The CHARM Program trials demonstrated a significant reduction in cardiovascular death or hospital admission for HF in the candesartan group compared with placebo of 30% (95% CI 19–40%; P < 0.0001) in 2028 patients with symptomatic HFrEF who were not receiving ACE inhibitors due to previous intolerance (Granger et al., 2003; McMurray et al., 2003). Here, ACE is linked to hydrops fetalis.