Importantly, Atacand is the first Angiotensin Receptor Blocker (ARB) to increase survival in chronic heart failure patients with left ventricular dysfunction, whether or not they are taking an ACE-inhibitor.
CHARM co-chairman, Professor Karl Swedberg, Göteborg University and Sahlgrenska University Hospital/Östra, Göteborg, Sweden introduced the rationale behind the CHARM Programme: "While the incidence of most cardiovascular disease is stabilising, chronic heart failure remains a serious and costly condition with patients being symptomatic and at risk of early death. Although major advances in the treatment of heart failure have occurred in the last decade or so, there is still a real need for additional, effective therapies and this requirement led us to devise the CHARM Programme in order to evaluate the clinical benefits of candesartan in the treatment of this debilitating and distressing condition".
The CHARM Programme, which recruited 7,601 patients, is the largest ever trial programme conducted in heart failure with an AT1-receptor blocker. Patients with classic symptomatic chronic heart failure - depressed left ventricular (LV) systolic function (Left Ventricular Ejection Fraction (LVEF) < 40%), were randomised into one of two studies - either an ACE-inhibitor intolerant population (CHARM-Alternative), or the population treated with ACE-inhibitors (CHARM-Added). In addition, patients with preserved LV systolic function (LVEF> 40%) were also randomised into a third study (CHARM-Preserved). All patients received either Atacand (candesartan cilexetil) or placebo.
In patients who were not taking ACE-inhibitors due to previous intolerance, Atacand significantly reduced the risk of cardiovascular death or hospitalisation for chronic heart failure, with an overall risk reduction of 23% (p<0.0004). This is comparable to the benefit seen in heart failure studies using ACE-inhibitors alone.
Dr. Christopher Granger, lead investigator in the CHARM-Alternative study, Duke University Medical Center, Durham, North Carolina, USA, commented: "This trial shows that for the heart failure patients who cannot take ACE inhibitors, candesartan reduces death and hospital admission for heart failure by 23%, which is highly significant".
In patients that were prescribed conventional therapy for chronic heart failure including an ACE inhibitor, Atacand demonstrated additional mortality and morbidity benefits. Atacand produced an additional reduction in the risk of cardiovascular death or hospitalisation for chronic heart failure of 15% (p=0.011) when compared to conventional treatment alone. Importantly, Atacand demonstrated this efficacy, along with a high level of tolerability, when taken as part of triple combination therapy that included an ACE-inhibitor and beta-blocker - standard treatments in patients with chronic heart failure.
Commenting on the study, Professor John McMurray, principal investigator in the CHARM-Added study, Glasgow University and Western Infirmary, Glasgow, Scotland, said "That candesartan improved outcome, even when added to full conventional therapy, is a very important treatment advance for these very sick patients".
The CHARM Programme also included the largest completed trial in chronic heart failure 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 chronic heart failure showed a trend, 11% risk reduction in favour of Atacand (p=0.118), consistent with the significant findings seen in the other two studies - CHARM-Alternative and CHARM-Added. The total number of hospitalisations for CHF was significantly lower in the Atacand group (402 v 566). There was also a significant 40% reduction in the number of patients diagnosed with new onset diabetes (47 v. 77; p=0.005).
Principal investigator of the CHARM-Preserved study, Professor Salim Yusuf, McMaster University, Ontario, Canada stated: "This is the largest trial evaluating the role of any therapy in heart failure patients with preserved left ventricular function. The reduction in hospitalisations for heart failure in this trial provides evidence of clinical benefit".
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). Interestingly, it also demonstrated a significant 22% reduction in onset of new diabetes, with 163 new cases of diabetes on Atacand compared with 202 on placebo.
CHARM co-chairman, Professor Karl Swedberg summarised the data: "CHARM will influence the way that clinicians treat heart failure. We cannot ignore the fact that this treatment will save lives in heart failure regardless of whether the person is taking an ACE-inhibitor or beta blocker. The benefits are also irrespective of left ventricular ejection fraction."
Professor Marc Pfeffer, CHARM co-chairman, Professor of Medicine, Harvard Medical School and Senior Physician, Brigham and Women's Hospital, Boston, Massachusetts, USA commented: "We conducted a unique programme of research across a broad range of heart failure patients and found that candesartan reduced both cardiovascular death and hospital admissions for heart failure. The clinical effectiveness of candesartan offers the opportunity to further reduce these important outcomes in this expanding segment of our aging population".
For more information, please visit http://www.
Elizabeth Rickard - Ketchum
Anette Orheim - AstraZeneca
Onsite at ESC congress, Vienna
Onsite at ESC congress, Vienna
Ketchum, London office
Following data presentation, AstraZeneca media materials will be available on http://www.
A webcast of the CHARM hotline presentation will be posted on the official ESC website (http://www.
The results of the CHARM Programme will be published in The Lancet (http://www.
Notes to editors
*Candesartan in Heart failure - Assessment of Reduction in Mortality and morbidity (CHARM) study programme
- Recruiting 7,601 patients (long term follow up data from 7,599 patients)
- AstraZeneca is the sole sponsor of the CHARM programme. Patients were randomised to either Atacand® or placebo in a 1:1 ratio in each of the three component studies:
- ACE-inhibitor intolerant population (CHARM-Alternative): Comprising patients with depressed LV systolic function (LVEF< 40%) who could not tolerate ACE inhibitors.
- ACE-inhibitor treated population (CHARM-Added): Comprising patients with depressed LV systolic function (LVEF< 40%) who were also taking an ACE inhibitor.
- Preserved LV function population (CHARM-Preserved): Comprising patients with preserved LV systolic function (LVEF >40%), a history of hospitalization for a cardiac reason, with or without current treatment with an ACE inhibitor.
- 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 $17.8 billion and leading positions in sales of gastrointestinal, oncology, anaesthesia (including pain management), cardiovascular, central nervous system (CNS) and respiratory products. AstraZeneca is listed in the Dow Jones Sustainability Index (Global and European) as well as the FTSE4 Good 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 CRESTOR
TM, Atacand®, Zestril©, Seloken ZOK© /Toprol XL TMand Plendil©. This heritage is complemented by an innovative pipeline including the first oral direct thrombin inhibitor, Exanta TM, and a novel treatment for type 2 diabetes / metabolic syndrome GALIDA.
- Candesartan Cilexetil is marketed by AstraZeneca under trademark Atacand®. Atacand® is manufactured under agreement from Takeda Chemical Industries Ltd.
Information on AstraZeneca products - ExantaTM and CRESTORTM Exanta data being presented at this year's ESC congress:
- Exanta: Phase II ESTEEM study - Hotline, Monday 1st September, 9.45am - 9.55am (CET), in the Stockholm room, Green Zone, ESC Congress Centre: L.C. Wallentin. The first presentation of data on the efficacy and safety of long-term treatment with the oral direct thrombin inhibitor ximelagatran, in combination with acetylsalicyclic acid, in patients after acute myocardial infarction.
- Exanta: SPORTIF III - Clinical trial update, 12.12 - 12.25, Tuesday 2nd September, Rome Room, Blue Zone, ESC Congress Centre: S.B. Olsson. The first full presentation of data on stroke prevention using the oral direct thrombin inhibitor ximelagatran, compared with dose-adjusted warfarin, in patients with non-valvular atrial fibrillation.
One multi-national and two national studies are underway to examine the efficacy and safety of AstraZeneca's statin, CRESTORTM (rosuvastatin) in heart failure:
- CORONA (COntrolled Rosuvastatin multiNAtional trial in heart failure) is a long-term, randomised, double-blind, placebo controlled, multi-national study to evaluate rosuvastatin 10mg on cardiovascular mortality and morbidity and overall survival in 4950 patients aged 60 years or above with chronic symptomatic systolic heart failure (NYHA class II-IV) of ischaemic aetiology receiving standard treatment.
- GISSI-HF (Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca [Italian Group for the Study of the Survival in Cardiac Insufficiency]) an independent Italian study, investigating whether treatment with CRESTOR or fish oil improves mortality and morbidity of people with symptomatic heart failure of any aetiology already receiving standard treatment.
- UNIVERSE (RosUvastatiN Impact on VEntricular Remodelling lipidS and cytokinEs) in Australia which will assess the impact of CRESTOR compared to placebo on cardiac remodelling in heart failure patients.