achieving better blood pressure control
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Achieving better blood pressure control
THOMAS HEDNER, SUZANNE OPARIL, KRZYSZTOF NARKIEWICZ & SVERRE
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
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
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).
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.
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
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
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.