This trial was three trials in one, but the overall goal of the trial was to see if the addition of candesartan reduced mortality and hospitalizations a broad spectrum of symptomatic heart failure. As mentioned the trial was split into three parallel trials and grouped by ejection fraction and if they were or were not tolerant of an ACE inhibitor. CHARM Added addressed those with a LVEF of 40% or less who were already on an ACE, and yes, an ARB was added to their ACE inhibitor. CHARM Alternative also addressed those with a LVEF of 40% or less, but who were not tolerant of an ACE, using candesartan instead. Lastly, CHARM Preserved addressed those with a LVEF of >40% who were not already on an ACE. The primary endpoint of the overall CHARM Trial, which pooled results of all three individual CHARM Trials was all-cause mortality. The primary outcome of the individual CHARM Trials was the combined endpoint of cardiovascular mortality or heart failure hospitalization.
The three trials were double-blind randomized placebo-controlled trials which, when combined, included 7601 patients who were assigned candesartan or placebo. Median follow up was 37.5 months. The primary outcome -- all-cause mortality was not significantly different between the two groups. Secondary outcomes were 1) the combined endpoint of CV mortality, nonfatal MI, and hospitalization for heart failure; 2) combined all-cause hospitalization and all-cause mortality; 3) combined hospitalization, all-cause mortality, CV mortality, nonfatal MI, and hospitalization for the management of heart failure; 4) resource utilization, safety, and tolerability; and 5) new diabetes. Candesartan was associated with a reduction in cardiovascular mortality as well as CHF hospitalizations. Among the three individual trials, there was a reduction in CV mortality and hospitalization for CHF in the CHARM Added and CHARM Alternative trials, but not the CHARM Preserved Trial.
The overall CHARM Trial: Pfeffer, M. A., Swedberg, K., Granger, C. B., Held, P., McMurray, J. J., Michelson, E. L., ... & CHARM Investigators and Committees. (2003). Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. The Lancet, 362(9386), 759-766.
The overall CHARM Trial PMID: 13678868
The CHARM Added Trial: McMurray, J. J., Östergren, J., Swedberg, K., Granger, C. B., Held, P., Michelson, E. L., ... & CHARM Investigators and Committees. (2003). Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial. The Lancet, 362(9386), 767-771.
The CHARM Added PMID: 13678869
The CHARM Alternative Trial: Granger, C. B., McMurray, J. J., Yusuf, S., Held, P., Michelson, E. L., Olofsson, B., ... & CHARM Investigators and Committees. (2003). 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. The Lancet, 362(9386), 772-776.
The CHARM Alternative PMID: 13678870
The CHARM Preserved Trial: Yusuf, S., Pfeffer, M. A., Swedberg, K., Granger, C. B., Held, P., McMurray, J. J., ... & CHARM Investigators and Committees. (2003). Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. The Lancet, 362(9386), 777-781.
The CHARM Preserved PMID: 13678871
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