1 Introduction

The 2013 ESH/European Society of Cardiology (ESC) guidelines state that monotherapy and combination therapy can be used as appropriate and propose the treatment algorithm shown in Fig. 1 [1]. The first step in pharmacological therapy is the choice of antihypertensive drugs. Diuretics, β-blockers, calcium channel blockers (CCBs), angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs) are all suitable and recommended [1]. Clinical trials show that the majority of patients require at least two agents to achieve goal BP and that two drugs are five times more effective than one [2–4]. It is important to note that, for the major drug classes, the incremental effect of doubling the monotherapy dose on systolic BP (SBP) is only about 20 % of that achieved by adding a drug from another class [5]. As a result, the use of combination therapy has been recommended by guidelines since 2003. In addition to efficacy gains, some combinations can also reduce drug-related side effects, such as CCB-induced ankle oedema [6, 7], and are recommended by ESH/ESC 2013 guidelines. In a randomised, double-blind, parallel group, multicentre study, adding olmesartan (OLM) to amlodipine (AML) significantly improved antihypertensive efficacy in patients with an inadequate response to monotherapy (Fig. 2) [8].

Fig. 1
figure 1

Hypertension treatment algorithm (modified from Mancia et al. [1])

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Fig. 2
figure 2

Blood pressure reduction with amlodipine (AML) alone and in combination with olmesartan (OLM) (modified from Volpe et al. [8])

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2 Strategies to improve adherence

When needed, efficacy can be improved by adding a third agent to a two-drug combination regimen [9]. A triple combination therapy, with hydrochlorothiazide (HCTZ) added to OLM/AML, was evaluated in a randomised, double-blind, parallel group, multicentre study, and was superior to the two-drug combination across a range of doses (Fig. 3) [10]. More recently, the BP-CRUSH study, a multicentre, prospective, open-label, single-arm, dose-titration trial, showed that nearly all patients achieved BP <140/90 mmHg with stepwise OLM/AML/HCTZ therapy [11].

Fig. 3
figure 3

Blood pressure reductions during treatment with olmesartan (O)/amlodipine (A) alone and with the addition of hydrochlorothiazide (H) (modified from Volpe et al. [10])

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Moreover, single-pill fixed-dose combinations (FDCs) can reduce pill burden and simplify treatment regimens [1]. Adherence/compliance in hypertensive (HTN) patients typically falls over time and tolerability has been shown to affect drug use [12]. According to Italian Health Service data, ARBs were the most well-tolerated drug class, with the lowest rate of discontinuation; within this, the discontinuation rate was lowest for OLM [13]. Good adherence to antihypertensive therapy decreases cardiovascular (CV) risk. Compared to patients with low (<80 %) adherence, those with high (≥80 %) adherence were less likely to develop chronic heart failure [14], coronary artery disease [15] and cerebrovascular disease [16].

FDCs have other important benefits over giving the same individual agents separately: improved BP control and normalisation rates [17]; increased compliance (particularly in older patients) [18, 19]; improved persistence on treatment [20]; and reduced total and CV-related hospitalisation costs [21]. These are all reasons underlying the 2013 ESH/ESC guideline recommendation for the use of FDCs containing two or three agents [1].

Very recently, Volpe et al. [22] proposed an ARB-based single pill strategy that includes an ARB alone or in combination with AML and/or HCTZ. The strategy outlines appropriate therapy for patients with varying characteristics and needs, based on clinical evidence, guidelines, best practice and clinical experience. Efficacy should be assessed after 2–4 weeks and treatment intensified if required. To improve adherence, the use of a FDC is recommended. Essentially, this strategy is based on OLM, which is available as monotherapy and in FDCs with AML and/or HCTZ. In addition, the triple OLM/AML/HCTZ single-pill combination is the only ARB-based triple combination with an add-on indication in Europe. The ARB platform recommends specific treatment algorithms for patients with specific risk factors or subclinical organ damage (OD) and patients with overt OD (Table 1A, B), and outlines how the majority of patients with HTN can be effectively treated in general practice with an ARB like OLM, combined with AML and/or HCTZ.

Table 1 ARB-based strategy: treatment algorithm for patients with HTN and specific risk factors and subclinical (A) or overt (B) organ damage (reproduced with permission from Volpe et al. [22])
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3 Conclusions

Monotherapy and combination antihypertensive therapy can be used to effectively treat patients with hypertension in clinical practice. The majority of people with hypertension will require two or three antihypertensive agents to achieve optimal BP. The ESH/ESC guidelines recommend the use of FDCs of two or three agents in clinical practice to effectively achieve goal BP in patients with hypertension, as single-pill FDCs have been shown to improve adherence to medication as well as BP control.