WILMINGTON, Del., Sept. 6 /PRNewswire-FirstCall/ -- Results were released
from a prospectively defined, secondary analysis of the Candesartan in Heart
Failure Assessment of Reduction in Mortality and morbidity (CHARM) program
evaluating the effects of the AstraZeneca angiotensin II receptor blocker
(ARB), ATACAND(R) (candesartan cilexetil), in reducing the risk of development
of diabetes in patients with heart failure and no previous diagnosis of
diabetes. In the overall CHARM program, 163 patients receiving ATACAND and
202 patients receiving placebo developed a new diagnosis of diabetes, for a
relative risk reduction on ATACAND of 22% (hazard ratio 0.78, 95% confidence
interval 0.64-0.96, p=0.020).(1) ATACAND is indicated for the treatment of
hypertension and heart failure (NYHA class II-IV, LVEF less than or equal to
40%), and is not indicated for the prevention of new onset diabetes. The
present analysis also included patients from the CHARM-Preserved trial (LVEF
>40%), which did not reach its primary endpoint.
"Diabetes is a serious and common risk factor for the development of
cardiovascular disease that may result in heart failure. The two conditions
are increasing in prevalence and are associated with high rates of mortality
and morbidity," said lead investigator, Salim Yusuf, DPhil, FRCP, Professor of
Medicine and Director, Division of Cardiology, McMaster University, Hamilton,
Canada. "This analysis evaluated the effects of candesartan in reducing the
risk of developing diabetes in addition to the established benefit of reducing
cardiovascular mortality and hospitalizations for heart failure."
This analysis adds to the body of literature on ARBs and diabetes.(2)
These data cannot be considered conclusive and this is an area of active
investigation.
About the CHARM program and this analysis(3)
The CHARM program, sponsored by AstraZeneca, consisted of 3 parallel,
randomized, placebo-controlled, double-blind trials in 7,599 symptomatic heart
failure patients. CHARM-Added (n=2548) and CHARM-Alternative (n=2028)
enrolled patients with left-ventricular ejection fraction (LVEF) less than or
equal to 40%, and CHARM-Preserved (n=3023) enrolled patients with LVEF > 40%.
Patients were randomized to either ATACAND or matching placebo initiated at 4
mg or 8 mg and titrated as tolerated to 32 mg once daily. Patients were
followed for a minimum of 2 years, with median follow-up of 37.7 months. The
primary end point of each trial was cardiovascular death or heart failure
hospitalization.
The CHARM program included 5,436 patients who did not have a diagnosis of
diabetes at randomization. The pre-specified analysis of new diagnosis of
diabetes found that 163 (6.0%) individuals in the group receiving ATACAND
developed diabetes, compared with 202 (7.4%) in the placebo group (relative
risk reduction 22%, hazard ratio 0.78, 95% confidence interval 0.64-0.96,
p=0.020). The composite end point of death or new diagnosis of diabetes
occurred in 25.2 percent of patients receiving ATACAND and 28.6 percent of
patients in the placebo group, giving a relative risk reduction of 14% (hazard
ratio 0.86, 95% confidence interval 0.78-0.95, p=0.004).(4)
In February 2005, the US Food and Drug Administration (FDA) approved
ATACAND for the treatment of heart failure (New York Heart Association Class
II-IV and ejection fraction less than or equal to 40 percent) to reduce the
risk of death from cardiovascular causes and reduce hospitalization for heart
failure. In May 2005, the FDA approved the current label: "ATACAND is
indicated for the treatment of heart failure (NYHA class II-IV) in patients
with left-ventricular systolic dysfunction (ejection fraction less than or
equal to 40%) to reduce cardiovascular death and to reduce heart failure
hospitalizations. ATACAND also has an added effect on these outcomes when
used with an ACE inhibitor." The approvals were based on positive results of
the CHARM-Alternative and CHARM-Added trials. In these patients with heart
failure, ATACAND is the only ARB proven to reduce both cardiovascular death
and heart failure hospitalizations and to provide these benefits with or
without an ACE inhibitor. ATACAND is the only ARB with these proven benefits
when used with conventional therapy that includes both an ACE inhibitor plus a
beta-blocker.
IMPORTANT SAFETY INFORMATION
USE IN PREGNANCY: 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. For full Prescribing
Information for ATACAND, including boxed WARNING, call 1-800-236-9933 or visit
http://www.atacand-us.com.
In heart failure patients receiving ATACAND, hypotension, increases in
serum creatinine, and hyperkalemia have occurred. Caution should be observed
for hypotension when initiating therapy. Evaluation of patients with heart
failure should always include assessment of renal function and volume status.
Monitoring of blood pressure, serum creatinine, and serum potassium is
recommended during dose escalation and periodically thereafter. During
concomitant use of ATACAND and lithium, careful monitoring of serum lithium
levels is recommended.
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), 21.0% of patients
discontinued ATACAND for adverse events vs. 16.1% of placebo patients.
About Heart Failure
Heart failure is a condition in which the heart is unable to pump blood
adequately to the rest of 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.(5) 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.(6) 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 a half million new
cases are diagnosed each year.(7)
About AstraZeneca
AstraZeneca (NYSE: AZN) is a major international health care business
engaged in the research, development, manufacture, and marketing of
prescription pharmaceuticals and the supply of health care services. It is
one of the world's leading pharmaceutical companies with health care 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 health care 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 the
AstraZeneca 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.
Manufactured under the license from Takeda Pharmaceutical Company, Ltd.
by: AstraZeneca AB, S-151, 85 Sodertalje, Sweden.
References
(1) Yusuf S, et al. Effects of Candesartan on the Development of a New
Diagnosis of Diabetes Mellitus in Patients with Heart Failure. Circulation.
2005;112:48-53.
(2) Ibid.
(3) Ibid.
(4) Ibid.
(5) Dosh SA. Diagnosis of heart failure in adults. Am Fam Physician.
2004;70(11):2145-52.
(6) Rich MW. Drug therapy of heart failure in the elderly. Am J Geriatr
Cardiol. 2003;12(4):235-242.
(7) American Heart Association. Heart Disease and Stroke Statistics-2005
Update. Dallas, Texas. American Heart Association; 2005.
SOURCE AstraZeneca
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Related links:
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http://www.atacand-us.com
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http://www.prnewswire.com/comp/985887.html
CONTACT:
Valerie Bomberger of AstraZeneca LP,
+1-302-885-4128 or valerie.bomberger@astrazeneca.com, or Jim
Minnick of AstraZeneca LP, +1-302-886-5135 or
jim.minnick@astrazeneca.com
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