All concepts, explanations, trials, and studies have been
re-written in plain English and may contain errors. I am
not a doctor
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Valsartan is a highly selective blocker of receptors for
angiotensin type 1 (AT1). Studies show that valsartan
eases the effects of angiotensin 2 like constricted blood
vessels, excess cell growth, and aldosterone release.
	Valsartan is rapidly absorbed with
maximum blood level one to two hours after taking it.
Half-life is about 8 hours and most of the drug is
excreted in the stool.
	No dose adjustment is needed for patients
with weak kidneys (creatinine clearance over 10 ml/
min). Dose should not be more than 80 mg daily in
patients with weak liver function. Valsartan should
not be used in patients with severe liver dysfunction.
	No important drug interactions have yet
been seen. Valsartan reduces blood pressure. Starting
dose is 80 mg once daily. If required, the dose may
either be increased to 160 mg once daily or hydro-
chlorothiazide may be added.

Title:     Valsartan: a novel angiotensin type 1 receptor
             antagonist.
Author: Thurmann PA.
Source:  Expert Opin Pharmacother 2000 Jan;1(2):337-50.
PMID:  11249553.
=========================

Quality of life is measured in trials using questionnaires.
Disease progression is measured by tracking mortality
and hospitalizations. We need intermediate markers for
progression of heart disease that can be substituted for
hospitalizations and mortality. This will improve
effectiveness and shorten follow-up of clinical trials.
	In CHF, multiple meds are required to get
best improvement in quality and length of life. Some
drugs may improve one endpoint and worsen another.
For example, beta-blockers may cause short-term ill
effects on quality of life but may slow disease progression.
Some inotropic drugs reduce symptoms but shorten life
expectancy.
	Val-HeFT (Valsartan in Heart Failure Trial)
will test the effectiveness and safety of the ARB valsartan
in combination with ACE inhibitors and all other
standard CHF drugs. The study is set up to detect a
mortality benefit and should establish the role of ARBs
in CHF. When this trial and other ongoing studies are
done, we will be more able to define the role of ARBs
in CHF treatment.

Title:      Improving outcomes in congestive heart failure:
             Val-HeFT. Valsartan in Heart Failure Trial.
Author: Cohn, JN.
Source:  Cardiology 1999;91 Suppl 1:19-22.
PMID:  10449891
=========================

Val-HeFT (Valsartan Heart Failure Trial) is the first
large trial to study the ARB valsartan added to all
other standard meds in CHFers.
	A total of 5,010 patients with EF under
40% took either 160 mg valsartan twice a day or
placebo. The study patients are average age of 63
years and are 80% male, 90% white, 7% black, and
3% Asian. Previous coronary heart disease is
known in 57%. ACE inhibitors are taken by 93%,
diuretics by 86%, digoxin by 67%, and beta-blockers
by 36%. Patients had class 2 to class 4 HF.
	Valsartan was started at 40mg twice a
day and then raised to 160mg twice a day.
	Primary endpoints were all-cause death
or a combined endpoint of all-cause mortality, HF
hospitalization, and worsening CHF requiring
inotropic or vasodilating agents.
	Compared to placebo, valsartan reduced
the combined mortality/complications endpoint by
13% and hospitalization for heart failure by 28%,
although all-cause mortality was not significantly
reduced.

Title:       Baseline demographics of the Valsartan Heart
               Failure Trial. Val-HeFT Investigators.
Authors: Cohn JN, Tognoni G, Glazer R, Spormann D.
Source:   Eur J Heart Fail 2000 Dec;2(4):439-46.
PMID:   11113722.

Title:      The Role of Angiotensin II Receptor Blockers
               in the Treatment of Heart Failure Patients.
Authors: Michael Theal, Catherine Demers, Robert S.
               McKelvie.
Source:   CHF 9(1):29-34, 2003.
=========================

Many short-term studies have now compared ACE
inhibitors to ARBs. Most have focused on endpoints
such as blood pressure, kidney function, or cough.
These studies have generally shown that ARBs cause
fewer side efffects but otherwise the 2 drug classes
have similar effectiveness.
	The largest completed trial comparing
ARBs to ACE inhibitors is ELITE 2 (Evaluation of
Losartan in the Elderly). ELITE 2 did not confirm the
results of a smaller study - it did not show improvement
in death or hospitalization for CHF with ARB use
alone. Many longer-term studies are under way, but
most will compare the combination against an ACE
inhibitor alone.


Title:     Therapeutic trials comparing angiotensin
             converting enzyme inhibitors and angiotensin
             II receptor blockers.
Author: Elliott WJ.
Source:  Curr Hypertens Rep 2000 Aug;2(4):402-11.
PMID:  10981176.