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.