced ejection fraction [31]. Likewise, Professor Tziomalos et al present data assessing the impact of these agents on heart failure with preserved ejection fraction [32]. Moreover, Professor Sarafidis and associates conducted a very useful review article on the role of MRAs in the treatment of chronic kidney disease and albuminuria, focusing on the new advantages by the development of the third-generation MRAs and novel hypokalemic agents [33]. Prof Manolis and colleagues conducted an interesting review on the MRAs side effects, providing significant guidance for the prevention and management of such events [34]. Professor Karagiannis et al innovatively present all the new perspectives on the potential wider use of MRAs, secondary tothe development of new hypokalemic agents; namely zirconium, and patiromer [35]. Last but not least, Professor Tsioufis and colleagues investigated the future perspectives with the ongoing evaluation of the third generation, non-steroidal MRAs, unveiling significant aspects that need to be further investigated in future randomized controlled trials [36]. © 2018, Bentham Science Publishers B.V.. All rights reserved.