New developments in the pharmacological treatment of hypertension: dead-end or a glimmer at the horizon?

Abstract

Arterial hypertension is the most prevalent controllable disease world-wide. Yet, we still need to further improve blood pressure control, deal with resistant hypertension, and we hope to reduce risk "beyond blood pressure." The number of candidate molecules aspiring for these aims is constantly declining. The new possible approaches to combat high blood pressure include neprilysin/neutral endopeptidase (NEP) inhibition, particularly when combined with an angiotensin receptor blockade (such as the ARNI, LCZ696), phosphodiesterase 5 (PDE5) inhibition (KD027/Slx-2101), natriuretic agents (PL3994), or a long-lasting vasointestinal peptide (VIP) analogue (PB1046). Other options exploit the protective arm of the renin-angiotensin-aldosterone system by stimulating the angiotensin AT2 receptor (compound 21), the Mas receptor (AVE-0991), or the angiotensin converting enzyme 2. Finally, we review the possibilities how to optimize the use of the available treatment options by using drug combinations or by tailoring therapy to each patient's angiotensin peptide profile.

Fig. 1

Recent development of fixed-dose combinations. Schematic representation adapting the combination hexagon from guidelines for the management of arterial hypertension [1] by including direct renin inhibitors (and omitting α-blockers). Red lines demonstrate combinations recently approved (since 2011) or in clinical phase of development in addition to the previously established combinations (blue thick lines). Aliskiren + valsartan combination was discontinued (red double-crossed line). Patterned triangles demonstrate approved triple therapies. ARB angiotensin (AT1) receptor blocker, ACE angiotensin converting enzyme, CCB calcium channel blocker