While inhibition of the RAAS remains a fundamental and non-substitutable component in the management of hypertension and heart failure, largely owing to its well-documented antiproliferative and anti-inflammatory properties, the PRECISION trial data suggest that targeting an alternative pathway, compared to the standard treatment, such as the ET-1 pathway, may be more beneficial than merely combining classical antihypertensive drugs in patients with resistant HT [25,30]. Here, EDN1 is linked to heart failure.