The dual blockade of the renin-angiotensin system in Internal Medicine: after ONTARGET trial

BACKGROUND In the increasing progress of scientific knowledge, every new discovery is a basis for new problems. In fact, after the success of Angiotensin-Converting Enzyme (ACE)-inhibitors in different cardiovascular diseases, the evidence of the “escape” of ACE and the discovery of Angiotensin- Receptor Blockers (ARBs) became the basis for a new question: is a dual blockade of the Renin-Angiotensin System (RAS) correct? DISCUSSION The different trials carried out (also the latest ONTARGET) didn’t give reliable answers, because differences were found both in the various diseases (hypertension, heart failure, coronary disease, nephropathy, diabetic or not), and between the single drugs of the class. We can say that this combination treatment didn’t show reliable clinical efficacy yet, except in heart failure and in some subgroups of hypertensive patients, checking carefully serum electrolytes and renal function. But even though we haven’t got certain outcomes, the research goes on quickly and some other sites of modulation of RAS were identified, from its first phases (aliskiren as prototype of direct renin inhibitors).