AstraZeneca reaffirms belief in CHARM study

November 14, 2000

New data reinforce the relevance of the CHARM study programme in investigating the benefits of AT1-receptor blockade in heart failure

(Mölndal, Sweden, 15 November 2000) AstraZeneca today welcomed the results of the Val-HeFT study which showed significant effects of an AT1-receptor blocker on mortality and morbidity in patients with heart failure when added to ACE inhibitor therapy.

Professor Peter Held, the AstraZeneca physician responsible for the CHARM study programme, currently investigating the efficacy of candesartan cilexetil (Atacand®) in heart failure, commented: "The Val-HeFT results are the first positive outcome data in heart failure with the AT1- receptor blocker class of antihypertensive agents.

They highlight the potential of the class in this serious and disabling condition and provide strong encouragement for the thousands of patients enrolled in the CHARM study programme and the physicians responsible for their care."

The CHARM study programme is investigating a much broader range of patient types and treatment scenarios than Val-HeFT and leading AT1 -receptor blocker investigators are confident that it will provide even more definitive and conclusive data.

Professor Marc Pfeffer, Professor of Medicine, Harvard Medical School and Co-Chairman of the CHARM Executive Committee, said: "The Val-HeFT investigators are to be congratulated on conducting an important study.

They have shown that the addition of an AT1-receptor blocker to conventional therapy in patients with heart failure leads to an improvement in clinical outcome. These findings are promising and underscore the importance of other ongoing investigations with AT1-receptor blockers in heart failure."

Professor Pfeffer continued: "The CHARM study programme goes further than Val-HeFT in that it is designed to determine outcomes in the entire heart failure spectrum, including patients with depressed or preserved ventricular function and those tolerant of as well as intolerant of ACE inhibitors.

For these reasons we believe that CHARM will provide physicians with new and vital information and a greater insight into the optimal use of AT1-receptor blockade, and in particular candesartan cilexetil, in patients with heart failure."

Professor Karl Swedberg, Professor of Medicine, Göteborg University, Sweden, and Co-Chairman of the CHARM Executive Committee, further stated: "With regard to testing the 'add-on' hypothesis for the use of AT1-receptor blockers in heart failure i.e. determining their impact on top of standard therapy with an ACE inhibitor, we believe that the important differences in the baseline characteristics between the Val-HeFT and CHARM patients underscore the need for the independent validation of the hypothesis that the CHARM study programme will provide."

Confidence that the CHARM study programme will provide more definitive data on the benefits of AT1-receptor blockers in the treatment of heart failure is based on study design and patient inclusion.

The patient population enrolled in the combination arm of CHARM displays different baseline characteristics than those enrolled in the Val-HeFT study.1,2 One arm of the study is investigating a group of patients with congestive heart failure not previously studied i.e. with preserved left ventricular systolic function (LVEF > 40%).

Another arm specifically includes patients with impaired left ventricular function who are intolerant of ACE inhibitors. This allows a comparison of Atacand® (candesartan cilexetil) and placebo without concomitant treatment with ACE inhibitors.

Significant data exist to support the hypothesis that CHARM will position Atacand® as the therapy capable of improving mortality and morbidity in patients with heart failure. The RESOLVD pilot study3 demonstrated that Atacand® in combination with enalapril was more beneficial in preventing left ventricular remodelling than either enalapril or Atacand® alone.

Strong mechanistic evidence also exists to support the use of Atacand® in heart failure. A recent study4 demonstrated increased exercise time following treatment with Atacand® in patients suffering mild-to-moderate symptomatic heart failure. The placebo-like tolerability in patients with heart failure who had proven to be intolerant to ACE inhibitors is also noteworthy.5

The CHARM study programme will also help to determine if differences in characteristics of individual AT1-receptor blocking drugs have clinical significance in heart failure. Atacand® is distinguishable from other drugs in the class by its tighter receptor binding properties6 as well as exhibiting the slowest dissociation from the AT1-receptor compared to any other member of the class studied.7,8,9

The CHARM study programme started recruitment during spring 1999 and is expected to run until 2002. The study is being carried out in 26 countries and over 7,300 patients have been included in the programme which will soon finish its recruitment phase.

AstraZeneca is a major international healthcare business engaged in the research, development, manufacture and marketing of ethical (prescription) pharmaceuticals and the supply of healthcare services.

It is one of the top five pharmaceutical companies in the world with healthcare sales of over $15 billion and leading positions in sales of gastrointestinal, oncology, anaesthesia including pain management, cardiovascular, central nervous system (CNS) and respiratory products.
For further information please contact: Alison MacKenzie at Tel: 44-207-465-8737, Fax: 44-207-872-9679 or E-mail: or Professor Peter Held Clinical Research and Development AstraZeneca R&D Mölndal, S-431 83 Mölndal, Sweden, Tel: 46-31-776-1900, Fax: 46-31-776-3712.


1. Swedberg K, Pfeffer M, Granger C et al. Candesartan in heart failure - assessment of reduction in mortality and morbidity (CHARM): Rationale and design. J Cardiac Failure 1999; 5: 276-282

2. Cohn JN, Tognoni G, Glazer RD et al. Rationale and design of the valsartan heart failure trial: a large multinational trial to assess the effects of valsartan, an angiotensin-receptor blocker, on morbidity and mortality in chronic congestive heart failure. J Cardiac Failure 1999; 5: 155-160

3. McKelvie RS, Yusuf S, Pericak D, et al. Comparison of candesartan, enalapril, and their combination in congestive heart failure: Randomised Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) Pilot Study: The RESOLVD Pilot Study Investigators. Circulation 1999;100:1056-64.

4. Riegger GAJ, Bouzo H, Petr P et al. Improvement in exercise tolerance and symptoms of congestive heart failure during treatment with candesartan cilexetil. Circulation 1999;100:2224 -30.

5. Granger C, Ertl G, Kuch J, et al. Randomized trial of candesartan cilexetil in the treatment of patients with congestive heart failure and a history of intolerance to angiotensin-converting enzyme inhibitors. Am Heart J 2000;139:609-17.

6. Timmermans PBMWM. Pharmacological properties of angiotensin II receptor antagonists. Can J Cardiol 1999;15 (Suppl F):26F-8F.

7. Morsing P, Adler G, Brandt-Eliasson U, Karp L, Ohlson K, Renberg L, Sjöquist P-O, Abrahamsson T. Mechanistic differences of various AT1-receptor blockers in isolated vessels of different origin. Hypertension 1999;33:1406-13.

8. Vanderheyden PML, Fierens FLP, De Backer JP, Fraeyman N, Vauquelin G. Distinction between surmountable and insurmountable selective AT1 receptor antagonists by use of CHO-K1 cells expressing human angiotensin II AT1 receptors. Br J Pharmacol 1999;126:1057-65 (a)

9. Vanderheyden PML, Fierens FLP, De Backer J-P, Vauquelin G. Reversible and syntopic interaction between AT1 receptor antagonists on CHO-K1 cells expressing human angiotensin II AT1 receptors. Biochem Pharmacol 2000 (in press). (b)

Ketchum UK

Related Heart Failure Articles from Brightsurf:

Top Science Tip Sheet on heart failure, heart muscle cells, heart attack and atrial fibrillation results
Newly discovered pathway may have potential for treating heart failure - New research model helps predict heart muscle cells' impact on heart function after injury - New mass spectrometry approach generates libraries of glycans in human heart tissue - Understanding heart damage after heart attack and treatment may provide clues for prevention - Understanding atrial fibrillation's effects on heart cells may help find treatments - New research may lead to therapy for heart failure caused by ICI cancer medication

Machining the heart: New predictor for helping to beat chronic heart failure
Researchers from Kanazawa University have used machine learning to predict which classes of chronic heart failure patients are most likely to experience heart failure death, and which are most likely to develop an arrhythmic death or sudden cardiac death.

Heart attacks, heart failure, stroke: COVID-19's dangerous cardiovascular complications
A new guide from emergency medicine doctors details the potentially deadly cardiovascular complications COVID-19 can cause.

Autoimmunity-associated heart dilation tied to heart-failure risk in type 1 diabetes
In people with type 1 diabetes without known cardiovascular disease, the presence of autoantibodies against heart muscle proteins was associated with cardiac magnetic resonance (CMR) imaging evidence of increased volume of the left ventricle (the heart's main pumping chamber), increased muscle mass, and reduced pumping function (ejection fraction), features that are associated with higher risk of failure in the general population

Transcendental Meditation prevents abnormal enlargement of the heart, reduces chronic heart failure
A randomized controlled study recently published in the Hypertension issue of Ethnicity & Disease found the Transcendental Meditation (TM) technique helps prevent abnormal enlargement of the heart compared to health education (HE) controls.

Beta blocker use identified as hospitalization risk factor in 'stiff heart' heart failure
A new study links the use of beta-blockers to heart failure hospitalizations among those with the common 'stiff heart' heart failure subtype.

Type 2 diabetes may affect heart structure and increase complications and death among heart failure patients of Asian ethnicity
The combination of heart failure and Type 2 diabetes can lead to structural changes in the heart, poorer quality of life and increased risk of death, according to a multi-country study in Asia.

Preventive drug therapy may increase right-sided heart failure risk in patients who receive heart devices
Patients treated preemptively with drugs to reduce the risk of right-sided heart failure after heart device implantation may experience the opposite effect and develop heart failure and post-operative bleeding more often than patients not receiving the drugs.

How the enzyme lipoxygenase drives heart failure after heart attacks
Heart failure after a heart attack is a global epidemic leading to heart failure pathology.

Novel heart pump shows superior outcomes in advanced heart failure
Severely ill patients with advanced heart failure who received a novel heart pump -- the HeartMate 3 left ventricular assist device (LVAD) -- suffered significantly fewer strokes, pump-related blood clots and bleeding episodes after two years, compared with similar patients who received an older, more established pump, according to research presented at the American College of Cardiology's 68th Annual Scientific Session.

Read More: Heart Failure News and Heart Failure Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to