Bir ARB Olarak Olmesartan - TurkHipertansiyon · Bir ARB Olarak Olmesartan ... (Prevalence,...
Transcript of Bir ARB Olarak Olmesartan - TurkHipertansiyon · Bir ARB Olarak Olmesartan ... (Prevalence,...
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Bir ARB Olarak Olmesartan
Prof. Dr. Tevfik Ecder İstanbul Bilim Üniversitesi Tıp Fakültesi
İç Hastalıkları Anabilim Dalı Nefroloji Bilim Dalı
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PatenT (Prevalence, awareness, treatment and control of hypertension in Turkey)
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Direkt vazodilatörler
Alfa- blokerler
Periferik sempatolitikler
Ganglion blokerleri
Veratrum alkaloidleri
Santral 2 agonistleri
Kalsiyum antagonistleri-
non-DHP’ler
Beta-blokerler
Tiyazid diüretikler
Kalsiyum antagonistleri
-DHP’ler
ARB’ler
1940 1950 1957 1960 1970 1980 1990 2000
ACE inhibitörleri
Etki ve tolerabilite
Antihipertansif İlaçlar
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Antihipertansif Tedaviye Uyum
Bloom BS, et al. Clin Ther 1998;20:671-681
3843
50
5864
0
10
20
30
40
50
60
70
Diüretik Beta-bloker Kalsiyum kanal
blokeri
ACE inhibitörü ARB
* p<0.007 (ACE inhibitörüne göre)
* %
1. Yılın Sonunda
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H3CH2CH2C
N
N
CH2
CH3
O
O O
N
N
N N H
C H3C CH3
OH
COCH2
O
H3CH2CH2C
N
N
CH2
N
N
N N H
C H3C CH3
OH
Olmesartan Medoksomil Olmesartan
Barsak duvarında de-esterifikasyon
Schwocho LR, Masonson HN. J Clin Pharmacol. 2001;41:515-527.
Olmesartan Medoksomil
COOH
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Olmesartan Losartan Kandesartan
İrbesartan Telmisartan Eprosartan Valsartan
Fekal atılım (%)
50-65 60 67 80 98 90 83
Üriner atılım (%)
35-50 35 33 20 <1 7 13
CYP450 metabolizması
Hayır Evet
CYP 3A4
Hayır Evet
CYP 2C9
Hayır Hayır Hayır
İlaç etkileşimleri
Hayır Rifampin, flukonazol
Hayır Hayır Digoksin Hayır Hayır
Gıdanın etkisi
( AUC%)
Yok 10 Yok Yok 6-20 25 40-50
Doz sıklığı
( / gün)
1 kez 1-2 kez
1-2 kez 1 kez 1 kez 1-2 kez 1 kez
Anjiyotensin Reseptör Blokerleri
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Malacco et al: J Hypertens 28: 2342-2350, 2010
n=549
n=553
Ramipril 2.5 mg
Ramipril 5 mg
Ramipril 10 mg
Olmesartan 40 mg
Olmesartan 10 mg
Olmesartan 20 mg
ABPM ABPM 12. hafta Başlangıç 2. Hafta 6 Hafta -2. Hafta
Plasebo
Açık etiketli tedavi
n=542
n=539
Evre 1- 2 HT hastalar,
65-89 yaş (ort 72 yaş)
n=1102
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-6
-10
-12
-14
-8
Olmesartan Ramipril
1-6 saat
n= 630 *p<0.05 **p< 0.01
Sis
toli
k K
an
Bas
ınc
ınd
a A
za
lma
(m
mH
g)
-4 7-12 saat 13-18 saat 19-24 saat
12 haftalık olmesartan ve ramipril tedavisiyle ABPM kayıtları
*
**
KB < 140/90 mmHg
Malacco et al: J Hypertens 28: 2342-2350, 2010
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Malacco et al: J Hypertens 28: 2342-2350, 2010
-15
-20
-10
2. Hafta
n= 735
*p<0.05 **p< 0.01
Sis
toli
k K
an
Bas
ınc
ınd
a A
za
lma
(m
mH
g)
-5
KB < 140/90 mmHg
6. Hafta 12. Hafta
12 haftalık olmesartan ve ramipril tedavisiyle ABPM kayıtları
*
*
**
Olmesartan
Ramipril
Metabolik Sendromlu Yaşlı Hipertansifler
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Kario et al: Journal of Human Hypertension 1-8, 2013
HONEST (The Home BP measurement with Olmesartan Naive patients to Establish Standard Target blood pressure study)
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Kario et al: Journal of Human Hypertension 1-8, 2013
HONEST (The Home BP measurement with Olmesartan Naive patients to Establish Standard Target blood pressure study)
P<0.0001 (Tedavi öncesine göre)
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Kario et al: Journal of Human Hypertension 1-8, 2013
HONEST (The Home BP measurement with Olmesartan Naive patients to Establish Standard Target blood pressure study)
P<0.0001 (Tedavi öncesine göre)
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Kario et al: Journal of Human Hypertension 1-8, 2013
HONEST (The Home BP measurement with Olmesartan Naive patients to Establish Standard Target blood pressure study)
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Kario et al: Journal of Human Hypertension 1-8, 2013
HONEST (The Home BP measurement with Olmesartan Naive patients to Establish Standard Target blood pressure study)
Diyabetik Hastalar (n=3879)
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Kario et al: Journal of Human Hypertension 1-8, 2013
HONEST (The Home BP measurement with Olmesartan Naive patients to Establish Standard Target blood pressure study)
Kronik Böbrek Hastaları (n=3863)
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Randomize, çift kör, çok merkezli çalışma
Hipertansiyonu olan (140-180 / 90-105 mm Hg) 165 hasta
Olmesartan (20-40 mg/gün) ile atenolol (50-100 mg/gün) tedavilerinin karotis intima-media kalınlığı ve plak hacmi üzerine olan etkilerinin karşılaştırılması
Takip süresi: 2 yıl
MORE (The Multicentre Olmesartan Atherosclerosis Regression Evaluation Study)
Stumpe et al: Therapeutic Advances in Cardiovascular Disease 1:97-106, 2007
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MORE (The Multicentre Olmesartan Atherosclerosis Regression Evaluation Study)
Stumpe et al: Therapeutic Advances in Cardiovascular Disease 1:97-106, 2007
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OLIVIUS (Impact of Olmesartan on progression of coronary atherosclerosis:
evaluation by IntraVascular UltraSound)
Hirohata et al: J Am Coll Cardiol 55: 976-982, 2010
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Hirohata et al: J Am Coll Cardiol 55: 976-982, 2010
OLIVIUS (Impact of Olmesartan on progression of coronary atherosclerosis:
evaluation by IntraVascular UltraSound)
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Hirohata et al: J Am Coll Cardiol 55: 976-982, 2010
OLIVIUS (Impact of Olmesartan on progression of coronary atherosclerosis:
evaluation by IntraVascular UltraSound)
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Hirohata et al: J Am Coll Cardiol 55: 976-982, 2010
PAV (Percent atheroma volume)
OLIVIUS (Impact of Olmesartan on progression of coronary atherosclerosis:
evaluation by IntraVascular UltraSound)
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OLIVIUS-Ex (Impact of Olmesartan on progression of coronary atherosclerosis:
evaluation by IntraVascular UltraSound Extension trial)
Hirohata et al: Atherosclerosis 220: 134-138, 2012
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Hirohata et al: Atherosclerosis 220: 134-138, 2012
Olaysız* Sağkalım
*Kardiyovasküler veya serebrovasküler nedenlere bağlı ölüm, miyokard infarktüsü, inme, angina veya kalp/böbrek yetersizliği
OLIVIUS-Ex (Impact of Olmesartan on progression of coronary atherosclerosis:
evaluation by IntraVascular UltraSound Extension trial)
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ROADMAP (Randomized Olmesartan And Diabetes MicroAlbuminuria Prevention)
Tip 2 Diyabeti ve Normoalbüminürisi Olan 4447 Hasta Primer sonlanım noktası: Mikroalbüminüri gelişimi
Haller et al: N Engl J Med 364: 907-917, 2011
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Kardiyo/ Serebro vasküler
Ölüm
Son Dönem Kalp Hastalığı/ Beyin Hasarı ve
Demans
Son Dönem Böbrek
Yetersizliği
Endotel Disfonksiyonu
Mikro- albüminüri
Konjestif Kalp Yetersizliği/
Sekonder İnme
Nefrotik Proteinüri
Dzau, Braunwald. Am Heart J 121:1244–1263, 1991
Myokard İnfarktüsü ve İnme
Ateroskleroz ve Sol Ventrikül
Hipertrofisi
Ventrikül Dilatasyonu/
Kognitif Disfonksiyon
Yeniden Şekillenme
Hipertansiyon, Risk Faktörleri Diyabet, Obezite, Yaşlılık
Makro- albüminüri
Endotel Disfonksiyonu
Kardiyorenal Süreç
Losartan (RENAAL) İrbesartan
(IDNT)
İrbesartan (IRMA 2) Valsartan (MARVAL)
Olmesartan (ROADMAP)
Valsartan (VAL-HeFT)
Kandesartan (CHARM)
Eprosartan (MOSES)
Valsartan (VALIANT)
Losartan (LIFE)
Telmisartan (ONTARGET)
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2013 ESH/ESC Guidelines for the Management of Arterial Hypertension
Özel Durumlarda Tercih Edilecek İlaçlar
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2011
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2014 Guideline for the Management of High Blood Pressure in Adults (JNC 8)
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Journal of Hypertension 32: 3 – 15, 2014
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