[Combination therapy in arterial hypertension: how to personalize treatment]

Combination therapy is necessary in approximately 70% of hypertensive patients to achieve adequate blood pressure control. Furthermore, fixed combinations have a documented clinical utility as they increase therapeutic adherence. The most effective combinations of antihypertensive drugs are those made with drugs that have a complementary effect on the blood pressure regulation systems. In other words, it is rational to combine drugs that block the renin-angiotensin system or the sympathetic nervous system with drugs that activate these systems. Therefore, with regard to antihypertensive efficacy, both the fixed combination ACE-inhibitor/calcium channel blocker and the fixed combination AT1 antagonist/calcium channel blocker are rational as they have an additive effect on blood pressure reduction and improve the tolerability of the individual molecules. However, the choice of a combination therapy should not be limited only to evaluating the efficacy on blood pressure levels, but a more important target is certainly the ability to reduce cardiovascular events. As regards calcium channel blockers, the molecule with the best evidence of clinical efficacy in randomized controlled studies is certainly amlodipine (VALUE, CAMELOT, PREVENT, CAPARES, ASCOT and ACCOMPLISH studies). Also as regards ACE-inhibitors, the use of ramipril is supported by a significant series of clinical studies (HOPE, micro-HOPE and AIRE). In accordance with their efficacy, both molecules are the most used in daily clinical practice. It is however necessary to underline that, among AT1 antagonists, the best scientific literature certainly supports the efficacy of candesartan (SCOPE, TROPHY, AMAZE, CALM and DIRECT studies) which should therefore be the reference molecule in clinical use. Therefore, the combinations of ramipril/amlodipine and candesartan/amlodipine represent a therapeutic opportunity of primary importance as they combine the ACE-inhibitor, AT1 antagonist and the calcium channel blocker with the best documentation of efficacy in randomized controlled trials.In conclusion, the support of the scientific literature indicates that the rational use of these combinations can certainly represent an optimal choice for the treatment of arterial hypertension according to the best criteria of therapeutic appropriateness.