The Roll of ARBs in

Hypertension
Introduction of RAAS…
 There are many important factors that together keep the blood pressure at a
certain level. A central role in maintaining the blood pressure is played by a
chain of key hormonal reactions. The first step in the chain is the production
of renin in the kidneys when the kidneys detect lower blood pressure. The
renin stimulates the formation of a protein called angiotensin I, which is then
converted to angiotensin II by the angiotensin- converting enzyme in the
lungs. Angiotensin II is the most powerful constrictor of blood vessels known.
This effect of constricting blood vessels tends to elevate the blood pressure.
Angiotensin II also causes the secretion of an additional blood pressure
elevating hormone in the adrenal glands, called aldosterone.
 This chain of blood pressure regulating hormones is referred to as the renin-
angiotensin-aldosterone (RAA) hormonal system.
Blocking of RAAS through medicine..

 Several classes of blood pressure lowering (anti-

hypertensive) medications may have some effects
on this hormonal system. However, two classes of
drugs have the most substantial effects on the RAA
system. These two classes are the angiotensin
receptor blockers (ARB drugs) and the angiotensin
converting enzyme inhibitors (ACE inhibitors). Both
of these classes of drugs lower blood pressure by
blocking certain specific steps in the RAA chain.
The mode of action of ARB…

 AT1 Receptor:
Vasoconstriction,
Sympathetic activation,
Cellular growth,
Fibrosis, Thrombosis
 AT2 Receptor:
Vasodilation, Apoptosis,
Inhibition of cellular
growth
For What
Conditions ARBs are Used?

 ARBs are used for controlling high blood pressure,

treating heart failure, and preventing kidney failure in
people with diabetes or high blood pressure. They
may also prevent diabetes and reduce the risk of
stroke in patients with high blood pressure and an
enlarged heart. ARBs may also prevent the
recurrence of atrial fibrillation. Since these
medications have effects that are similar to those of
ACE inhibitors, they often are used when ACE
inhibitors are not tolerated by patients (for example,
due to excessive coughing)
ARBs available in Market !

 Losartan
 Valsartan
 Irbesartan
 Candesartan
 Telmisartan
 Eprosartan
 Olmesartan
Clinical use of Candesartan…

As all angiotensin II receptor antagonists,

candesartan is indicated for the treatment
ofhypertension. Results from the CHARM study in
the early 2000s demonstrated the morbidity
and mortality reduction benefits of candesartan
therapy in congestive heart failure.
Switching From Losartan To Candesartan Achieves
Significant Reductions In Blood Pressure Over 2 Years

Changing from losartan to candesartan achieves significant

reductions in blood pressure over a two-year period
according to a study in the January issue of IJCP,
theInternational Journal of Clinical Practice.

Reference: Evaluation of the clinical outcomes of switching

patients from atorvastatin to simvastatin and losartan to
candesartan in a primary care setting: 2 years on. 
International Journal of Clinical Practice Jan 2008 (1-5). 
Change of medication to candesartan from valsartan is
effective for patients with morning hypertension (ATOM-
Convert C Study) : Candesartan is effective for morning
hypertensive patients

we reported that patients who had taken valsartan demonstrated a particularly large
morning surge, and a significant difference (p = 0.02) was observed compared to that in
those taking candesartan (ATOM study). Methods and Subjects Patients in our outpatient
clinic diagnosed with morning hypertension (over 135/85mmHg), who were already being
treated with valsartan, were changed to candesartan. We estimated, from home blood
pressure, the differences in morning and evening blood pressure values after changing the
medication. Results We investigated 28 morning hypertension patients (men, 14 ; women,
14) who were previously prescribed valsartan, and then changed to candesartan. After
changing to candesartan, systolic blood pressure and diastolic blood pressure recorded in
the outpatient clinic decreased (145.8 ± 13.9mmHg vs. 138.7 ± 13.3mmHg ; 76.7 ±
9.9mmHg vs. 72.8 ± 7.1mmHg, p = 0.0011, p = 0.0230, respectively). Moreover, the
average early morning blood pressure decreased significantly (150.1 ± 10.7mmHg vs.
142.0 ± 14.5mmHg, p = 0.0002). Changes in the differences in blood pressure values
between early morning and evening were largest in patients who changed from valsartan
to candesartan (17.6 ±10.2mmHg vs. 11.9 ± 14.8mmHg, p=0.0120). Conclusion It was
shown that a medication change to candesartan from valsartan is effective in morning
hypertensive patients.
Comparison of effects of losartan, irbesartan,
and candesartanon flow-mediated brachial artery dilation and
on inflammatory and thrombolytic markers in patients with
systemic hypertension

We administered placebo, losartan 100 mg/day, irbesartan 300 mg/day, and

candesartan 16 mg/day during 2 months to 122 patients with mild to moderate
hypertension. Compared with placebo, angiotensin II type-1 receptor blockers
significantly improved the percent flow-mediated dilator response to hyperemia
(p = 0.019 by analysis of variance [ANOVA]) and reduced plasma levels of
malondialdehyde (p = 0.005 by ANOVA). However, only irbesartan and
candesartan therapies significantly lowered plasma levels of plasminogen
activator inhibitor type-1 antigen (p <0.001 by ANOVA) with no differences
between the 2, and only candesartan therapy significantly lowered plasma levels
of monocyte chemoattractant protein-1 (p = 0.004 by ANOVA).

Refrence: American Journal of Cardiology

Volume 93, Issue 11 , Pages 1432-1435, 1 June 2004
Clinical pharmacokinetics of
candesartan.

Candesartan cilexetil is the prodrug of candesartan, an angiotensin II

type 1 (AT1) receptor antagonist. Absorbed candesartan cilexetil is
completely metabolised to candesartan. Oral bioavailability is low (about
40%) because of incomplete absorption. Plasma protein binding in
humans is more than 99%. 
Thanks !