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IRBESARTAN IN THE TREATMENT OF
HEART FAILURE
IRBESARTAN
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What is Irbesartan?
Irbesartan is a selective nonpeptide antagonist of angiotensin II
type 1 receptor (AT1). Irbesartan
inhibits the action of angiotensin II,
which acts through the binding to
the AT1 receptor.
Indicated for the treatment of
hypertension
Irbesartan may also delay
progression of diabetic nephropathy
Also indicated for the reduction of
renal disease progression in patients
with type 2 diabetes, hypertension
and microalbuminuria (>30 mg/24
hours) or proteinuria (>900 mg/24
hours).
It has also been shown in the
treatment of heart failure.
IRBESARTAN
ROLE PLAYED BY THE ACTIVATION OF AT1
RECEPTORS
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Activation of AT1 receptors
plays the crucial role in the
development of:
Hypertension
Left ventricular hypertrophy
Progression of lipid disorders
Impairment of renal function
Therefore, angiotensin II type
1 receptor antagonists could
be used as a new therapeutic
option in treatment of
hypertension which may lead
to complications such as
Hypertensive
cardiomyopathy( Heart
failure due to chronically high
blood pressure).
CAUSES OF HEART FAILURE
•Left
sided:
•Hypertension (high blood
pressure), aortic and mitral
valve disease aortic
coarctation.
•Right
sided:
•Pulmonary hypertension
(primary pulmonary arterial
hypertension versus hypoxic
vasoconstriction and capillary
destruction due to chronic
lung disease) pulmonary and
tricuspid valve disease.
ACTIONS OF AT 1 ANTAGONISTS
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Vasoconstriction
Central and peripheral
sympathetic stimulation
Release of aldosterone
and adrenaline from
adrenals
Renal actions promoting
salt and water
reabsorptions
Central actions like
thirst
Vasopressin release
Growth promoting
actions on heart and
blood vessels
ADVANTAGES OF AT 1 ANTAGONISTS
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Oral bioavailability of
this AT1 antagonist is
relatively high.
long lasting blood
pressure lowering
action
possibility of taking it
once a day
REASONS WHY IRBESARTAN (ANGIOTENSIN
ANTAGONIST) IS USED OVER ACE INHIBITORS
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They do not interfere with degradation of bradykinin
They result in more complete inhibition of AT 1 receptor activation
They result in indirect AT II receptor activation . Due to blockade of AT1
receptor mediated feedback inhibition- more A II is produced which acts on AT
2 receptor that remains unblocked. ACE inhibitors result in depression of both
AT 1 and AT 2 activation. Activation of the renin-angiotensin system in patients
with heart failure causes vasoconstriction and retention of sodium and water.
Despite the known benefits of ACE inhibitors and, more recently, betaadrenergic blocking agents, morbidity and mortality remain unacceptably high in
patients treated with ACE inhibitors.
AT1 receptor antagonists represent an alternative therapy that may provide
more complete blockade of an activated renin-angiotensin system while avoiding
some of the detrimental side effects of ACE inhibitors
Irbesartan is a new, highly selective nonpeptide antagonist of AT1 receptors
with pharmacokinetic properties that favor once-per-day dosing
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HAEMODYNAMIC EFFECTS OF IRBESARTAN
Reduction of:
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Pulmonary Capilary Wedge Pressure(PCWP)
• Mean pulmonary arterial pressure (MPAP)
• Mean systemic arterial pressure (MSAP)
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No dose related effect on heart rate
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Slight increase in Cardiac Index after 12 weeks of
administration of irbesartan
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Tendency for LVEF to increase as a function of
dose of irbesartan
THE PHARMACOKINETIC AND PHARMACODYNAMIC OF
IRBESARTAN IN HEART FAILURE
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Mainly through oral and i.v.
administration, the
pharmacokinetics of
irbesartan indicates that
there is little influence of
potential changes in
organ/tissue perfusion and
gut edema on the absorption,
distribution, and elimination
of irbesartan.
Pharmacodynamic parameters
cannot be judged
Therefore no dosage
adjustments are needed
SAFETY AND TOLERABILITY OF IRBESARTAN
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Irbesartan was generally well-tolerated in
patients with mild-to-severe heart failure.
Discontinuation of medication and adverse
events are not related to dose of
irbesartan.
CONCLUSION
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Once-daily administration of Irbesartan 75 mg or
150 mg to patients with symptomatic heart failure
and LVEF ≤40% is well-tolerated
Resulting in sustained haemodynamic improvement
and prevents worsening of heart failure.
Irbesartan appears to be a promising new therapy
for patients with chronic heart failure.
SEARCH STRATAGIES
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KEYWORDS USED ARE:
“Irbesartan”
“Heart Failure”
DATABASES AND SEARCH TOOLS
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Abstract database : Pubmed,Sciencedirect
Free full-text database: Pubmed ( linked
to ScienceDirect)
SEARCH PROCESS
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Abstract Database:
Pubmed: Use Pubmed basic search. Use search MeSH =”Heart
failure” and found 49 results. I selected the first result and
narrowed the search to major subheadings, namely:
Drug therapy and Therapy
I restricted the search to these subheadings and combined
another search term “irbesartan” by selecting the option Send to
Search Box with AND, and searched
PubMed.=("HeartFailure/drugtherapy"[Majr] OR "Heart
Failure/therapy"[Majr])AND "Irbesartan"[All fields]
I got 27 results in all, out of which 3 are free full text and 10
are from Southern Medical University Library. I referred to these
10 articles from Southern Medical University Library and 2 from
all the results.
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2.Sciencedirect: Use Sciencedirect advanced
search. I typed “Heart failure” in AbstractTitle-Key AND “Irbesartan” in Title and
clicked search . I got 14 results which I
referred for my topic
BROWSING THE SEARCH RESULTS AND WRITING
THE MOST RELATED CITATIONS
PUBMED:
1. Related Articles, Links
Zukowska-Szczechowska E, Gosek K, Grzeszczak W.
[Irbesartan--antihypertensive treatment in patients with heart failure and diabetes mellitus]
Przegl Lek. 2002; 59(3):160-4. Review. Polish.
PMID: 12184030 [PubMed - indexed for MEDLINE]
2. Related Articles, Links
Kostis JB, Vachharajani NN, Hadjilambris OW, Kollia GD, Palmisano M, Marino MR.
The pharmacokinetics and pharmacodynamics of irbesartan in heart failure.
J Clin Pharmacol. 2001 Sep; 41(9):935-42.
PMID: 11549097 [PubMed - indexed for MEDLINE]
3. Related Articles, Links
Carson P, Massie BM, McKelvie R, McMurray J, Komajda M, Zile M, Ptaszynska A, Frangin G; for the I-PRESERVE
Investigators.
The irbesartan in heart failure with preserved systolic function (I-PRESERVE) trial: rationale and design.
J Card Fail. 2005 Oct; 11(8):576-85.
PMID: 16230259 [PubMed - indexed for MEDLINE]
4. Related Articles, Links
Havranek EP, Thomas I, Smith WB, Ponce GA, Bilsker M, Munger MA, Wolf RA.
Dose-related beneficial long-term hemodynamic and clinical efficacy of irbesartan in heart failure.
J Am Coll Cardiol. 1999 Apr; 33(5):1174-81.
PMID: 10193713 [PubMed - indexed for MEDLINE]
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SCIENCEDIRECT:
5. Predictors of outcome in heart failure with preserved ejection fraction: one year findings rom
the Irbesartan in Heart Failure With Preserved Systolic Function Trial (I-PRESERVE)
European Journal of Heart Failure Supplements, Volume 7, Supplement 1, June 2008, Page 87
P.E. Carson, M. Komajda, R. Mckelvie, J. McMurray, M. Zile, A.A. Ptaszynska, M. Donovan, B. Massie
6. Diabetes is associated with increased risk of CV events in heart failure with preserved ejection
fraction: findings from the Irbesartan in Heart Failure with Preserved Systolic Function Trial
European Journal of Heart Failure Supplements, Volume 7, Supplement 1, June 2008, Page 2
R.S. Mckelvie, M. Komajda, B.M. Massie, J.J. McMurray, M.R. Zile, M. Donovan, A. Ptaszynska, P.
Carson
7. The Baseline Characteristics of Patients Enrolled in the Irbesartan in Heart Failure with
Preserved Systolic Function Trial Are Similar to Those in the Community but Differ from CHARMPreserved
Journal of Cardiac Failure, Volume 12, Issue 6, Supplement 1, August 2006, Page S77
Barry Massie, Peter Carson, Michel Komajda, Robert McKelvie, John McMurray, Michael Zile, Gerald
Frangin, Agata Ptaszynska
8. Comparison of angiotensin-converting enzyme inhibitor alone and in combination with
irbesartan for the treatment of heart failure
International Journal of Cardiology, Volume 125, Issue 1, 28 March 2008, Pages 16-21
Leo Chi-Chiu Kum, Gabriel Wai-Kwok Yip, Pui-Wai Lee, Yat-Yin Lam, Eugene B. Wu, Anna Kin-Yin Chan,
Jeffrey Wing-Hong Fung, Joseph Yat-Sun Chan, Qing Zhang, Shun-Ling Kong, Cheuk-Man Yu
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9. The Irbesartan in Heart Failure With Preserved Systolic Function (I-PRESERVE) Trial: Rationale and Design
Journal of Cardiac Failure, Volume 11, Issue 8, October 2005, Pages 576-585
Peter Carson, Barry M. Massie, Robert McKelvie, John McMurray, Michel Komajda, Michael Zile, Agata Ptaszynska, Gerald
Frangin and for the I-PRESERVE Investigators
10. Effects of angiotensin-converting enzyme inhibitor plus irbesartan on maximal and submaximal exercise capacity
and neurohumoral activation in patients with congestive heart failure
American Heart Journal, Volume 149, Issue 5, May 2005, Page 938
Martine Blanchet, Richard Sheppard, Normand Racine, Anique Ducharme, Daniel Curnier, Jean-Claude Tardif, Pierre Sirois,
Marie-Catherine Lamoureux, Jacques De Champlain, Michel White
11. Synergistic efficacy of irbesartan and benazepril on exercise performance and oxygen consumption at peak
exercise in hypertensives with congestive heart failure
American Journal of Hypertension, Volume 17, Issue 5, Supplement 1, May 2004, Page S165
Maria Leonarda De Rosa, Orazio Viola, Michele Polimeno, Massimo Chiariello
12. 1012-129 Dual angiotensin-II suppression with angiotensin-converting enzyme inhibitor and irbesartan improves
submaximal exercise time without changes in exercise-induced neurohumoral response in patients with congestive
heart failure
Journal of the American College of Cardiology, Volume 43, Issue 5, Supplement 1, 3 March 2004, Page A159
Martine Blanchet, Richard Sheppard, Daniel Curnier, Jacques de Champlain, Pierre Sirois, Hélène Créo, André Roof, Lucette
Whittom, Jean-Claude Tardif, Anique Ducharme, Normand Racine, Michel White
13. A multicenter, randomized, double-blind study of the antihypertensive efficacy and tolerability of irbesartan in
patients aged ≥65 years with mild to moderate hypertension
Clinical Therapeutics, Volume 22, Issue 10, October 2000, Pages 1213-1224
Yves Lacourcière
14. Dose-related beneficial long-term hemodynamic and clinical efficacy of irbesartan in heart failure : Havranek EP,
Thomas I, Smith WB, et al: J Am Coll Cardiol 33: 1174–1181,1999
Journal of Cardiothoracic and Vascular Anesthesia, Volume 13, Issue 5, October 1999, Page 642
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15. Dose-related beneficial long-term hemodynamic and clinical efficacy of
irbesartan in heart failure
Journal of the American College of Cardiology, Volume 33, Issue 5, April 1999, Pages
1174-1181
Edward P. Havranek, Ignatius Thomas, William B. Smith, George A. Ponce, Martin Bilsker,
Mark A. Munger, Robert A. Wolf, for the Irbesartan Heart Failure Group
16. Irbesartan decreases atrial natriuretic peptide levels and improves ejection
fraction in diabetic patients with congestive heart failure
Journal of Cardiac Failure, Volume 4, Issue 3, Supplement 1, September 1998, Page 48
Donald S. Chang, Linda G. Tan, Stanley A. Tan
17. Irbesartan compared with lisinopril in patients with mild to moderate heart failure
Journal of the American College of Cardiology, Volume 31, Supplement 1, 1998, Page 68
N. Vijay, I. A. Alhaddad, D. Marty Denny, D. Ruff, M. Yasin, L. Yellen, S. Lyver, C. Bryson,
C. -S. Lin, R. A. Wolf
18. Irbesartan combined with conventional therapy, including angiotensin converting
enzyme inhibitors, in heart failure
Journal of the American College of Cardiology, Volume 31, Supplement 1, 1998, Page 188
M. Tonkon, N. Awan, I. Niazi, P. Hanley, L. Baruch, C. -S. Lin, D. Costagliola, G. Cucinotta,
R. A. Wolf, A. J. Block
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