Incidence Of Atrial Fibrillation Significantly Reduced By Atacand(R) Therapy In Heart Failure Patients

Main Category: Cardiovascular / Cardiology
Article Date: 10 Jul 2006 - 0:00 PST

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New data published in the American Heart Journal show that Atacand(R) (candesartan cilexetil) is the first angiotensin receptor blocker (ARB) to significantly reduce the incidence of atrial fibrillation (AF) in a wide spectrum of heart failure patients, including those with preserved as well as reduced left ventricular systolic function, when added to contemporary therapy. Incidence of AF in the heart failure population is high at 10%-30%(2).

Atrial fibrillation is associated with a decline in cardiac function and worsening of heart failure symptoms including reduction in exercise capacity as well as deterioration in functional class(2). This in turn, may lead to hospital admission, increased morbidity for example stroke, and ultimately to death. Treatments with the potential to prevent AF in heart failure could therefore confer important clinical benefits. CHARM investigators prespecified the incidence of new AF as a secondary outcome of the trial comparing candesartan to placebo - 6,379 of the 7,601 patients in the overall CHARM population did not have AF at baseline and these patients were included in the new secondary analysis.

Lead investigator Dr Anique Ducharme, Montreal Heart Institute, Montreal, Canada, commented: "These exciting data are the first to show that the ARB Atacand can reduce the incidence of AF in such a wide spectrum of heart failure patients including those receiving standard optimal therapy. The development of AF is clearly undesirable in chronic heart failure and treatments that can prevent it offer a significant advance in the management of CHF."

The new analysis of the CHARM Programme at a median follow up time of 37.7 months shows that 5.55% of patients in the candesartan group were reported to have experienced one or more episodes of AF compared to 6.74% in the placebo group (p=0.048). The relative risk reduction for the incidence of AF was 17.7% for Atacand treatment compared to placebo. Consistent reduction rates of AF were observed in patient groups across varying severities of heart failure symptoms, and with concomitant drugs such as anti-arrhythmic agents, ACE inhibitors, beta-blockers and spironolactone.

These results are consistent with those from previous trials which have indicated that ARBs may reduce atrial fibrillation(3,4) though this study is the first to demonstrate a reduction in the incidence of AF with an ARB in such a wide spectrum of patients with symptomatic heart failure(1).

Atacand is now approved for the treatment of heart failure in more than 60 countries including the US and the EU.

The approval of a CHF indication for Atacand is based on the positive results of the CHARM Study Programme. The results from CHARM identified Atacand as the first ARB to reduce both death and heart failure hospital admissions in chronic heart failure patients with left ventricular systolic dysfunction, irrespective of background therapy(5).

Link to Atacand web site.

-- 6,379 of the 7,601 patients in the overall CHARM population did not have AF at baseline and these patients (3,191 on Atacand) were included in the new secondary analysis
-- The MRP on this occasion covered all EU countries apart from France. The reference member state during this procedure was the UK. (* EU countries excluding France and prior to 2004 expansion. Belgium, Denmark, Germany, Greece, Spain, Ireland, Italy, Luxembourg, Netherlands, Austria, Portugal, Finland, Sweden, United Kingdom)
-- 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 world's leading pharmaceutical companies with healthcare sales of $23.95 billion and leading positions in sales of gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infection products. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4Good Index.
-- Candesartan cilexetil is marketed by AstraZeneca under trademark Atacand(R), Ratacand(R), and is manufactured under the license from Takeda Pharmaceutical Company Ltd

References

1 - Ducharme A, Swedberg K, Pfeffer MA, et al. Prevention of atrial fibrillation in patients with symptomatic chronic heart failure by candesartan in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program. American Heart Journal 2006;

2 - Offutt C. Atrial fibrillation in the heart failure population. Cardiovascular Nurse 2004;19(Suppl 6):S3-10

3 - Maggioni A, Latini R, Carson P, et al. Valsartan reduces the incidence of atrial fibrillation in patients with heart failure: Results from the Valsartan Heart Failure Trial (Val-HeFT). American Heart Journal 2005;149:548-57

4 - Wachtell K, Lehto M, Gerdts E, et al. Angiotensin II receptor blockade reduces new-onset atrial fibrillation and subsequent stroke compared to atenolol: the Losartan Intervention For End Point Reduction in Hypertension (LIFE) study. Journal of the American College of Cardiology 2005;45:712-9

5 - Young JB, Dunlap ME, Pfeffer MA, et al. Mortality and morbidity reduction with candesartan in patients with chronic heart failure and left ventricular systolic function. Results from the CHARM low-left ventricular ejection fraction trials. Circulation 2004;110:2618-26