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182 Hypertonie 2011 - Poster Hypertonie 2011 - Poster 183
vs 27,7 %) und Diabetes (62,1 vs 24,3 %) auf. Die
absolute Blutdrucksenkung war am stärksten
unter Aliskiren 18,9±20,7/9,8±12,8 mm Hg) vs
ACE-I/ARB (16,5±24,6/7,8 mm Hg) vs Non-RAS
(12,7±18,0/9,2±12,3 mm Hg) (p< 0.05/0,13). Die
relative Blutdrucksenkung im Verhältnis zum
Ausgangsblutdruck bestätigte die Überlegen-
heit von Aliskiren (11,0±11,6 /9,4±13,9 %) vs
ACE-I/ARB (9,3±15,2/7,3±14,5 %) vs Non-RAS
(7,6±11,5/8,7±14,2 %) (p< 0,05/p=0,14)
Schlussfolgerungen: Eine Analyse der Versorgungsstudie
3A Register bei Patienten mit Proteinurie
zeigte signifikante Unterschiede in der
systolischen Blutdrucksenkung nach 1 Jahr
zugunsten Aliskiren. Proteinurie wird zu selten
bei Hypertoniepatienten untersucht
Pharmakologie und Pharmakotherapie
II
PS 56
Superior Blood Pressure Reduction
During 2-Year Follow-Up with Aliskiren in
Hypertensive Patients in Real Life. Results of
the 3A Registry
Zeymer U. 1,2 , Dechend R. 3 , Kaiser E. 4 , Deeg E. 2 ,
Schmieder R. 5
1Klinikum Ludwigshafen, Ludwigshafen, Germany,
2Institut für Herzinfarktforschung Ludwig-
3 hafen, Ludwigshafen, Germany, HELIOS
Klinikum Berlin-Buch, Berlin, Germany,
4Novartis Pharma GmbH, Nürnberg, Germany,
5Universitätsklinikum Erlangen, Nephrologie
und Hypertensiologie, Erlangen, Germany
Background: Blockade of the renin angiotensin
aldosterone system is recommended
in patients with arterial hypertension. The new
direct renin inhibitor has been shown to be effective
and safe in hypertensive patients in randomized
clinical trials. However, there are only
few prospective data on blood pressure control
in patients with the direct renin inhibitor aliskiren
in a daily practice setting available.
Methods: In the non-interventional 3A Registry
patients were eligible for inclusion in whom
the physician had decided to modify the antihypertensive
therapy. This included treatment
with the direct renin inhibitor aliskiren or an
ACE inhibitor (ACE-I)/angiotensin receptor
blocker (ARB) or agents not blocking the reninangiotensin-system
(RAS), alone or on top of
an existing drug regimen. Patients were prospectively
followed for one year. Here we report
the for the first time the results of the 2-year
follow-up.
Results: Of the 14988 patients recruited by 923
physicians in Germany in 2008 and 2009, two
year follow-up has been available in 61%.
Patients with aliskiren showed better blood
pressure reduction after two years than patients
with ACE-I/AR or without RASS-blockade both
in the office blood pressure (mean reduction in
BP in %: 12.9+12/10.3+14 vs. 10.9+13/8.5+13 vs
10.5+12/9.0+13; p-value < 0.001/< 0.01) and in
the 24-hr ambulatory blood pressure (mean reduction
in % , 8.4+11/7.7+12 vs. 6.3+11/5.4+12
vs. 7.2+9/6.6+10; p-value < 0.05/0.05).
Conclusions: In this large real life registry in
hypertensive patients an aliskiren-containing
regimen showed better blood pressure reductions
after 2 years than patients without RASblockade,
or an ACE-I/ARB-containing regimen.
These results support the findings from
randomised clinical trials
PS 57
Benzimidazole-Derived New PPARgamma
Agonists Act Like Selective Modulators
Herbst L. 1 , Goebel M. 2 , Bandholtz S. 3 , Gust R. 4 ,
Kintscher U. 1
1Charite - Universitätsmedizin Berlin, Inst. of
Pharmacology, Berlin, Germany, 2Charite -
Universitätsmedizin Berlin, Inst. of Pharmacy,
Berlin, Germany, 3Charite - Universitätsmedizin
Berlin, Inst. of Gastroenteroloy, Berlin, Germany,
4University of Innsbruck, Inst. of Pharmacy,
Innsbruck, Austria
Activation of the peroxisome proliferator-activated
receptor gamma (PPARγ) exhibits beneficial
effects on the regulation of genes involved
in glucose and lipid metabolism. However,
the currently used synthetic PPARγ agonists,
the thiazolidinediones, lead to increased body
weight, fluid retention and increased risk for
heart failure. These side effects reveal the need
for further investigation of favorable PPARγ ligands.
Besides its antihypertensive properties, the angiotensin
type 1 (AT1) receptor blocker telmisartan
has been shown to act as partial agonist of
PPARγ. In the present study we characterized
new PPARγ agonists (compounds 1-3) based
on the structure of telmisartan to develop new
therapeutic strategies against insulin resistance
and type 2 diabetes mellitus. PPARγ is the
“master regulator” of adipocyte differentiation,
and its activity closely correlates with the degree
of differentiation. Adipocyte differentiation
assay was performed with 3T3-L1 cells and analyzed
by Oil-Red O staining. Cells stimulated
with compounds 2 and 3 show a stronger differentiation
grade compared to telmisartan at
1µM and 10µM and a similar differentiation level
like the full agonist pioglitazone. Luciferase assay
with COS-7 cells, transiently transfected with
pGal4-hPPARγDEF, pGal5-TK-pGL3 and pRL-
CMV confirmed the results of Oil-Red O staining.
Compared to pioglitazone, luciferase activity
increased more pronounced with compound
3. For further characterization, we performed
ligand-binding domain (LBD) studies using
time-resolved Fluoreszenz-Resonanz-Energy-
Transfer with the corepressor NCoR1 and the
coactivators PGC-1α, SRC-1 and TRAP220.
Binding of our compounds to the PPARγ-LBD
caused a conformational change which resulted
in dose-dependent release of NCoR1 similar
to telmisartan and pioglitazone and selective
coactivator recruitment. Microarray analysis
and qRT-PCR showed a differential geneexpression
under distinct agonist stimulation.
Here, we reported new PPARγ ligands with partial
and full agonistic receptor activation and selective
cofactor recruitment/gene expression.
Thus, these new PPARγ ligands act like SP-
PARMs. Metabolic efficacy of these compounds
needs to be elucidated in the future.
PS 58
High Dose Olmesartan Compared to
Amlodipin Is Superior in Lowering Central
Systolic Blood Pressure and Ambulatory
Blood Pressure in Patients with Metabolic
Syndrome
Raff U. 1 , Walker S. 1 , Ott C. 1 , Schneider M.P. 1 ,
Schmieder R.E. 1
1Friedrich-Alexander Universität Erlangen-
Nürnberg, Medizinische Klinik 4, Nephrologie
und Hypertensiologie, Erlangen, Germany
Objective: The metabolic syndrome (MetSyn) is