News Release

New CHARM* analysis adds further weight to effectiveness of Atacand® in treating heart failure

Atacand® is proven to reduce deaths and hospitalisation in patients with heart failure and reduced left ventricular ejection fraction

Peer-Reviewed Publication

Ketchum UK

Embargoed until 08.30 CET, Munich, Germany, 31 August 2004: Data presented today at the European Society of Cardiology (ESC) Congress reinforces the benefits of Atacand® (candesartan cilexetil) in patients with chronic heart failure (CHF) and reduced left ventricular ejection fraction (LVEF). The data demonstrated a significant reduction in deaths and CHF hospital admissions in favour of Atacand®, adding further support to the previously presented results from the entire CHARM Programme1 on the effects of Atacand® in a broad spectrum of CHF patients.

A pre-specified analysis2 in the group of CHARM patients with heart failure and reduced LVEF (n=4576; LVEF = 40%), the higher risk population most frequently studied in previous heart failure clinical trials, demonstrated a 12% relative risk reduction in all cause deaths (p=0.018) and a 16% relative risk reduction in cardiovascular deaths (p=0.005) when Atacand® was added to standard treatment. With 29 deaths avoided per 1,000 treated patients investigators concluded that Atacand® should be considered in all patients with CHF and a low LVEF. This new analysis also shows a 24% relative risk reduction in CHF hospital admissions (p<0.001). The effect of treatment with Atacand® was similar irrespective of background treatment with ACE-inhibitors, beta blockers or spironolactone.

"This data clearly shows the benefits of treatment with Atacand® irrespective of other background life-saving therapies for these very sick patients" comments CHARM co-chairman, Professor Karl Swedberg, Göteborg University and Sahlgrenska University Hospital/Östra, Göteborg, Sweden. "Patients with heart failure and reduced left ventricular ejection fraction - the 'classic' heart failure population studied in major clinical trials - have a high risk of cardiovascular death and hospitalisation. The CHARM data shows that Atacand® can offer these patients a significant improvement by reducing mortality and improving symptoms, resulting in fewer hospital admissions".

The CHARM Programme consisted of three component trials comparing the angiotensin II type 1 (AT1) receptor blocker Atacand® to placebo. Two trials randomised patients with LVEF = 40%; the CHARM Alternative Trial3 (ACE – inhibitor intolerant patients) and the CHARM Added Trial4 (all patients on ACE-inhibitors) comprising a total of 4,576 patients with an average age of 65 years and a mean LVEF of 29%.

CHF is the only major cardiovascular disease with increasing incidence and prevalence and is a major public health problem. CHF continues to place a significant burden on patients and healthcare systems worldwide. As a major cause of death, hospital admissions and poor quality of life, CHF is believed to affect in the region of 1-2% of the general population5,6, rising to 8% in people over the age of 75 years7.

Atacand® is an angiotensin II type 1 (AT1) receptor blocker indicated for the treatment of high blood pressure. As a proven and leading antihypertensive therapy, Atacand® was first licensed in 1997 and has been shown to lower blood pressure more effectively than losartan, the first marketed member of the class8,9,10,11. Recent clinical outcome studies with SCOPE and CHARM, have demonstrated the clinical value of Atacand® in treating hypertension and heart failure. In April, AstraZeneca filed a regulatory application in the European Union (EU), as part of the Mutual Recognition Variation Procedure to obtain a new indication for Atacand® (candesartan cilexetil) for use in the treatment of heart failure. An application was filed in the US on June 30 and further filings in other markets are expected in the near future.

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For more information, please visit www.astrazenecapressoffice.com or contact:

Elizabeth Rickard - Ketchum
Onsite at the ESC Congress, Munich
Mobile: +44 7786 246 618
Email: elizabeth.rickard@ketchum.com

Anette Orheim
Onsite at the ESC Congress, Munich
Mobile: +46 709 13 19 52
Email: anette.orheim@astrazeneca.com

Stephanie Gardner
Ketchum, London office
Office: +44 20 7611 3510
Mobile: +44 7779 300 685
Email: stephanie.gardner@ketchum.com

Notes to editors

  • *Candesartan in Heart failure - Assessment of Reduction in Mortality and morbidity (CHARM) study programme
  • Ejection fraction is the percentage of blood in the left ventricle pumped into general circulation by the heart per beat. Many people with CHF have impaired left-ventricular (LV) systolic function where the ejection fraction is significantly compromised. In the CHARM Programme an ejection fraction of = 40% was taken to indicate impaired LV systolic function, although there is no agreed suboptimal ejection fraction to indicate impaired LV systolic function.

  • 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 $18.8 billion and leading positions in sales of gastrointestinal, oncology, cardiovascular, neuroscience and respiratory products. AstraZeneca is listed in the Dow Jones Sustainability Index (Global and European) as well as the FTSE4Good Index.

    AstraZeneca has more than 40 years experience in cardiovascular medicine and aims to increase lifespan and improve quality of life by reducing the risk, prevalence and impact of cardiovascular disease. AstraZeneca has a comprehensive cardiovascular portfolio including portfolio including CRESTOR, Atacand, Zestril, Tenormin, SELOKEN ZOK/TOPROL-XL and Plendil*. This heritage is complemented by an innovative pipeline including the first oral direct thrombin inhibitor, Exanta*, and a novel treatment for type 2 diabetes / metabolic syndrome, GALIDA *.

    *CRESTOR, Atacand, Zestril, Tenormin, SELOKEN ZOK/TOPROL-XL, Plendil, Exanta and GALIDA are trademarks of the AstraZeneca group of companies.

  • Candesartan Cilexetil is marketed by AstraZeneca under trademark Atacand®. Atacand® is manufactured under agreement from Takeda Pharmaceutical Company Limited.

  • Atacand® is marketed in the UK as Amias® and Italy as Ratacand®

  • AstraZeneca is the developer and sole sponsor of the CHARM Programme. The CHARM Programme, which recruited 7,601 patients, is the largest ever trial programme conducted in heart failure with an AT1-receptor blocker. Patients were randomised to either Atacand® or placebo in a 1:1 ratio in each of the three component studies. The CHARM results showed that Atacand® is the first AT1-receptor blocker to increase survival in chronic heart failure patients with left ventricular dysfunction, whether or not they are taking an ACE-inhibitor. In patients who were not taking ACE-inhibitors due to previous intolerance, Atacand® significantly reduced the risk of cardiovascular death or hospitalisation for CHF, the relative risk reduction being 23% (p<0.0004). Also in patients who were prescribed conventional therapy for chronic heart failure including an ACE inhibitor, Atacand® demonstrated mortality and morbidity benefits. Atacand® produced a relative risk reduction of cardiovascular death or hospitalisation for chronic heart failure of 15% (p=0.011) when compared to conventional treatment alone. The CHARM Programme also included the largest completed trial in CHF patients with preserved LV function, patients for whom little evidence based treatment guidance presently exist. In CHARM-Preserved the primary endpoint of cardiovascular death or hospitalisations for CHF showed a trend, 11% relative risk reduction in favour of Atacand® (p=0.118), consistent with the significant findings seen in the other two studies. Pooled analysis of the three studies showed that Atacand® provided a significant reduction in cardiovascular death and also demonstrated a positive trend in the overall reduction in all cause mortality approaching statistical significance (p=0.055).

    Additional AstraZeneca cardiovascular media activity at the ESC Congress 2004:

  • CHARM Programme – Further data – Poster presentation, Tuesday 31 August, 08.30 – 12.30, Poster Hall, Messe München GmbH. James Young. Presentation of a pre-specified analysis on the effects of Atacand® in patients with heart failure and reduced left ventricular ejection fraction, the higher risk population most frequently studied in previous heart failure clinical trials

  • 'Breaking the Hypertension to Heart Failure Chain' – Media Workshop, Tuesday 31 August, 13.30 – 15.00, Industry Press Conference Room, ESC Press Centre. Eminent speakers will lead what promises to be an informative and stimulating workshop on the link between hypertension and heart failure, with a focus on the clinical developments aimed at breaking the chain. A specialist research nurse will provide a unique insight into the realities of living with heart failure

  • SPORTIF III and V: final results of pooled analysis. Presented by Professor Bertil Olsson at: Atrial Fibrillation - Good Vibrations? - Official ESC presentation - Sunday 29 August, 12.40 - 13.20, Industry Press Conference Room, ESC Press Centre

  • Stroke Prevention with the Oral Direct Thrombin Inhibitor Ximelagatran - Scientific Presentation - Wednesday 1 September, 11.00 - 12.30, Prague, Red Zone. Final results of the pooled analysis of the SPORTIF III and V trials for stroke prevention with the oral direct thrombin inhibitor ximelagatran in patients with nonvalvular atrial fibrillation

    References

    1.Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJV, Michelson EL et al. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet 2003;362:759-66.

    2. Young J, Swedberg K, Dunlap ME, et al. Substantial reduction in all-cause mortality and morbidity with candesartan in patients with chronic heart failure and systolic left ventricular dysfunction: results of the CHARM low EF trials. Presented at the European Society of Cardiology (ESC) Congress, Tuesday, 31 August 2004, 08.30 – 12.30

    3. Granger CB, McMurray JJV, Yusuf S, Held P, Michelson EL, Olofsson B, et al. Effects of candesartan in patients with chronic heart failure and reduced left ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. Lancet 2003;362:772-76.

    4. McMurray JJV, Östergren J, Swedberg K, Granger CB, Held P, Michelson EL, et al. Effects of candesartan in patients with chronic heart failure and reduced left ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Added trial. Lancet 2003;362:767-71.

    5. Swedberg K et al. Candesartan in Heart Failure – Assessment of Reduction in Mortality and Morbidity (CHARM): Rationale and Design. J Card Fail 1999;5:276-282

    6. Swedberg K et al. Candesartan in Heart Failure – Assessment of Reduction in Mortality and Morbidity (CHARM) Study Programme. Blood Pressure 2000;9 (suppl 1):60

    7. Erdmann E. Foreword. Eur Heart J 1998;19(suppl P):P1

    8. Andersson OK, Neldam S. The antihypertensive effect and tolerability of candesartan cilexetil, a new generation angiotensin II antagonist, in comparison with losartan. Blood Press 1998; 7:53-9.

    9. Lacourciere Y, Asmar R. A comparison of the efficacy and duration of action of candesartan cilexetil and losartan as assessed by clinic and ambulatory blood pressure after a missed dose, in truly hypertensive patients: a placebo-controlled, forced titration study. Candesartan/Losartan study investigators. Am J Hypertens 1999; 12:1181-7.

    10. Bakris G, Gradman A, Reif M, Wofford M, Munger M, Harris S, et al. Antihypertensive efficacy of candesartan in comparison to losartan: the CLAIM study. J Clin Hypertens 2001;3:16–21.

    11. Vidt DG, White WB, Ridley E, Rahman M, Harris S, Vendetti J, et al. CLAIM Study Investigators. A forced titration study of antihypertensive efficacy of candesartan cilexetil in comparison to losartan: CLAIM Study II. J Hum Hypertens 2001;15:475–80.

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