New CHARM analysis adds further weight to effectiveness of Candesartan in treating heart failure

Main Category: Cardiovascular / Cardiology
Article Date: 31 Aug 2004 - 8:00 PDT

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

Data presented today at the European Society of Cardiology (ESC) Congress reinforces the benefits of Candesartan 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 Candesartan, adding further support to the previously presented results from the entire CHARM Programme1 on the effects of Candesartan 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 Candesartan was added to standard treatment.

With 29 deaths avoided per 1,000 treated patients investigators concluded that Candesartan 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 Candesartan was similar irrespective of background treatment with ACE-inhibitors, beta blockers or spironolactone.

"This data clearly shows the benefits of treatment with Candesartan 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 Candesartan 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 Candesartan 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 4576 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.

Candesartan is an angiotensin II type 1 (AT1) receptor blocker indicated for the treatment of high blood pressure. As a proven and leading antihypertensive therapy, Candesartan 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 Candesartan in treating hypertension and heart failure. In April, Takeda and AstraZeneca filed a regulatory application in the European Union (EU), as part of the Mutual Recognition Variation Procedure to obtain a new indication for Candesartan for use in the treatment of heart failure. An application was filed in the US by AstraZeneca on June 30 and further filings in other markets are expected in the near future.

CHARM study was sponsored and conducted by AstraZeneca. Candesartan was discovered and originally synthesized by TAKEDA PHARMACEUTICAL COMPANY LIMITED, and it was jointly developed with AstraZeneca. Candesartan is marketed worldwide under the brand name of Blopress® by Takeda and Atacand® by AstraZeneca in more than 70 countries.

-- ENDS --

For further information please contact:

"Medical Information"
Makoto Iwane
TAKEDA PHARMACEUTICAL COMPANY LIMITED
Strategic Development Dept.
Pharmaceutical Development Div.
(T) +81 (6) 6204 5302
(e) Iwane_Makoto@takeda.co.jp "Corporate Information" Shouji Wakayama TAKEDA PHARMACEUTICAL COMPANY LIMITED
Public Relation & Investor Relations
Corporate Communications Dept.
(T) +81 (6) 6204 2412
(e) Wakayama_Shouji@takeda.co.jp

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.

•-- Takeda is a global research-based pharmaceutical company, largest in Japan and one of the leaders in the world. Takeda is committed to striving toward better health for individuals and progress in medicine by developing superior pharmaceutical products.

-- From Takeda's own R&D activities, products such as Candesartan (marketed as Blopress®, Kenzen® and Amias®), pioglitazone, leuprolide and lansoprazole, have been successfully developed and are now available over 100 countries worldwide.

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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