Comparing the therapeutic merits of angiotensin receptor blockers

Successful control of blood pressure (BP) remains suboptimal in many jurisdictions [1]. Although there are many reasons for this, the considerable prevalence of hypertension is a challenge [2]. More than one quarter of adults in Western populations have high BP. In addition to being the leading attributable risk factor for death throughout the world, hypertension results in substantial illness due to its effect on several target organs, including the brain, eyes, heart, arteries, and kidneys [3–6]. It is the most common reason for a consultation at primary care level in which the majority of its management takes place. In addition to nonpharmacologic interventions, most individuals require antihypertensive medication to lower BP and often require them in combination. An understanding of the mode of action and complementary features of differing BP medications is important. The greater use of ‘out of office’ measurements highlights the need to use medications that offer good 24-h BP control and possibly have a complementary effect on indices, such as BP variability and the morning surge [7–10]. Although lifestyle modification is important in hypertension management, most hypertensive individuals require more than two antihypertensive drugs to reduce their BP and maintain it within acceptable ranges [11–13]. The effectiveness of at least five classes of drugs used in treating hypertension and preventing cardiovascular events is well documented [12]. Yet there are differences in the therapeutic characteristics of medications within BP lowering classes [14]. The most commonly used medications among the many choices in antihypertensive therapy are those aimed at inhibiting the renin–angiotensin–aldosterone system. In this issue of Journal of Hypertension, there is an interesting article from Satoh and colleagues [15] evaluating a number of therapeutic characteristics of AT1 blockers, including ‘velocity of maximal effect’ or stabilization time, by which is meant the time interval from starting the medication to when it has its maximal effect. While the authors have described this time index previously, in this article, they evaluate seven different AT1 blockers, all used at medium dosage as monotherapy in patients referred to a specialist clinic for hypertension [16,17]. The drugs were compared in relation to the magnitude of the BP-lowering effect and the rapidity with which this maximum effect was achieved. The velocity or stabilization time based on morning home-BP readings differed significantly within the drug class. The magnitude of effect also varied, and Fig. 2 in Satoh et al. [15] might assist clinicians in their medication selection and follow-up of patients. The extent of BP-lowering effects of azilsartan was significantly greater than that of valsartan or irbesartan. The stabilization time of losartan based on home-SBP was significantly longer than that of azilsartan, valsartan, or irbesartan [15]. The authors suggest that clinicians should be aware of these varying characteristics when selecting medications for different population groups, for example, in the elderly or those with severe hypertension, when the time taken to achieve control might be relevant. The study has some limitations that need to be considered. There may be some inherent bias in the selection of patients as this was a retrospective analysis of existing patient records. Some attempt was made to standardize the BP levels across the cohorts but there may have been underlying reasons why certain medications were used for some patients. There is also an issue regarding the selection of patients. Only patients on monotherapy were included. By virtue of this, responders were more likely to be included in the study, and we have no background information as to which drug had a higher ratio of responders, and there may be an overestimation of the true BP-lowering effect of some of the medications. Furthermore, the relatively small number of patients studied and evaluation after administration of only one dose of the AT1 blocker was evaluated, which may have reduced the consistency of the results and thus not reflecting the prescribed practice. However, in a recent meta-analysis, a shallow dose–response curve was observed for AT1 blockers, with up-titration only marginally enhancing the antihypertensive efficacy. BP reduction with losartan at starting dose and at max dose was consistently inferior to the other AT1 blockers [18]. Out-of-office measurements were utilized, and the authors only included early-morning home monitoring measurements as a trough marker for the BP-lowering effect [15]. It would perhaps be of interest had ambulatory BP measurements been available to evaluate the BP-lowering effect over 24 h at some time point after initiation. This would have given an insight into the degree of BP reduction over the 24-h period and also the varying effects on a range of ambulatory BP indices. Fabia and colleagues [19] previously showed in an earlier meta-analysis that AT1 blockers differed significantly in their duration of action which would have influenced morning BP readings. There are nonetheless some important messages from this work that we should heed in the management of sometimes complex hypertensive patients. Home monitoring, as nicely illustrated in this study, provides the prescribing clinician with early reliable information on the therapeutic response and the need for dose escalation or addition of further antihypertensive agents [20,21]. The technique can also prompt patients to return to the clinic earlier if they are concerned about persistently elevated home readings despite therapy, or they might be facilitated in titrating their own medications as instructed [22,23]. It allows a sharing of responsibility with the patient. Many hypertension guidelines advocate the use of out-of-office measurements for the diagnosis of hypertension; however, many have been slow to recommend it for follow-up assessment of hypertensive patients [12,24]. This is regrettable and may be assisted by the introduction of new devices that will allow for the measurement of BP in the clinic, at home and also can be set to measure BP over the 24-h period. With such devices to hand, we can combine the complementary benefits of ambulatory BP and home monitoring for our patients. Finally, our understanding of what targets to treat our patients to has changed following the publication of the SPRINT study [25]. This landmark trial has shown in a certain category of perhaps lower-risk hypertensive patients that a more intensive BP-lowering regime seems to improve outcome. Returning to Fig. 2 in Satoh et al.[15], this raises the question of whether we should just use the most potent agent so as to provide patients with maximum benefits in the shortest time. Unfortunately, managing hypertension is not always that straightforward in sometimes complex patients. We must individualize our therapies and use out-of-office measurements to assist us in doing so. ACKNOWLEDGEMENTS Conflicts of interest There are no conflicts of interest.