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Jc2
1. Hypertension (2)
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RJS Journal Club
J Am Soci Hypertension 14:299-306, 2012
2. Aliskiren (trade names
Tekturna)
It is the first in a class of drugs called
direct renin inhibitors approved by FDA
in 2007 and currently licensed for Rx of
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RJS Journal Club
essential (primary) HTN.
5. ABPM
National Institute for Health and Clinical
Excellence (NICE 英國國健局 ) recommends
that ABPM be used to confirm the
diagnosis of primary hypertension as it is a
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RJS Journal Club
better predictor of cardiovascular events
than BP measured at the clinic.
6. Blood Pressure (BP) load
BP load is defined as percentage of BP
readings exceeding the upper limits of
normal (130/80 mmHg) for a given time
period.
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RJS Journal Club
BP load has a strong predictive value for
end-organ damage.
8. Nondipper HTN Pattern
The blunted nocturnal fall in BP, referred to as
nondippers, is mediated by activation of the
renin-angiotensin-aldosterone system (RAAS).
A nondipping circadian BP pattern is estimated
to affect up to 40% of the HTN population; it is
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RJS Journal Club
a marker for increased target-organ damage and
cardiovascular risk.
A recent prospective analysis has shown a 17%
reduction in cardiovascular risk with each 5-mm
Hg reduction in nighttime systolic BP.
9. PRA and Nocturnal BP
Nocturnal systolic and diastolic BP dips are
negatively correlated with basal PRA, i.e.,
the more the plasma level of PRA is
increased, the less likely there is nocturnal
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RJS Journal Club
fall in BP.
Thus, RAAS blockers such as ACEI, ARB,
and DRI (direct renin inhibitors) might be
useful in this clinical setting.
10. RJS Journal Club
RJS Journal Club
Physiology of RAAS
Thieme Publishers All rights reserved
11. Methods
A pooled analysis of ABPM data from two
randomized controlled trials was
performed to compare the
antihypertensive efficacy and safety of
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RJS Journal Club
RAAS blockade with combination DRI⁄ARB
(aliskiren ⁄ valsartan) vs ARB alone
(valsartan) in patients stratified as
nocturnal dippers or nondippers.
12. Definition
Dippers are randomized patients whose
nighttime (10 PM to 6 AM) mean
ambulatory systolic BP (maSBP) dropped
>10% below their daytime (6 AM to 10
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RJS Journal Club
PM) baseline values.
Nondippers included randomized patients
whose nighttime maSBP dropped <10%
below their daytime baseline values.
14. Pertinent Findings
Nondippers tended to be slightly older
than dippers (54.6 vs 53.3 years), to be
somewhat more obese (BMI 30.8 vs 30.0
kg ⁄m2), and to have greater baseline
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RJS Journal Club
ambulatory BP (145.7 ⁄ 92.4 vs 142.4 ⁄ 89.9
mm Hg).
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RJS Journal Club
FIGURE 3. Reductions from baseline to week 8 in mean ambulatory systolic
blood pressure (maSBP) during the nighttime and daytime and during
the last 4 hours of the 24-hour dosing period in nocturnal dippers and
nondippers. LSM indicates least-square mean.
16. Combo before tx mono before tx
Combo after tx mono before tx
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RJS Journal Club
Hourly (a) mean ambulatory systolic blood pressure (maSBP) and (b)
mean ambulatory diastolic blood pressure (maDBP) at baseline
and week 8 in nocturnal dippers and nondippers.
17. Conclusions
The addition of aliskiren to valsartan was
associated with an incremental benefit of
approximately 5 to 6 mm Hg of lowering
in mean ambulatory systolic BP and
approximately 3 to 4 mm Hg of lowering
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RJS Journal Club
in mean ambulatory diastolic BP. Of note,
32% of patients were converted from a
nondipper at baseline to a dipper status at
the end of study.
18. Clinical Implications
Optimal treatment of the nondipping
circadian BP pattern is probably best
managed with drugs that inhibit the RAAS,
with the combination of a DRI and an ARB
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RJS Journal Club
providing greater efficacy and similar
safety as an ARB alone.
19. A Warning from Novartis
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RJS Journal Club
2012 / 01 / 02
20. Action Points
ABPM is required to differentiate nocturnal
dipper and non-dipper HTN patients.
In nocturnal non-dipper HNT patients,
anti-RAAS drugs should first be
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RJS Journal Club
considered.
Combination of DRI and ARB is effective
for non-dipper HTN patients, but serious
adverse side effects (stroke, renal
damage, hyperkalemia, etc.) of this
