The use of antihypertensive fixed combinations in clinical practice needs a reappraisal.

Abstract

Listen

Translate article

The treatment of arterial hypertension requires the use of combination therapy, either fixed-dose or free-dose, in the majority of patients with hypertension.1 Many different fixed-dose combinations have appeared in the past decades in an attempt to facilitate blood pressure (BP) control while maintaining better adherence and compliance. This was initially shown to be the case during the first year of use of fixed-dose combinations,2 even in moderate to severe hypertension.3 In fact, the most widely used fixed- or free-dose combinations, recommended by most guidelines, includes a renin-angiotensin blocker (angiotensin-converting enzyme inhibitor or angiotensin receptor blocker) with a calcium channel blocker or a diuretic in double combinations, and the three drugs in triple fixed- or free-dose combination. The selection of these drugs to be combined either as free- or fixed-dose combinations is based on the demonstration of the advantages of using an initial combination that besides attaining a more rapid initial BP control reduces cardiovascular events in patients with hypertension during the follow-up.4 Furthermore, the combination of an angiotensin-converting enzyme inhibitor with a dihydropyridine calcium channel blocker has been shown to be more protective than an angiotensin-converting-enzyme inhibitor with a diuretic.5 The article by Bramlage and colleagues6 in this issue of the Journal of Clinical Hypertension reviews the data obtained in a cohort of more than 80 000 patients in Germany. Registries of BP are relevant because they contribute to direct practice and also to finding the most adequate apportionment of resources.7 Theoretically, this real-world evidence is perfectly compatible with a planned intervention or the use of a randomization,8 but frequently, as is the case with the data in the present article, the real-world data do not contemplate the application of the conclusions obtained to the most adequately performed clinical trials contained in guidelines. As can be seen in the trial, fixed-dose combinations are used only in a minority of the patients compared with free combinations and they are more often used in patients with lower risk according to the presence of comorbidities. In fact, in patients receiving free-dose combinations, a higher proportion was receiving three or more drugs before entering the registry. This favors the concept of more difficult to control hypertension, or even resistant hypertension, in this group. Interestingly, the magnitude of the change in BP during follow-up was not different between the two series of patients, but confirming the available data even in daily life practice9 persistence/adherence was better when fixed-dose combinations were used. The interpretation of the data seen in this article is challenging. First, it can be considered that doctors do not follow guidelines on the use of fixed-dose combinations. Second, when the risk is clearly elevated, they may feel more comfortable with free combinations that allow a wider use of doses, albeit the need for addition of new drugs could contribute to the decrease in persistence/adherence. Third, the finding of similar BP control with the two therapeutic attitudes fits well with the hesitation of doctors in relation to reduce elevated BP to goal levels.10 Otherwise, the control should have been more intense in relation to the risk elevation, which is not the case in the present article. The data contained in this publication indicate that a reappraisal of the use of fixed-dose combinations in daily clinical practice is required in order to obtain the advantages demonstrated in clinical trials and cohort studies on the protection of cardiovascular and renal damage in patients with hypertension.