Achieving better blood pressure control

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  • 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 patients

    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 reninangiotensin 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): 34

    ISSN 0803-8023 print/ISSN 1651-2480 online # 2008 Taylor & FrancisDOI: 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;16:135232.

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

    (JNC-VI); World Health OrganizationInternational Society

    of Hypertension (WHO-ISH) The multifactorial nature of

    hypertension: The greatest challenge for its treatment? J

    Hypertens. 2001;19 Suppl:S9S16.

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

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

    2008;10 Suppl 1:2026.

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

    sion. Curr Hypertens Rep. 2002;4:298306.

    5. Ruzicka M, Leenen FH. Monotherapy versus combination

    therapy as first line treatment of uncomplicated arterial

    hypertension. Drugs. 2001;61:943954.

    6. Rosenthal T, Gavras I. Fixed-drug combinations as first-line

    treatment for hypertension. Prog Cardiovasc Dis.

    2006;48:416425.

    7. Ruilope LM, Burnier M, Muszbek N, Brown RE,

    Keskinaslan A, Ferber P, et al. Public health value of fixed-

    dose combinations in hypertension. Blood Press. 2008;17

    Suppl 1:413.

    8. Tuomilehto J, Tykarski A, Baumgart P, Reimund B, le

    Breton S, Ferber P. Combination therapy with valsartan/

    hydrochlorothiazide at doses up to 320/25 mg improves blood

    pressure levels in patients with hypertension inadequately

    controlled by valsartan 320 mg monotherapy. Blood Press.

    2008;17 Suppl 1:1422.

    9. Schumacher H, Mancia G. The safety profile of telmisartan as

    monotherapy or combined with hydrochlorothiazide: A

    retrospective analysis of 50 studies. Blood Press. 2008;17

    Suppl 1:3139.

    10. Kjeldsen SE, Jamerson KA, Bakris GL, Pitt B, Bahlof B,

    Velazques EJ, et al., for the ACCOMPLISH Investigators.

    Predictors of blood pressure response to intensified and fixed

    combination treatment of hypertension: The ACCOMPLISH

    Study. Blood Press. 2008;17:717.

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

    M, et al. An eight week, multicenter, randomized, double-

    blind study to evaluate the efficacy and tolerability of fixed-

    dose amlodipine/benazepril combination with amlodipine as

    first-line therapy in Chinese patients with mild to moderate

    hypertension. Blood Press. 2008;17 Suppl 1:2330.

    12. Bangalore S, Kamalakkannan G, Parkar S, Messerli FH.

    Fixed-dose combinations improve medication compliance: A

    meta-analysis. Am J Med. 2007;120:713719.

    13. Kjeldsen SE, Oparil S, Narkiewicz K, Hedner T. A stunning

    day in hypertension research Results on ONTARGET,

    ACCOMPLISH and HYVET. Blood Press. 2008;17:6869.

    4 Editorial

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