The combination of simultaneous RAS blockade (AT1R) and RAS stimulation (AT2R) represents a novel promising therapeutic concept, which is distinct from previous attempts of double intervention in the RAS by dual blockade. The add-on of AT2R stimulation complements and augments the anti-inflammatory and anti-fibrotic effects of the AT1R blockade. This combined intervention may address the need for further risk reduction in patients with well-controlled blood pressure or where further blood pressure reduction is not desired, such as in patients with isolated systolic hypertension, with renal dysfunction or in the elderly.