Mancia 30/7/08 4:02 pm Page 76
Hypertension
Figure 1: TALENT Study Design
One other potential advantage of initiating treatment with two drugs
has emerged more recently: the rate of blood-pressure control is
0 weeks 8 weeks 16 weeks
improved compared with that obtained when treatment starts with a
Double-blind treatment Double-blind treatment single drug and moves to combination only at a later time. The TALENT
study allows this specific issue to be addressed, as:
Nifedipine GITS 20mg • in one group treatment is started with nifedipine GITS 20mg plus
+ telmisartan 80mg
telmisartan 80mg, a regimen that is maintained unchanged
throughout the 16 weeks of the study; and
Optional 8-week • in the other two groups treatment starts with telmisartan 80mg or
extension of
combination
nifedipine GITS 20mg, and the two drugs are administered in
Nifedipine GITS 20mg
Nifedipine GITS 20mg
+ telmisartan 80mg
therapy with
combination only after eight weeks, i.e. halfway through the study.
uptitration of
nifedipine GITS
as required
In both groups the goal of treatment is to reduce blood pressure
to <130/80mmHg, as required by the high-risk conditions of the
recruited patients.
Telmisartan 80mg
The importance of strategies that improve the rate of blood-pressure
control cannot be overemphasised. Evidence from all available data
indicates that worldwide only a limited number of hypertensive patients
Figure 2: Calcium-channel Blockers Are the Preferred Drug
Class in Many Antihypertensive Combination Strategies
have their blood pressure reduced to <140/90mmHg,
2
and that only a
minute fraction of high-risk individuals achieve the more aggressive
Diuretics
goal recommended by guidelines (<130/80mmHg).
15
This is presumably
the reason why hypertension still stands as the number one cause of
death worldwide.
16
β-blockers ARBs It is generally agreed that the poor rate of blood-pressure control in the
hypertensive population results from the interplay of several complex
factors, including insufficient use of combination treatment. As
mentioned by the ESH/ESC guidelines (see Figure 2),
2
however, an
additional reason can be the frustration experienced following an initial
unsuccessful monotherapy (particularly if followed by other
monotherapy attempts), which can demotivate the patient and favour
α1-blockers CCBs
the clinical inertia of the physician. The demonstration in TALENT that
initiating treatment with a combination of drugs leads to a greater rate
of blood-pressure control would thus be a result of general importance.
ACE inhibitors
Other Goals
The TALENT study also has other interesting goals. One of them is to
Continuous lines show two-drug combinations that have been found to be well tolerated and effective.
Mancia G et al., Eur Heart J, 2007;28:1462–1536. Reproduced with permission from Eur Heart J.
look for a number of efficacy parameters based on ambulatory blood-
pressure monitoring data, among them the smoothness index. This
drugs being added only if needed to effectively reduce blood pressure. can determine more effectively than the classical trough-to-peak ratio
However, more recently this position has changed and physicians are how homogeneous the blood pressure fall induced by treatment is
presented with two options: either to start treatment with one drug or over 24 hours, with consequences for blood-pressure variability and
to use two drugs from the beginning if a patient can be classified as for the protection of the organs exposed to the damage induced by a
being at high cardiovascular risk.
2,13
This has originated from the blood-pressure elevation.
17
evidence that:
Another goal is to measure the antiproteinuric effect of the
• in a high-risk individual the chance of a morbid or fatal combination of nifedipine GITS and telmisartan compared with the
cardiovascular event within a short time period is not negligible; two combination components as monotherapy. This has important
clinical implications because both microalbuminuria and proteinuria
• blood-pressure control has been shown to reduce the event rate as predict the incidence of cardiovascular events, their reduction in turn
early as a few months after the beginning of treatment; and being associated with a better prognosis in both diabetic and non-
diabetic individuals.
18,19
• in the VALUE study, patients in whom blood-pressure control was
achieved early (within one month) had fewer events compared with Finally, the TALENT study includes the measurement of inflammatory
those in whom it was achieved later.
14
markers. This is an emerging area of interest in hypertension due to
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