EDITORIAL

Achieving better blood pressure control

THOMAS HEDNER, SUZANNE OPARIL, KRZYSZTOF NARKIEWICZ & SVERRE

E. KJELDSEN

Primary hypertension is a polygenic condition with

variable contribution from environmental factors.

Not surprisingly, there are differential responses to

both non-pharmacological and pharmacological

antihypertensive treatments within the population

of hypertensive patients. In order to achieve maximal

risk reduction, blood pressure (BP) should be

reduced to below 140/90 mmHg in lower risk

hypertensive patients, and even lower (v130/

80 mmHg) if additional risk factors such as diabetes

or renal disease are present (1). Despite the

availability of multiple classes of antihypertensive

agents that lower BP by different mechanisms, the

treatment of hypertension remains a difficult task. In

terms of BP lowering effects, it is usually not possible

to predict which type of agent is the most appro-

priate for a given patient. Consequently, in most

hypertensive patients, target BPs are usually not

reached by the use of monotherapies (2,3).

However, a strategy of combining medications

acting by different mechanisms makes it possible to

achieve considerable gains in terms of antihyperten-

sive efficacy. This is due to the synergistic effects on

the cardiovascular system of antihypertensive med-

ications that have distinct mechanisms of action (4).

When combining two or several antihypertensive

medications from different classes, it is important to

select combinations of drugs that have complemen-

tary effects on BP lowering as well as reduction of

adverse events (1). In recent years, use of fixed-low-

dose combinations of antihypertensive medications

as first-line treatment has increased greatly, since

studies have shown that this approach is likely to

both increase the chance of controlling the patient’s

BP and limit the occurrence of dose-related adverse

effects (5,6).

In the present issue of Blood Pressure, Ruilope and

co-workers (7) argue for wider use of fixed-

dose antihypertensive combinations based on both

individual patient benefits and, importantly, also on

greater public health and societal value. This Drug

Therapeutic Supplement also deals with the issue of

which drugs to combine. As demonstrated by

Tuomilehto et al. (8) and Schumacher and Mancia

(9), a fixed-dose angiotensin II receptor blocker

(ARB)-diuretic combination has greater or compar-

able antihypertensive efficacy than ARB treatment

alone without reduced tolerability. Most combina-

tion regimens currently available for clinical use

include an inhibitor of the renin–angiotensin system

(RAS) and a diuretic, but a fixed-dosed combination

regimen that includes a calcium-channel blocker and

an angiotensin-converting enzyme (ACE) inhibitor

is also widely used and has recently been shown to

have outcome advantages over a combination of the

same ACE inhibitor and a diuretic in the

ACCOMPLISH trial (10). Ueng et al (11) demon-

strate that the dihydropyridine calcium-channel

blocker amlodipine and the ACE inhibitor benaze-

pril, when combined, have complementary effects on

BP, with impressive efficacy in rapid attainment of

BP targets as well as levels of BP achieved.

Importantly, as pointed out by Ruilope and

coworkers (7), combinations of drugs from different

antihypertensive classes may have both synergistic or

additive antihypertensive properties and the ability

to diminish each others’ untoward hemodynamic or

metabolic effects. Importantly, beneficial fixed-dose

combinations containing optimal doses can be

selected as initial therapy, thereby facilitating rapid

BP control and minimizing adverse effects in the

newly diagnosed hypertensive (6).

Poor control of hypertension remains an issue in

most parts of the world. Failure to attain BP goals is

related to multiple factors, e.g. insufficient efficacy

of available single antihypertensive agents, poor

adherence to prescribed medication, and reluctance

of many physicians to treat aggressively, including

Blood Pressure. 2008; 17 (Suppl 1): 3–4

ISSN 0803-8023 print/ISSN 1651-2480 online # 2008 Taylor & Francis

DOI: 10.1080/08038020802184504

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combining antihypertensive medications to reach

target BPs (5). Most guidelines for the management

of high BP advocate a strategy of early combination

therapy with low doses of two antihypertensive drugs

for management of mild/moderate arterial hyperten-

sion. Recent evidence suggests that this strategy may

be preferred over monotherapy (5). The superior

effectiveness of low-dose fixed-dose combination

therapy relates to both better antihypertensive

efficacy and higher BP response rates, in part due

to improved medication adherence, and to greater

tolerability due to reduced rates of adverse effects

(12). In addition, fixed-dose combination therapy

often costs less than free combinations of the

component drugs. Because of all of these benefits,

increased use of low dose fixed combination

therapies will likely translate into a further reduction

of hypertension-related cardiovascular/cerebrovas-

cular morbidity and mortality in the population (13).

References

1. 2007 ESH-ESC Guidelines. Blood Press. 2007;16:135–232.

2. Waeber B, Brunner HR. Joint National Committee in the US

(JNC-VI); World Health Organization–International Society

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hypertension: The greatest challenge for its treatment? J

Hypertens. 2001;19 Suppl:S9–S16.

3. Elliott WJ. What factors contribute to the inadequate control

of elevated blood pressure? J Clin Hypertens (Greenwich).

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4. Waeber B. Fixed low-dose combination therapy for hyperten-

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11. Ueng K-C, Lin L-C, Voon W-C, Lin M-C, Liu Y-B, Su H-

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4 Editorial

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