The renin-angiotensin-aldosterone system (RAAS) is a major factor for the 
development and maintenance of hypertension and a major cause for cardiovascular 
remodeling and cardiovascular complications through its active peptide 
angiotensin (Ang) II. Blockade of RAAS with ACE inhibitors (ACEIs) results in 
suppression of Ang II levels, which eventually return to baseline levels after 
prolonged ACEI administration. This leads to an escape phenomenon through 
generation of Ang II from enzymes other than ACE and led to the hypothesis that 
dual blockade of RAAS with an ACEI/Ang receptor blocker (ARB) combination could 
lead to total blockade of RAAS, since ARBs block the action of Ang II at the AT1 
receptor level, irrespective of the mechanism of Ang II generation and will have 
an additive blood pressure (BP)-lowering effect. However, this hypothesis has 
not materialized clinically, as the ACEI/ARB combination produces modest BP 
reductions that are not significantly greater than monotherapy with the 
component drugs, and is frequently associated with higher incidence of side 
effects. A new dual RAAS blockade with the direct renin inhibitor aliskiren and 
the ARB valsartan produces greater BP reductions than monotherapy with the 
component drugs and is safe and well tolerated. The combination of aliskiren 
with valsartan, and with other antihypertensive drugs is discussed.