ATACAND is First ARB to Receive Approval for Reducing Both CV Mortality and
Hospitalizations for Heart Failure
WILMINGTON, Del., Feb. 23 /PRNewswire-FirstCall/ -- AstraZeneca today
announced that the US Food and Drug Administration (FDA) has approved its
angiotensin receptor blocker (ARB) ATACAND(R) (candesartan cilexetil) Tablets
for the treatment of heart failure (NYHA class II-IV and ejection fraction
less than or equal to 40%) to reduce the risk of death from cardiovascular
causes and reduce hospitalizations for heart failure. ATACAND is the first
ARB to receive an indication for reducing both cardiovascular mortality and
hospitalizations for heart failure.
The approval was primarily based on results from Candesartan in Heart
Failure Assessment of Reduction in Mortality and morbidity Alternative Trial
(CHARM-Alternative), which examined the effect of ATACAND (n=1013) compared to
placebo (n=1015) in 2,028 heart failure patients who were intolerant to ACE
inhibitors, but were receiving other standard heart failure therapy. The
trial demonstrated that in these CHF patients, the use of ATACAND resulted in
a 23% (p<0.001) relative risk reduction in cardiovascular death or heart
failure hospitalization (406 events in the placebo arm compared to 334 events
in the patients receiving ATACAND), with both components contributing to this
effect.
This finding was supported by a second study of 2,548 subjects
(CHARM-Added) with NYHA Class II-IV heart failure and ejection fraction less
than or equal to 40%, in which subjects were mostly on submaximal doses of ACE
inhibitors. Together, in these studies, patients on ATACAND had a 15% lower
risk of cardiovascular mortality (p=0.005). In these studies, symptoms of
heart failure as assessed by NYHA functional class were also improved
(p<0.001).
The recommended initial dose of ATACAND for the treatment of heart failure
is 4 mg once daily. The target dose is 32 mg once daily, which is achieved by
doubling the dose at approximately two-week intervals, as tolerated by the
patient.
About CHARM Alternative Trial
The CHARM Alternative trial was an international, double-blind, placebo-
controlled, parallel study that evaluated 2,028 patients with symptomatic
heart failure (NYHA Class II-IV) and a left ventricular ejection fraction
(LVEF) less than or equal to 40%, who were intolerant to ACE inhibitors.
They randomly received either ATACAND or a placebo. In most cases, the
starting dose of ATACAND was 4 mg once daily, which was doubled every two
weeks up to the sixth week. Patients received the highest dose tolerated, up
to the target dose of 32 mg once daily. Patients were evaluated at 2, 4, and
6 weeks; at 6 months; and every 4 months after until the end of the trial
(34 months on average). The primary endpoint was time to either
cardiovascular mortality or first hospitalization for heart failure. The
CHARM clinical trial program was sponsored by AstraZeneca.
IMPORTANT SAFETY INFORMATION
PREGNANCY WARNING: When used in pregnancy during the second and third
trimesters, drugs that act directly on the renin-angiotensin system can cause
injury and even death to the developing fetus. When pregnancy is detected,
ATACAND should be discontinued as soon as possible.
In the CHARM program, hypotension was reported in 18.8% of patients on
ATACAND vs. 9.8% of patients on placebo; the incidence of hypotension leading
to drug discontinuation in the candesartan-treated patients was 4.1% compared
with 2.0% in placebo-treated patients. The incidence of abnormal renal
function (e.g., creatinine increase) leading to drug discontinuation in
patients treated with ATACAND was 6.3% vs. 2.9% in placebo-treated patients.
Evaluation of patients with heart failure should always include assessment of
renal function and volume status. The incidence of hyperkalemia was 6.3% in
patients receiving ATACAND vs. 2.1% in those receiving placebo.
The incidence of hyperkalemia leading to drug discontinuation in patients
receiving ATACAND was 2.4% vs. 0.6% in the placebo-treated patients. During
treatment with ATACAND in patients with heart failure, monitoring of blood
pressure, serum creatinine, and serum potassium is recommended during dose
escalation and periodically thereafter.
The adverse event profile of ATACAND in heart failure patients was
consistent with the pharmacology of the drug and the health status of the
patients. In the CHARM program, comparing ATACAND in total daily doses up to
32 mg once daily (n=3803) with placebo (n=3796), 21% of patients receiving
ATACAND discontinued for adverse events vs. 16.1% of placebo patients. For
full Prescribing Information for ATACAND, including boxed WARNING, call
1-800-236-9933 or visit http://www.atacand-us.com.
About Chronic Heart Failure
Heart failure, also called chronic heart failure or CHF, is a condition in
which the heart is unable to pump blood adequately to the rest of the body.
When the heart is not pumping as it should, less oxygen and nutrients are
carried through the body, and some of the wastes may not be removed from the
body. This can result in fatigue, shortness of breath, and fluid buildup in
the lungs, liver, or ankles. It is a serious, progressive, debilitating
condition and frequently leads to a fatal outcome. Many heart failure
patients have impaired left ventricular systolic function and this is the
population that has been studied in most previous heart failure trials. In
these patients, the heart's ability to function as a pump is compromised, as
evidenced by a reduced ejection fraction, which is the percentage of blood
ejected by the heart with each contraction. The normal heart ejects more than
50% of the blood in the left ventricle with each beat. Common causes of heart
failure include coronary artery disease, heart attacks (or myocardial
infarction), high blood pressure (or hypertension), and heart disease of
unknown origin (or cardiomyopathy).
The American Heart Association estimates that nearly 5 million Americans
are currently living with heart failure, and more than half a million new
cases are diagnosed each year.
About AstraZeneca
AstraZeneca (NYSE: AZN) is a major international healthcare business
engaged in the research, development, manufacture and marketing of
prescription pharmaceuticals and the supply of healthcare services. It is one
of the world's leading pharmaceutical companies with healthcare sales of over
$21.4 billion and leading positions in sales of cardiovascular,
gastrointestinal, respiratory, oncology, and neuroscience products. In the
United States, AstraZeneca is a $9.6 billion healthcare business with more
than 12,000 employees. AstraZeneca is listed in the Dow Jones Sustainability
Index (Global) as well as the FTSE4Good Index.
For more information about AstraZeneca, please visit
http://www.astrazeneca-us.com.
This press release contains forward-looking statements with respect to
AstraZeneca's business. By their nature, forward-looking statements and
forecasts involve risks and uncertainties because they relate to events and
depend on circumstances that will occur in the future. There are a number of
factors that could cause actual results and developments to differ materially.
For a discussion of those risks and uncertainties, please see the company's
Annual Report/Form 20-F for 2004.
Candesartan Cilexetil is marketed by AstraZeneca under trademark ATACAND.
ATACAND is manufactured under agreement from Takeda Pharmaceutical Company
Limited.
SOURCE AstraZeneca
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Related links:
http://www.astrazeneca-us.com
http://www.atacand-us.com
Company News On-Call:
http://www.prnewswire.com/comp/985887.html
CONTACT:
Gary Bruell, AstraZeneca LP, +1-302-885-1554,
+1-610-322-0616 (Cell), gary.bruell@astrazeneca.com
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