Landmark Study Shows ATACAND(R) Reduces Risk of Cardiovascular Death in Patients With Chronic Heart Failure and Diminished LV Function
Sunday August 31, 5:00 am ET
ATACAND is the first angiotensin receptor blocker (ARB) shown to reduce chronic heart failure (CHF) hospital admissions in patients with heart failure, when given together with conventional therapy
WILMINGTON, Del., Aug. 31 /PRNewswire-FirstCall/ -- In the most comprehensive trial program to date with an angiotensin receptor blocker (ARB) for heart failure, AstraZeneca's ATACAND® (candesartan cilexetil), has been shown to improve survival in patients with chronic symptomatic heart failure (CHF), and diminished left ventricle (LV) function (LVEF < or = 40%). The overall program results demonstrate that ATACAND (n=1150) reduces cardiovascular (CV) deaths or hospital admissions for heart failure by 16% when compared to placebo (n=1310) (p=<0.0001), across a broad spectrum of patients with symptomatic heart failure, irrespective of other concomitant heart failure therapies, ejection fraction, age or gender. ATACAND is approved for the treatment of hypertension, it is not currently indicated for heart failure.
Findings from the clinical program known as CHARM (Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity) were presented today at the annual meeting of the European Society of Cardiology Congress.
"CHARM is one of the most ambitious clinical trial programs in heart failure ever undertaken in terms of its scale and scope," said Marc Pfeffer, M.D., CHARM Co-Chairman, Professor of Medicine, Harvard Medical School, and Senior Physician, Brigham & Women's Hospital Boston, MA.
CHARM is an international, multi-center program involving 7,601 patients with classic symptoms of chronic heart failure and is comprised of three independent, parallel, double blind, placebo-controlled studies of ATACAND: patients with left ventricular systolic dysfunction (LVEF < or = 40%) in addition to standard therapy including an ACE inhibitor (CHARM Added); patients with LVEF < or = 40% who are intolerant of ACE inhibitors (CHARM Alternative); and patients with preserved left ventricular systolic function (LVEF > 40%) (CHARM Preserved). 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. All patients were followed for a minimum of two years.
In the CHARM program ATACAND was generally well tolerated but associated with a greater occurrence of discontinuation of study medication compared to placebo due to an increase in serum creatinine (6.2% vs. 3.0%) hypotension (3.5% vs. 1.7%), and hyperkalemia (2.2% vs. 0.6%). Please consult complete prescribing information, including the boxed warning regarding use during pregnancy.
The CHARM Program Findings
The CHARM Added trial demonstrated that in patients taking ACE inhibitors or beta-blockers as part of standard therapy, ATACAND provided a 15% reduction in the risk of CV death or CHF hospital admissions (n=483) when compared to placebo (n=538) (p=0.011).
"Chronic heart failure is a very serious medical condition where the heart has been injured or damaged," said Dr. James Young, Vice Chairman of the Department of Cardiovascular Medicine and Medical Director of the Kaufman Center for Heart Failure, Cleveland Clinic Foundation.
In the CHARM Alternative trial (patients who were unable to tolerate ACE inhibitors), ATACAND (n=334) significantly reduced the risk of CV death or hospital admissions for CHF by 23% (p=0.0004) as compared to placebo (n=406).
"This is the first time this group of patients has been studied in large numbers over a long period," said Dr. Christopher Granger, lead investigator in the CHARM Alternative study, from Duke University Medical Center in Durham, North Carolina. "Which is important since there is a substantial portion of patients with chronic heart failure who cannot tolerate an ACE inhibitor."
The CHARM Preserved trial is the first large-scale trial to evaluate the effect of drug therapy on CV death and hospitalization for CHF in this patient population with preserved left ventricular function (LVEF > 40%). While deaths from CV events were unaffected, hospital admissions for CHF were reduced in patients receiving ATACAND (n=402) compared to those receiving placebo (n=566) (p=0.014).
Principal investigator of the CHARM-Preserved study, Professor Salim Yusuf, McMaster University, Ontario, Canada stated: "This is the largest trial evaluating the role of any therapy in heart failure patients with preserved left ventricular function."
In the planned overall analysis of the three trials in the CHARM program ATACAND (n=886) compared to placebo (n=945) demonstrated a 9% reduction in the risk of death from any cause in a broad spectrum of patients with heart failure (p=0.055). There were 12% fewer CV deaths in the ATACAND group (n=691), compared with the placebo group (n=769)(p=0.012); and 21% reduction in hospital admissions for CHF in the ATACAND group (n=757) versus placebo (n=918) (p<0.0001).
About ARBs and ATACAND
Angiotensin II receptor blockers work by inhibiting the effects of angiotensin II, a peptide that constricts blood vessels and contributes to hypertension. ATACAND is indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents. The usual recommended starting dose of ATACAND is 16 mg once daily as monotherapy in patients who are not volume depleted. ATACAND can be administered once or twice daily with total daily doses ranging from 8 mg to 32 mg. The three most common adverse events occurring with ATACAND more often than placebo were upper respiratory tract infection (URI) (6% vs. 4%), dizziness (4% vs. 3%), and back pain (3% vs. 2%).
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. For full Prescribing Information for ATACAND, including boxed WARNING, call 1-800-236-9933 or visit www.atacand-us.com . |
