Escolar Documentos
Profissional Documentos
Cultura Documentos
1
RAAS overview
ARB overview
Indications
Contraindications
Drug information
ACEI and ARB differences
ARB in Type 2 Diabetic Nephropathy
ARB in CV disorders
Conclusion
References
2
3
ANGIOTENSIN II - SUPPORT OF THE BLOOD PRESSURE
↑ Cardiac Aldosterone
Contractility Angiotensin Secretion
II
Sympathetic ↑ Thirst
Facilitation:
ADH Release
Central
Nerve terminal
(ganglionic ?)
All known physiologic effects are mediated
by the angiotensin II type 1 receptor
4
Angiotensin receptor blockers block receptors that
angiotensin II binds to, particularly angiotensin II type 1
receptors.
5
Mechanism of Action
6
Indication Hypertension Diabetic LV
Nephropathy Hypertroph
y
Valsartan (x)
Telmisartan (x)
7
Valsartan Telmisartan Losartan Irbesartan
8
ADEC Category D
9
Circulating and intrarenal angiotensin II constricts efferent arteriole
more than afferent arteriole within the kidney, which helps to maintain
glomerular capillary pressure and filtration.
10
Well tolerated
Fatigue
Headache
11
Losartan + Ketoconazole
◦ Due to inhibition of formation of losartan active metabolite.
Losartan + rifampicin
◦ Due to increased losartan metabolism, decreasing concentration and
affecting BP control
12
(1) Angiotensin converting enzyme (ACE) is a kininase.
This explains why less cough side effects are seen with
Angiotensin receptor blockers.
13
(2) ACE inhibitors, by decreasing angiotensin II production,
reduce the effect of both AT1 and AT2 receptors
14
(3) In the heart, brain, and perhaps the blood vessels, the
production of angiotensin II may be catalyzed by enzymes
other than angiotensin converting enzyme, such as chymase.
15
Proven efficacy
◦ Two major trials have demonstrated a clear benefit in terms of
renoprotection with ARBs in patients with nephropathy due to type 2
diabetes.
16
In the RENAAL trial..
◦ comparison between losartan (50mg titrating to 100mg) and placebo
was done
17
ARB in Type 2 Diabetes and
Nephropathy Summary
www.hypertensiononline.org
18
Primary Endpoint: Average
Composite of doubling of Duration
serum creatinine, end stage
renal disease, or death
Irbesartan 150-300 mg
vs Amlodipine* ↓ 23% (p=0.006)
20
VALIANT
◦ comparison between Valsartan and Captopril.
◦ Patients were at high risk of cardiovascular events and were post-MI.
◦ Similar efficacy.
Val-HeFT
◦ Comparison between Valsartan and placebo
◦ Summary:
◦ Diovan reduced endpoint mortality and HF morbidity
◦ Reduced HF hospitalisations, reversed LV remodelling
◦ Improved HF signs and symptoms.
21
Subgroup without ACE inhibitor background
therapy
1.000
0.914
Event-free probability
DIOVAN (n=185)
0.829
0.743
0.657 44%
risk
0.571 reduction*
0.486 Placebo
0 (n=181)
0 3 6 9 12 15 18 21 24 27
Time since randomisation (months)
*p<0.001 for morbidity/mortality; 33% relative risk (RR; p=0.017) for
all-cause mortality
Val-HeFT: Valsartan in Heart Failure Trial
Maggioni et al. J Am Coll Cardiol 2002;40:1414–21
22
Patients aged 55–80 years with BP 160–200/95–115 mmHg and LVH
Treatment titrated to <140/90 mmHg
4.8 years of follow-up
30 13% risk reduction*
27.9
(p=0.021)
events per 1,000 patient-
23.8
Death, MI and stroke
20
10
years
0 Atenolol-based Losartan-based
(n=4,588) (n=4,605)
BP at end of study: 145/81 mmHg 144/81 mmHg
*RR 0.87, 95% CI: 0.77–0.98
LVH = left ventricular hypertrophy
LIFE = Losartan Intervention For Endpoint Dahlöf et al. Lancet 2002;359:995–100323
ARBs are primarily known for their antihypertensive action
but there is much about what they can do which is still
being investigated.
24
(1) Wong, M, Staszewsky, L, Latini, R, et al. Valsartan benefits left ventricular
structure and function in heart failure: Val-HeFT echocardiographic study. J Am
Coll Cardiol 2002; 40:970.
(2) Fogari et.al. A Double Blind Crossover Study of Antihypertensive Efficacy of
Angiotensin II Antagonists and their Activation of The Renin-Angiotensin
System. 2000; 61:10
(3) Chobanian, AV, Bakris, GL, Black, HR, et al. The Seventh Report of the Joint
National Committee on Prevention, Detection, Evaluation, and Treatment of
High Blood Pressure: The JNC 7 Report. JAMA 2003; 289:2560
(4) Cohn, JN, Tognoni, G. Valsartan Heart Failure Trial Investigators. A
Randomized Trial of the Angiotensin-Receptor Blocker Valsartan in Chronic
Heart Failure. N Engl J Med 2001; 345:1667.
(5) Pitt, B, Poole-Wilson, PA, Segal, R, et al. Effect of Losartan Compared With
Captopril on Mortality in Patients With Symptomatic Heart Failure: Randomised
Trial - The Losartan Heart Failure Survival Study ELITE II. Lancet, 2000,
355:1582.
(6) Brenner BM, Cooper ME, de Zeeuw D, Keane WK, Mitch WE, Parving HH,
Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S, et al.: Effects of losartan on
renal ands cardiovascular outcomes in patients with type 2 diabetes
and nephropathy. N Engl J Med 2001, 345:861-869.
(7) UptoDate
(8)
25
26