ARBs (Angiotensin receptor blockers) are the most widely used anti hypertensive throughout the world. A solid knowledge related to ARB will make our practice more patients friendly & benefit will be maximum.

1. Presenter
Dr. Md. Arifur Rahman
MD (Cardiology)
Registrar, Cardiology
National Institute of Cardiovascular Diseases
Role of ARB
Hypertension
in the management of

2. History of Hypertension
1931- “It is an important
compensatory mechanism
which should not be
tampered with.”

3. 2011
Azilsartan,
latest ARB ,USFDA

4. Why HTN getting
so much importance?

5. Global Mortality 2010:
Hypertension is the major risk factor
Adapted from Ezzati et al. Lancet 2012;360:1347-1360.
Attributable mortality in millions (total: 55 861 000)
Developing regions
Developed regions
0 87654321
7.6 million deaths

9. Beta-blockers
Lost its glorious past
 Beta-blockers appear to be worse for total mortality
and CV events, stroke and CHD.
 Lesser ability to reduce central SBP and pulse
pressure.
 Less effective in regressing or delaying OD,
 Increase body weight and
 Facilitate new-onset diabetes in predisposed patients.

11. MS in prescriptions
Canada, United States, Austria, Belgium, Czech Republic, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Netherlands, Poland, Portugal,
Slovakia, Spain, Switzerland, United Kingdom, Australia, Egypt, Indonesia, Japan (includes hospital data), New Zealand, Pakistan, Philippines, Saudi
Arabia, South Africa, Thailand, Turkey, Argentina, Brazil, Colombia, Mexico, Venezuela.
RAAS inhibitors are the cornerstone
of the antihypertensive treatment
Source: IMS. Medical Universe - MAT in prescriptions, 35 countries,
2009
ACEi plain + combCCB
31%
DIU
10%
BB
12%
ARB plain + comb
RAAS
inhibitors
47%

12. RAAS Modulators
1.Angiotensin Converting Enzyme
Inhibitors
• Ramipril
• Enalapril
• Lisinopril
• Perindopril
2. Angiotensin Receptor Blockers
• Losartan
• Valsartan
• Candesartan
• Telmisartan
• Irbesartan
• Olmesartan
• Azilsartan
3.Direct Renin Inhibitors
• Aliskerin

13. Development of ARB’s
Losarta
n
1986
Valsartan,
Candesart
an
Irbesartan
1990
Telmisart
an
1991 Olmesartan1995 Azilsatan2011
Became the
first
successful
Ang II
antagonist
drug
Valsartan –
nonheterocyclic ARB
Candesartan –
Prodrug have stronger
blood pressure
lowering effects than
and losartan.
Irebesartan - longer
acting than valsartan
& losartan
Telmisartan -
longest
elimination
half-life of the
ARBs or about
24 hours
Olmesartan -
Newert ARB
on the market,
marketed in
2002
Azilsartan -
Newest ARB
on the market,
FDA approved
2011

14. Drug comparison and pharmacokinetics
1. Sankyo Pharma Inc (US). Expanding the Paradigm for Hypertension Management with a New Angiotensin II Receptor Blocker. Benicar® (Olmesartan
Medoxomil) [product monograph]. New York: Advantage Communications, 2002.
2. Olin BR, ed. Drug Facts and Comparisons. St. Louis: JB Lippincott Co, 2002:514–518.14
Azilsartan Yes 60 No 11 -- >99 -- 55 45

15. Key trends in ARB
Losartan lower the chance of stroke.
reduce serum uric acid levels.
treating nephropathy in patients withT2DM
Valsartan First ARB to receive approval in Heart Failure
Reverses ventricular remodeling and Improves survival outcome in HF
Telmisartan Highly selective inhibition of the angiotensin II receptor 1 (AT1)
longest plasma half-life, largest volume of distribution
Olmesartan Significant mean blood pressure reduction
Azilsartan Highly selective inhibition of the angiotensin II receptor 1 (AT1)
longer plasma half-life, larger volume of distribution
Powerful 24-hour action, curbing the morning surge in blood pressure
compared to other leading ARB’s

16. ARB in Reducing BP and CV events
Name Patient
population
Drugs/follow
up
Results
LIFE
(Losartan
Intervention For
Endpoint
Reduction in
Hypertension
Study)
9,193 patients
aged 55-80 yr
with
hypertension
and LVH
Losartan, 50-
100 mg qd, vs
atenolol, 50-
100 mg qd
Mean follow-
up: 4.8 yr
Losartan decreased the
composite end point
(cardiovascular mortality,
MI, and stroke)
significantly more than
atenolol for a similar
reduction in blood pressure
OPTIMAAL
(Optimal Trial In
Myocardial
Infarction with
the Angiotensin
Receptor
Blocker
Losartan)
5,477
European
patients aged
over 50 with
confirmed
acute MI and
heart failure.
Losartan, 50
mg qd, vs
captopril, 50
mg tid
Mean follow-
up: 2.7 yr
No significant difference in
overall mortality between
the groups. The ARB was
better tolerated than the
ACE inhibitor, with
significantly fewer
withdrawals due to adverse
effects.
16

17. Renal Protection in Diabetes with ARBs
RENAAL1
(Reduction of
Endpoints in
NIDDM with
the ARB
Losartan)
1,513 patients
aged 31-70 yr
with type 2
diabetes and
nephropathy
Losartan, 50-100 mg qd,
vs placebo in addition to
'conventional‘
antihypertensives such
as beta blockers
Mean follow-up: 3.4 yr
Losartan reduced the
occurrence of proteinuria,
doubling of serum
creatinine concentration
and end-stage renal
disease by 35%, 25% and
28% respectively.
MARVAL2
(MicroAlbumin
uria Reduction
with
VALsartan)
332 patients
aged 35-75 yr
with type 2
diabetes and
microalbuminuri
a
Valsartan, 80-160
mg/day, vs amlodipine,
5-10 mg/day
Follow-up: 24 wk
Valsartan improved the
urinary albumin excretion
rate significantly more
than amlodipine and
restored normal albumin
excretion in significantly
more patients
1. Brenner BM, Cooper ME, de Zeeuw D et al . Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and
nephropathy. N Engl J Med 2001;345: 861-9. 17

27. Up to 20% increase in serum creatinine may sometimes occur when
antihypertensive therapy—particularly RAS blockers—but this should
not be taken as a sign of progressive renal deterioration.
Ref-Cardiovascular disease and mortality in a community-based cohort with mild renal
insufficiency. Kidney Int 2009;56:2214–2219.
RAS blocker and Renal function

28. CKD is classified according to eGFR,
Calculated by
 Modification of diet in renal disease’ (MDRD) formula
 Cockcroft-Gault formula
 CKD EPI demiology Collaboration (CKD-EPI)- require age, sex,
ethnicity and serum creatinine.
These formulae help to detect mild impairment of renal function
when serum creatinine values are still within the normal range.

29. Follow-up
Approximately 4–12 weeks - SBP ≥120 mm Hg, GFR ≥60 mL/min/1.73
m2, change in GFR is <15%, and serum potassium ≤4.5 mEq/L.
 If SBP <120 mm Hg, GFR <60 mL/min/1.73 m2, change in GFR is ≥15%,
or serum potassium >4.5 mEq/L, follow-up measurements should be at
shorter intervals.
In most cases, the ACE inhibitor or ARB should be continued, despite
mild decreases in GFR and increases in serum potassium

30.  The combination of an ACEi with an ARB had some extra blood pressure
lowering but
 had more side effects such as hyperkalemia, hypotension and renal
impairment and did not improve patient outcomes compared to ACEi or
ARB alone.
 Combination reduce urine protein levels but did not reduce cardiovascular
outcomes and did increase adverse renal outcomes such as acute dialysis.
ACEi , ARB combination
ONTARGET:
The ONgoing Telmisartan Alone and in combination with Ramipril
Global Endpoint Trial

31. •In 20 prospective trials, ACEIs were associated with a statistically
significant 13% reduction in all-cause mortality as compared with
control therapy (RR: 0.87, 95%CI: 0.78-0.98, P=0.02).
•ARBs did not give a significant decrease in the risk of major CV
events (RR: 0.94, 95%CI: 0.85-1.01, P=0.07). There were no significant
effects of ARBs on myocardial infarction (RR: 0.89, 95%CI: 0.74-1.07,
P=0.22) or stroke (RR: 1.00, 95%CI: 0.89-1.12, P=0.94).
Ref: ACE inhibitors and ARBs differentially affect CV morbidity and mortality
15-4-2014 • Cheng J et al., JAMA Intern Med. 2014
Impact on all cause mortality of ACE I and ARB

32. The effect of treatment on all-cause mortality was significant with ACE
inhibitors (p = 0.004), but not with ARBs (p = 0.68).
All-cause mortality in ACEI and ARB hypertension trials.

33. Differences in receptor binding between ARBs are reflected in marked
differences in antihypertensive efficacy.
Agents such Telmisartan, Azilsartan, Olmesartan produces a greater
reduction in BP, higher response rate and a longer duration of action.
Due to their good tolerability, less side effects patients compliance is
good resulting better outcome for hypertensive patients.
Take home message