Landmark heart failure study includes over 7500 participants - CHARM study programme recruitment completed on schedule

(Mölndal, Sweden, 2 March 2001) AstraZeneca today announced that the landmark heart failure study programme, CHARM (Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity)1 has completed recruitment on schedule. With more than 7500 participants, CHARM becomes the largest ever study of an AT1-receptor blocker in heart failure. The AT1-receptor blocker used in CHARM is candesartan cilexetil, Atacand,® a long-acting, once-daily drug with placebo-like tolerability. The aim of CHARM is to determine whether Atacand® can improve survival in a broad spectrum of patients with symptomatic heart failure.

The CHARM study programme is a huge undertaking being conducted at 618 sites in 26 countries and is unique in investigating a wide range of patients representing the entire spectrum of heart failure. Given the scale of the programme, the comprehensive nature of the patient population, and the inclusion of a large group of patients, more than 2000, who are intolerant of standard therapy with ACE inhibitors, CHARM will define the optimal role of AT1-receptor blockade with Atacand® in the management of heart failure. The CHARM study programme is expected to run until early 2003.

Professor Marc Pfeffer, Professor of Medicine, Harvard Medical School, and Co-Chairman of the CHARM Executive Committee, said: "The completion of patient recruitment for the CHARM study programme is a major achievement for everyone involved. CHARM is intended to contribute major insight into the development of better care for heart failure patients, leading to improved outcomes. The achievement of this milestone is a crucial step along the way but we still have a long way to go."

Professor Karl Swedberg, Professor of Medicine, Göteborg University, Sweden, and Co-Chairman of the CHARM Executive Committee, added: "Heart failure is a huge burden on the individual and society. The prevalence continues to rise as a result of the increasing ageing of the population and improved survival of people after myocardial infarction. Despite improvements in treatment, heart failure remains one of the most malignant of conditions, being as deadly as cancer.2 It is generally accepted that more effective management strategies are urgently needed. CHARM should help to meet those needs."

Confidence that the CHARM study programme will provide more definitive data on the benefits of AT1-receptor blockers in the treatment of heart failure than any other study involving this group of drugs is based on the study design and patient inclusion. The programme consists of three independent, parallel, placebo-controlled studies. One study is investigating a group of patients receiving Atacand® added to standard therapy including an ACE inhibitor. Another study is investigating a group of patients with congestive heart failure not previously studied i.e. with preserved left ventricular systolic function (LVEF > 40%). The third study specifically compares Atacand® and placebo in patients with impaired left ventricular function who are intolerant of ACE inhibitors. The size of this patient group i.e. over 2000 patients, should ensure that the value of Atacand® alone in the treatment of heart failure is definitively established.

Data exist to support the view that CHARM will position Atacand® as the therapy capable of improving mortality and morbidity in patients with heart failure.3 A recent study4 demonstrated increased exercise time following treatment with Atacand® in patients with mild-to-moderate heart failure. Atacand® demonstrates the placebo-like tolerability typical of AT1-receptor blockers, including patients with heart failure intolerant to ACE inhibitors,5 but 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 In clinical practice, these properties may translate into marked efficacy, a clear dose response and a long duration of action.

AstraZeneca 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 top five pharmaceutical companies in the world with healthcare sales of over $15.8 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:

Julia Cross, AstraZeneca Tel: +44 (0) 1625 510866
Anders Svensson, AstraZeneca R&D Mölndal Tel: +46 31 776 1000

Jean Kilshaw, Ketchum, Tel: +44 (0) 20 7465 7050

References

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 McMurray J. Why we need new strategies in CHF management. J RAAS 2000; 1: (Suppl 1) 12-16
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 angiotensin receptor antagonists on Chinese Hamster Ovary Cells expressing human angiotensin II type 1 receptors. Biochem Pharmacol 2000; 59: 927-935

Candesartan cilexetil, is an AT1-receptor blocker which was discovered by Takeda Chemical Industries, Ltd. and has been developed jointly by AstraZeneca and Takeda. The product is now available in most countries under the trade names Atacand® and/or Blopress® by AstraZeneca and Takeda respectively.