Cardiovascular Risk in Hypertension – Can We Ask for More?

The burden of cardiovascular (CV) disease remains high nowadays, despite the tremendous development in the therapeutic strategies that has occurred during the last 30 years. The growing focus on pharmacological strategies capable of interacting with key pathophysiological mechanisms has resulted in a better control of CV disease. The renin-angiotensin system (RAS) is involved in many pathophysiological processes underlying the development of major CV and renal diseases and, thus, it represents an 'ideal' target for the pharmacological treatment of these clinical conditions. Recently, in addition to the traditional therapeutic approaches, mostly based on the use of ACE inhibitors and/or angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]), the scientific and medical community have focused on a new therapeutic possibility to interfere with RAS activity. Indeed, the first compound of the new drug class of direct renin inhibitors, aliskiren, has been made available for clinical use. The therapeutic properties of aliskiren are of particular interest, since it interferes with the enzymatic activities of renin, the key rate-limiting step of the RAS cascade. This unique mechanism of action, e.g. occupation of the renin active site, provides an 'upstream' modulation in the RAS enzymatic-proteic cascade. This results in an inhibition of the biological properties of renin to promote the cleavage of the angiotensin I peptide from the angiotensinogen substrate.Clinical studies have demonstrated that the use of aliskiren provides antihypertensive efficacy comparable with, or even superior to, that observed with other classes of antihypertensive drugs. Also, the addition of aliskiren to different antihypertensive strategies results in a further significant increase in blood pressure (BP) reduction than those achieved with monotherapy based on diuretics, calcium-channel antagonists, ACE inhibitors and ARBs. The overall safety and tolerability of aliskiren are comparable with other classes of antihypertensive drugs and almost overlap with placebo. Recent evidence also demonstrates that aliskiren is effective in promoting the regression of organ damage (e.g. microalbuminuria and left ventricular hypertrophy), beyond its BP-lowering properties and in addition to standard therapies, including ARBs. An ambitious programme of clinical development of this modern antihypertensive drug will investigate whether aliskiren may further limit the incidence of major CV and renal events in hypertensive patients with co-morbidities, treated with the available therapeutic strategies, including ACE inhibitors and ARBs.