Initial data supporting the design of the Candesartan in Heart failure--assessment of reduction in mortality and morbidity (CHARM) programme.

Background The therapies developed to treat heart failure over the years have resulted in a significant improvement in clinical outcome. The 1-year mortality following hospital discharge remains unacceptably high, however. Furthermore, a significant number of patients are unable to tolerate angiotensin-converting enzyme (ACE) inhibitors. Clearly, scope remains for the improvement of neurohormonal blockade in patients with heart failure, and there is a particular need for alternative therapies in patients who are unable to tolerate ACE inhibitors. The use of angiotensin II receptor blockers may provide a means of fulfilling these needs. Objectives This paper reviews the studies examining the angiotensin II receptor blocker candesartan in comparison with placebo, in comparison with ACE inhibitors, and in combination with ACE inhibitors. Conclusions Overall the review found candesartan was effective and safe in various clinical settings. These initial data were used to design the Candesartan in Heart failure -Assessment of Reduction in Mortality and morbidity (CHARM) programme. The mechanistic studies performed prior to the CHARM programme supported the rationale to design a large trial examining the effects of candesartan on clinical events.