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.
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
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.
Additional AstraZeneca cardiovascular media activity at the ESC Congress 2004:
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.
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7. Erdmann E. Foreword. Eur Heart J 1998;19(suppl P):P1
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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.