23rd Feb 2005 13:30
AstraZeneca PLC23 February 2005 FDA APPROVES ASTRAZENECA'S ATACAND(R) (CANDESARTAN CILEXETIL) FOR THE TREATMENT OF HEART FAILURE AstraZeneca today announced that the US Food and Drug Administration (FDA) hasapproved its angiotensin receptor blocker (ARB) ATACAND(R) (candesartancilexetil) for the treatment of heart failure (New York Heart Association ClassII-IV and ejection fraction less than or equal to 40 percent) to reduce the riskof death from cardiovascular causes and reduce hospitalisations from heartfailure. ATACAND is the first ARB in the US to receive an indication forreducing both cardiovascular mortality and hospitalisations for heart failure. The US approval was primarily based on results from Candesartan in Heart FailureAssessment of Reduction in Mortality and morbidity Alternative Trial(CHARM-Alternative), which examined the effect of ATACAND (n= 1013) compared toplacebo (n=1015) in 2028 heart failure patients who were intolerant to ACEinhibitors, but were receiving other standard heart failure therapy. In mostcases, the starting dose of ATACAND was 4 mg once daily, which was doubled everytwo weeks up to the sixth week. Patients received the highest dose tolerated upto the target dose of 32 mg once daily. Patients were evaluated at 2, 4, and6 weeks; at 6 months; and every 4 months after until the end of the trial (34months on average). The primary endpoint was time to either cardiovascularmortality or hospitalisation for heart failure. The trial demonstrated that, inthese CHF patients, the use of ATACAND resulted in a 23 percent (p less than0.001) relative risk reduction in cardiovascular death or heart failurehospitalisation (406 events in the placebo arm compared to 334 events in thepatients receiving ATACAND), with both components contributing to this effect. This finding was supported by a second study of 2548 subjects (CHARM-Added) withNew York Heart Association (NYHA) Class II-IV heart failure and ejectionfraction less than or equal to 40 percent, in which subjects were already on ACEinhibitors. Together, in these studies, patients on ATACAND had a 15 percentlower risk of cardiovascular mortality (p=0.005). In these studies, symptomsof heart failure as assessed by NYHA functional class were also improved (p lessthan 0.001). Heart failure, also called chronic heart failure or CHF, is a condition in whichthe heart is unable to pump blood adequately to the rest of the body. It is aserious, progressive, debilitating condition and frequently leads to a fataloutcome. Many heart failure patients have impaired left ventricular systolicfunction and this is the population that has been studied in most previous heartfailure trials. In these patients, the heart's ability to function as a pump iscompromised, as evidenced by a reduced ejection fraction, which is thepercentage of blood ejected by the heart with each contraction. The normalheart ejects more than 50 percent of the blood in the left ventricle with eachbeat. Common causes of heart failure include coronary artery disease, heartattacks (or myocardial infarction), high blood pressure (or hypertension), andheart disease of unknown origin (or cardiomyopathy). New York Heart Association (NYHA) Classification is a widely used and validatedmeasure of symptomatic limitation in CHF. Class I: No limitation. Ordinaryphysical exercise does not cause fatigue, dyspnoea (breathlessness) orpalpitations. Class II: Slight limitation of physical activity. Comfortable atrest but ordinary physical activity results in symptoms. Class III: Markedlimitation of physical activity. Comfortable at rest but less than ordinaryactivity results in symptoms. Class IV: Unable to carry out any physicalactivity without discomfort. Symptoms present even at rest with increaseddiscomfort with any physical activity. The American Heart Association estimates that nearly 5 million Americans arecurrently living with heart failure, and more than half a million new cases arediagnosed each year. The recommended initial dose of ATACAND for the treatment of heart failure is 4mg once daily. The target dose is 32 mg once daily, which is achieved bydoubling the dose at approximately two-week intervals, as tolerated by thepatient. In November 2004, AstraZeneca announced that the European Mutual RecognitionVariation Procedure (MRP) evaluating the use of ATACAND for the treatment ofpatients with heart failure and impaired left ventricle systolic function hadbeen completed. Worldwide sales of ATACAND totalled $879 million for 2004. Candesartan Cilexetil is marketed by AstraZeneca under trademark ATACAND(R).ATACAND(R) is manufactured under agreement from Takeda Pharmaceutical CompanyLimited. 23rd February 2005 Media Enquiries:Edel McCaffrey, Tel: +44 (0) 207 304 5034Steve Brown, Tel: +44 (0) 207 304 5033 Investor Relations:Mina Blair, Tel: +44 (0) 207 304 5084Jonathan Hunt, Tel: +44 (0) 207 304 5087 -Ends- This information is provided by RNS The company news service from the London Stock ExchangeRelated Shares:
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