Modern clinical management of arterial hypertension: fixed or free combination therapies?

Blood pressure control is a key element in any cardiovascular prevention strategy. However, it is also one of the least frequently achieved goals in modern strategies for the clinical management of cardiovascular diseases, resulting in high impact in terms of cardiovascular morbidity and mortality. Among different factors that can be identified as the causes of poor blood pressure (BP) control in the general population of patients with hypertension, the excessive use of monotherapy, as opposed to combination therapy, is arguably one of the most significant. In this perspective, the use of combination therapies having synergic and complementary actions has been shown to reduce BP levels to increase the percentage of patients who respond to antihypertensive treatment and achieve the recommended BP targets. Moreover, recent studies have demonstrated that these strategies provide effective protection against hypertension-related organ damage, as well as a significant reduction of major cardiovascular events. While currently available evidence supports an increasingly important role of combination therapies compared with monotherapies, several other issues remain to be clarified. Among these, it has not yet been clearly established which classes of drugs should be considered for combination strategies, at what doses each component should be used, and whether combination strategies may be definitively considered as a first choice for the treatment of hypertensive patients at cardiovascular risk. Another relevant aspect concerns the choice between fixed and free combination therapies. This article discusses and analyses the different factors that may contribute to achieve effective BP control. In particular, the potential benefits and drawbacks associated with the use of fixed versus free combination therapies for hypertension treatment will be examined and discussed. The benefits of using combination strategies based on drugs that antagonize the renin-angiotensin system and dihydropyridine calcium antagonists will also be discussed, with a particular focus on amlodipine besylate combination therapies.