Candesartan in Heart Failure Presented at European Society of Cardiology 2003 CHARM Trial

www. Clinical trial results.org CHARM Added  Patients with LVEF <40% and treated with an ACE-inhibitor CHARM Added  Patients with LVEF <40% and treated with an ACE-inhibitor CHARM Alternative  Patients with LVEF <40% and ACE-inhibitor intolerant CHARM Alternative  Patients with LVEF <40% and ACE-inhibitor intolerant Endpoints (follow-up minimum 2 years):  Primary – Component trials: cardiovascular mortality or CHF hospitalization  Primary – Overall trial results: All-cause mortality Endpoints (follow-up minimum 2 years):  Primary – Component trials: cardiovascular mortality or CHF hospitalization  Primary – Overall trial results: All-cause mortality CHARM Trial European Society of Cardiology ,601 patients with heart failure 3 Individual component randomized trials with the ARB candesartan (4 or 8 mg/day, titrated to target dose of 32 mg) or placebo 7,601 patients with heart failure 3 Individual component randomized trials with the ARB candesartan (4 or 8 mg/day, titrated to target dose of 32 mg) or placebo CHARM Preserved  Patients with LVEF >40% with or without ACE-inhibitor CHARM Preserved  Patients with LVEF >40% with or without ACE-inhibitor

www. Clinical trial results.org CHARM Overall Program All-cause mortality HR % CI p=0.055 European Society of Cardiology 2003 CV Mortality or CHF Hospitalization HR 0.84 p<0.0001

www. Clinical trial results.org CHARM Added Trial CV Mortality or CHF hospitalization HR 0.85 p=0.011 European Society of Cardiology 2003 CV Mortality HR 0.84 p=0.02

www. Clinical trial results.org CHARM Alternative Trial CV Mortality or CHF hospitalization HR 0.77 p= European Society of Cardiology 2003 CV Mortality HR 0.85 p=0.072

www. Clinical trial results.org CHARM Preserved Trial CV Mortality or CHF hospitalization HR 0.89 p=0.118 European Society of Cardiology 2003 CV Mortality HR 0.99 p=0.918

www. Clinical trial results.org CHARM Trial CHARM Overall: Among symptomatic heart failure patients, treatment with ARB candesartan was associated with lower CV mortality and a trend toward lower all-cause mortality compared with placebo CHARM Added: Among patients with symptomatic heart failure and an ejection fraction <40% treated with an ACE-inhibitor, additional treatment with the ARB candesartan was associated with reduction in the primary endpoint of cardiovascular death or heart failure hospitalizations CHARM Overall: Among symptomatic heart failure patients, treatment with ARB candesartan was associated with lower CV mortality and a trend toward lower all-cause mortality compared with placebo CHARM Added: Among patients with symptomatic heart failure and an ejection fraction <40% treated with an ACE-inhibitor, additional treatment with the ARB candesartan was associated with reduction in the primary endpoint of cardiovascular death or heart failure hospitalizations

www. Clinical trial results.org CHARM Trial CHARM Alternative: Among patients with symptomatic heart failure and an ejection fraction <40% who were ACE-inhibitor intolerant, treatment with the ARB candesartan was associated with reduction in the primary endpoint of cardiovascular death or heart failure hospitalizations CHARM Preserved: Among patients with symptomatic heart failure and an ejection fraction >40%, treatment with the ARB candesartan was associated with a non-significant reduction in the primary endpoint of cardiovascular death or heart failure hospitalizations CHARM Alternative: Among patients with symptomatic heart failure and an ejection fraction <40% who were ACE-inhibitor intolerant, treatment with the ARB candesartan was associated with reduction in the primary endpoint of cardiovascular death or heart failure hospitalizations CHARM Preserved: Among patients with symptomatic heart failure and an ejection fraction >40%, treatment with the ARB candesartan was associated with a non-significant reduction in the primary endpoint of cardiovascular death or heart failure hospitalizations